CClinicalTrials.gg
Sign In
CompletedNCT00809133Updated Mar 14, 2016Results posted

Trial Exploring Afatinib (BIBW 2992) + Paclitaxel (Part A), Afatinib + Paclitaxel + Bevacizumab (Part B), Afatinib + Carboplatin (Part C) and Afatinib+ Paclitaxel +Carboplatin(Part D) in Patients With Advanced Solid Tumours

A Phase 1 interventional study of Paclitaxel and Carboplatin in Neoplasms, sponsored by Boehringer Ingelheim. Completed at 2 sites in United Kingdom. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2016-03-14.

Sponsored by Boehringer Ingelheim · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
83
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

The main purpose of this study is to assess the optimum dose of the following medications when they are given together:

  • BIBW 2992 and paclitaxel (Taxol)
  • BIBW 2992 and paclitaxel and bevacizumab (Avastin)
  • BIBW 2992 and carboplatin
  • BIBW 2992 and paclitaxel and carboplatin The effect of the different drug combinations will also be assessed.
02

Conditions studied

  • Neoplasms
03

In context

Lead sponsor

Boehringer Ingelheim is the lead sponsor of 2,245 studies on the registry; 58 are open to participants now.

Of its 162 completed or terminated interventional studies of FDA-regulated products, 116 (72%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Male or female patients (patients) with a histologically confirmed diagnosis of malignancy that is now advanced, non-resectable and / or metastatic.
  2. Age 18 years old or older.
  3. Life expectancy of at least 3 months.
  4. Written informed consent that is consistent with ICH-GCP guidelines.
  5. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
  6. Patients must have recovered from any previous surgery.
  7. Adequate organ function including the following:
  8. Cardiac left ventricular function with resting ejection fraction greater than or equal to 50%
  9. Absolute neutrophil count of greater than or equal to 1,500/microlitres; greater than 2000/microlitres for carboplatin
  10. Platelets greater than or equal to 100,000/microlitres
  11. Total bilirubin less than or equal to 1.5 mg/dl (\<26 micromol /L, SI unit equivalent).
  12. AST(SGOT)/ALT(SGPT) less than or equal to 2.5 X institutional upper limit of normal.
  13. Creatinine less than or equal to 1.5 mg/dl (less than or equal to 132 micromol per liter, SI unit equivalent).
  14. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) for the duration of trial participation. Female patients with reproductive potential must have a negative serum pregnancy test within 7 days of trial enrolment. Breast feeding mothers will be excluded since these agents may be toxic to infants.

Exclusion criteria

Exclusion criteria:

  1. Active infectious disease
  2. Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol
  3. GI tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease.
  4. Significant cardiovascular disease (a history of congestive heart failure requiring therapy, a need for anti-arrhythmic therapy for a ventricular arrhythmia, unstable angina pectoris or myocardial infarction within 6 months prior to trial entry).
  5. Patients who require full-dose anticoagulation.
  6. Patients not completely recovered from any therapy-related toxicities from previous chemo-, hormone-, immuno-, or radiotherapies to CTC less than or equal to Grade 1. Prior chemotherapy is allowed if completed at least 4 weeks prior to 1st trial treatment (6 weeks for mitomycin C or nitrosoureas) and the patient has recovered from the acute toxicities of that therapy.
  7. Patients with untreated or symptomatic brain metastases. Patients with treated, asymptomatic brain metastases are eligible if there has been no change in brain disease status for at least 8 weeks, no history of cerebral oedema or bleeding in the past 8 weeks and no requirement for steroids or anti-epileptic therapy
  8. Persistent Grade 2 or greater neurotoxicity / neuropathy from any cause.
  9. Patients on immunosuppressant therapy or with known HIV infection.
  10. Treatment with any of the following within 4 weeks of starting trial medication, or during the trial, is not permitted: chemo-, immuno-, radio- (small field palliative radiotherapy is allowed provided this does not represent clear disease progression), biological therapies (including trastuzumab), hormone therapy (excluding LHRH agonists in prostate cancer, or bisphosphonates), or treatment with other investigational drugs.
  11. Participation in another clinical trial within the past 4 weeks before start of therapy or concomitantly with this trial.
  12. Prior treatment with EGFR targeting therapies or treatment with EGFR- or HER2 inhibiting drugs within the past 4 weeks before start of therapy or concomitantly with this trial.
  13. Patients with known or suspected hypersensitivity to any of the trial drugs, their excipients or similar compounds.
  14. Patients unable to comply with the protocol.
  15. Active alcohol or drug abuse.

  16. Patients with known pre-existing interstitial lung disease

    Additional exclusion criteria for patients recruited to cohorts B:

  17. Patients with known or suspected hypersensitivity to bevacizumab, its excipients or Chinese hamster ovary cell products or other recombinant human or humanised antibodies.
  18. Patients with brain metastases (a brain scan is not required unless the patient shows signs and symptoms of brain metastases and a brain scan is performed to rule out the presence of brain metastases).
  19. Patients with intra-abdominal inflammation .
  20. Major surgery within 4 weeks of starting treatment or any wound(s) deemed by the investigator to pose a significant risk to the patient in the event of delayed healing.
  21. Prior treatment with anthracycline and/or prior radiation to the chest wall ( patients in these categories will only be entered into the study where the investigator deems the benefit to the patient to outweigh the risk).

  22. Patients with any of the following conditions: significant hypertension, significant haemoptysis, known brian metastases, thrombotic or haemorrhagic disorders, INR greater than or equal to 1.5 abnormal PTT, therapeutic anti-coagulation, squamous non small cell lung cancer Additional exclusion criteria for patients recruited to cohorts C and D

    • Patients with severe myelosuppression; i.e. absolute neutrophil count less than 2000/microlitres
    • Patients with renal impairment (creatinine clearance less than 60ml per minute by Cockcroft-Gault equation)
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Masking
None (open label)
Enrollment
83 participants (actual)

Study arms

  • Experimental
    Part A

    BIBW2992 + Paclitaxel

    Drug: BIBW 2992 · Drug: Paclitaxel

  • Experimental
    Part B

    BIBW2992 + Paclitaxel + Bevacizumab

    Drug: Paclitaxel · Drug: BIBW2992 · Drug: Bevacizumab

  • Experimental
    Part C

    BIBW2992 + Carboplatin

    Drug: Carboplatin · Drug: BIBW 2992

  • Experimental
    Part D

    BIBW2992 +Paclitaxel + Carboplatin

    Drug: Carboplatin · Drug: Paclitaxel · Drug: BIBW 2992

Interventions

  • DrugPaclitaxel

    Part A and B:80mg/m2 given on Day 1, 8 and 15 of 28 Day cycle.

  • DrugCarboplatin

    AUC6 given on day 1 of 21 day cycle

  • DrugBIBW 2992

    Escalating dose cohorts

  • DrugPaclitaxel

    Part A and B:80mg/m2 given on Day 1, 8 and 15 of 28 Day cycle.

  • DrugBIBW2992

    MTD dose of part A

  • DrugPaclitaxel

    175mg/m2 given on Day 1 of 21 Day cycle

  • DrugCarboplatin

    AUC6 given on day 1 of 21 day cycle

  • DrugBevacizumab

    Escalating dose Cohorts - 5mg / kg, 7.5mg / kg and 10mg / kg given Day 1 and Day 15 of a 28 days cycle

  • DrugBIBW 2992

    Escalating dose cohorts

  • DrugBIBW 2992

    Escalating dose cohorts

06

What researchers measure

Primary outcomes

  1. Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)

    Dose limiting toxicity (DLT) was defined as an Adverse Event (AE) or laboratory abnormality considered as related to study treatment.

    Time frame: Cycle 1: 21 days (part C and D) or 28 days (part A and B)

  2. Maximum Tolerated Dose (MTD)

    The MTD of afatinib in selected combination treatments was defined as the highest dose at which no more than 1 out of 6 patients experienced DLTs during the first treatment cycle, i.e. the highest dose with a DLT incidence ≤17%. The MTD was determined separately for Afatinib in combination with Paclitaxel (part A), Afatinib in combination with Paclitaxel and Bevacizumab (part B), Afatinib and Carboplatin (part C), and Afatinib in combination with Paclitaxel and Carboplatin (part D). In part C, dose escalation was not continued beyond the dose level A40C6, due to safety and pharmacokinetic considerations and upon mutual agreement between the investigators and the sponsor. Formally, no MTD was determined, however a recommended phase II dose was determined and is presented here. 0=not maximum tolerated dose, 1=is maximum tolerated dose Note, the depicted order of treatment groups is driven by dose level, not by the actual dosing steps.

    Time frame: Cycle 1: 21 days (part C and D) or 28 days (part A and B)

Secondary outcomes

  1. Incidence and Intensity of AEs According to the Maximum Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grade

    Incidence and Intensity of AEs (Adverse Events) graded according to the maximum CTCAE (Common Toxicity Criteria for Adverse Events) grade based on the number of patients with AEs with CTCAE Grade 1-5.

    Time frame: From first drug administration until the end of treatment cycle 1; 21 days (part C and D) or 28 days (part A and B)

  2. Part A: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State on Day 15

    Area under the concentration-time curve of Afatinib in plasma at steady state.

    Time frame: Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 and 24:00.

  3. Part A: Afatinib Cmax,ss on Day 15

    Maximum measured concentration of Afatinib in plasma at steady state.

    Time frame: Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 and 24:00.

  4. Part A: AUC0-24: Area Under the Concentration-Time Curve of Paclitaxel in Plasma Over the Time Interval From Zero Extrapolated to 24 Hours on Day 1 and Day 15

    AUC0-24: Area under the concentration-time curve of Paclitaxel in plasma over the time interval from zero extrapolated to 24 hours.

    Time frame: Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.

  5. Part A: Paclitaxel Cmax on Day 1 and Day 15

    Maximum measured concentration of Paclitaxel in plasma.

    Time frame: Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.

  6. Part B: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State on Day 15

    Area under the concentration-time curve of Afatinib in plasma at steady state.

    Time frame: Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. There were no analyzable patients for Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab.

  7. Part B: Afatinib Cmax,ss on Day 15

    Maximum measured concentration of Afatinib in plasma at steady state.

    Time frame: Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 and 24:00.

  8. Part B: Area Under the Concentration-Time Curve of Paclitaxel in Plasma Over the Time Interval From 0 Extrapolated Upto 24 Hours on Day 1 and Day 15

    AUC0-24: Area under the concentration-time curve of Paclitaxel in plasma over the time interval from zero extrapolated to 24 hours.

    Time frame: Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.

  9. Part B: Paclitaxel Cmax on Day 1 and Day 15

    Maximum measured concentration of Paclitaxel in plasma.

    Time frame: Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.

  10. Part B: Bevacizumab Plasma Concentration

    Bevacizumab plasma concentration after infusion of Bevacizumab 5mg/kg after end of 1st and 2nd infusion in Cycle 1.

    Time frame: Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.

  11. Part C: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State in Cycle 2

    AUCt,ss: Area under the concentration-time curve of Afatinib in plasma at steady state.

    Time frame: Cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.

  12. Part C: Afatinib Cmax,ss in Cycle 2

    Maximum measured concentration of Afatinib in plasma at steady state.

    Time frame: Cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.

  13. Part C: Area Under the Concentration-Time Curve of Carboplatin in Plasma Over the Time Interval From 0 Extrapolated Upto 24 Hours in Cycle 1 and Cycle 2

    AUC0-24: Area under the concentration-time curve of Carboplatin in plasma over the time interval from zero extrapolated to 24 hours.

    Time frame: Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 24:00.

  14. Part C: Carboplatin Cmax in Cycle 1 and Cycle 2

    Maximum measured concentration of Carboplatin in plasma.

    Time frame: Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 24:00

  15. Part D: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State.

    AUCt,ss: Area under the concentration-time curve of Afatinib at steady state.

    Time frame: Cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.

  16. Part D: Afatinib Cmax,ss

    Maximum measured concentration of Afatinib in plasma at steady state.

    Time frame: Cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.

  17. Part D: Area Under the Concentration-Time Curve of Paclitaxel in Plasma Over the Time Interval From 0 Extrapolated Upto 23 Hours in Cycle 1 and Cycle 2

    AUC0-23: Area under the concentration-time curve of Paclitaxel in plasma over the time interval from zero extrapolated to 23 hours.

    Time frame: Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 23:00.

  18. Part D: Paclitaxel Cmax in Cycle 1 and 2

    Maximum measured concentration of Paclitaxel in plasma.

    Time frame: Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00

  19. Part D: Area Under the Concentration-Time Curve of Carboplatin in Plasma Over the Time Interval From 0 Extrapolated Upto 24 Hours in Cycle 1 and Cycle 2

    AUC0-24: Area under the concentration-time curve of Carboplatin in plasma over the time interval from zero extrapolated to 24 hours.

    Time frame: Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00

  20. Part D: Carboplatin Cmax in Cycle 1 and 2

    Maximum measured concentration of Carboplatin in plasma.

    Time frame: Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.

  21. Objective Tumour Response (Unconfirmed)

    Number of subjects with objective tumour response (unconfirmed). Objective Response (OR) was defined as Complete Response (CR) or Partial Response (PR).

    Time frame: From first drug administration until the last trial drug administration, up to 1156 days.

  22. Objective Tumour Response (Confirmed)

    Number of subjects with confirmed objective tumour response. Objective Response (OR) was defined as Complete Response (CR) or Partial Response (PR). Objective response was to be confirmed by a second tumour assessment at least 4 weeks after the assessment of CR or PR.

    Time frame: From first drug administration until the last trial drug administration, up to 1156 days.

07

Results

Posted Mar 14, 2016

Participant flow

This was a phase I open label trial of continuous dosing with BIBW 2992 (Afatinib) combined with Paclitaxel and BIBW 2992 combined with Paclitaxel and Bevacizumab, BIBW 2992 combined with Carboplatin and BIBW 2992 combined with Paclitaxel and Carboplatin in patients with advanced solid tumours.

Participant flow — Overall Study
MilestonePart A: A20P80 (Afatinib + Paclitaxel)Part A: A40P80 (Afatinib + Paclitaxel)Part A: A50P80 (Afatinib + Paclitaxel)Part B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)Part C: A20C6 (Afatinib + Carboplatin)Part C: A40C6 (Afatinib + Carboplatin)Part D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)
Started37635768396857
Completed00000000000000
Not completed37635768396857
Withdrew: Progressive disease25534133395754
Withdrew: Dose limiting toxicity (dlt)00000111000002
Withdrew: Other adverse event11100324001101
Withdrew: Lost to follow-up00000100000000
Withdrew: Consent withdrawn00001000000000
Withdrew: Other not mentioned above01000100000000

Outcome measures

PrimaryNumber of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)

Dose limiting toxicity (DLT) was defined as an Adverse Event (AE) or laboratory abnormality considered as related to study treatment.

Time frame:
Cycle 1: 21 days (part C and D) or 28 days (part A and B)
Reported as:
Number · Participants
Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)
ParticipantsPart A: A20P80 (Afatinib + Paclitaxel)Part A: A40P80 (Afatinib + Paclitaxel)Part A: A50P80 (Afatinib + Paclitaxel)Part B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)Part C: A20C6 (Afatinib + Carboplatin)Part C: A40C6 (Afatinib + Carboplatin)Part D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)
Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)00202211010222
PrimaryMaximum Tolerated Dose (MTD)

The MTD of afatinib in selected combination treatments was defined as the highest dose at which no more than 1 out of 6 patients experienced DLTs during the first treatment cycle, i.e. the highest dose with a DLT incidence ≤17%. The MTD was determined separately for Afatinib in combination with Paclitaxel (part A), Afatinib in combination with Paclitaxel and Bevacizumab (part B), Afatinib and Carboplatin (part C), and Afatinib in combination with Paclitaxel and Carboplatin (part D). In part C, dose escalation was not continued beyond the dose level A40C6, due to safety and pharmacokinetic considerations and upon mutual agreement between the investigators and the sponsor. Formally, no MTD was determined, however a recommended phase II dose was determined and is presented here. 0=not maximum tolerated dose, 1=is maximum tolerated dose Note, the depicted order of treatment groups is driven by dose level, not by the actual dosing steps.

Time frame:
Cycle 1: 21 days (part C and D) or 28 days (part A and B)
Reported as:
Number · Units on a scale
Maximum Tolerated Dose (MTD)
Units on a scalePart A: A20P80 (Afatinib + Paclitaxel)Part A: A40P80 (Afatinib + Paclitaxel)Part A: A50P80 (Afatinib + Paclitaxel)Part B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)Part C: A20C6 (Afatinib + Carboplatin)Part C: A40C6 (Afatinib + Carboplatin)Part D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)
Maximum Tolerated Dose (MTD)01000001011000
SecondaryIncidence and Intensity of AEs According to the Maximum Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grade

Incidence and Intensity of AEs (Adverse Events) graded according to the maximum CTCAE (Common Toxicity Criteria for Adverse Events) grade based on the number of patients with AEs with CTCAE Grade 1-5.

Time frame:
From first drug administration until the end of treatment cycle 1; 21 days (part C and D) or 28 days (part A and B)
Reported as:
Number · Participants
Incidence and Intensity of AEs According to the Maximum Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grade
ParticipantsPart A: A20P80 (Afatinib + Paclitaxel)Part A: A40P80 (Afatinib + Paclitaxel)Part A: A50P80 (Afatinib + Paclitaxel)Part B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)Part C: A20C6 (Afatinib + Carboplatin)Part C: A40C6 (Afatinib + Carboplatin)Part D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)
Grade 100000000000000
Grade 222312103021012
Grade 305322364143643
Grade 410000100131202
Grade 500001201101000
SecondaryPart A: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State on Day 15

Area under the concentration-time curve of Afatinib in plasma at steady state.

Time frame:
Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 and 24:00.
Reported as:
Geometric mean · ng*h/mL
Part A: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State on Day 15
ng*h/mLPart A: A20P80 (Afatinib + Paclitaxel)Part A: A40P80 (Afatinib + Paclitaxel)Part A: A50P80 (Afatinib + Paclitaxel)
Part A: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State on Day 15250 ± 9.63813 ± 58.4939 ± 60.0
SecondaryPart A: Afatinib Cmax,ss on Day 15

Maximum measured concentration of Afatinib in plasma at steady state.

Time frame:
Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 and 24:00.
Reported as:
Geometric mean · ng/mL
Part A: Afatinib Cmax,ss on Day 15
ng/mLPart A: A20P80 (Afatinib + Paclitaxel)Part A: A40P80 (Afatinib + Paclitaxel)Part A: A50P80 (Afatinib + Paclitaxel)
Part A: Afatinib Cmax,ss on Day 1512.3 ± 15.546.0 ± 61.963.5 ± 74.6
SecondaryPart A: AUC0-24: Area Under the Concentration-Time Curve of Paclitaxel in Plasma Over the Time Interval From Zero Extrapolated to 24 Hours on Day 1 and Day 15

AUC0-24: Area under the concentration-time curve of Paclitaxel in plasma over the time interval from zero extrapolated to 24 hours.

Time frame:
Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.
Reported as:
Geometric mean · ng*h/mL
Part A: AUC0-24: Area Under the Concentration-Time Curve of Paclitaxel in Plasma Over the Time Interval From Zero Extrapolated to 24 Hours on Day 1 and Day 15
ng*h/mLPart A: A20P80 (Afatinib + Paclitaxel)Part A: A40P80 (Afatinib + Paclitaxel)Part A: A50P80 (Afatinib + Paclitaxel)
Day 1 (N=3, 6, 5)1970 ± 52.23730 ± 28.53260 ± 30.1
Day 15 (N=3, 6, 5)3560 ± 12.63170 ± 67.73950 ± 51.8
SecondaryPart A: Paclitaxel Cmax on Day 1 and Day 15

Maximum measured concentration of Paclitaxel in plasma.

Time frame:
Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.
Reported as:
Geometric mean · ng/mL
Part A: Paclitaxel Cmax on Day 1 and Day 15
ng/mLPart A: A20P80 (Afatinib + Paclitaxel)Part A: A40P80 (Afatinib + Paclitaxel)Part A: A50P80 (Afatinib + Paclitaxel)
Day 1428 ± 3872090 ± 37.71480 ± 63.1
Day 151880 ± 42.21590 ± 82.22120 ± 68.2
SecondaryPart B: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State on Day 15

Area under the concentration-time curve of Afatinib in plasma at steady state.

Time frame:
Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. There were no analyzable patients for Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab.
Reported as:
Geometric mean · ng*h/mL
Part B: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State on Day 15
ng*h/mLPart B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)
Part B: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State on Day 15312 ± 10.3—829 ± 56.3336 ± 60.1142 ± 132
SecondaryPart B: Afatinib Cmax,ss on Day 15

Maximum measured concentration of Afatinib in plasma at steady state.

Time frame:
Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 and 24:00.
Reported as:
Geometric mean · ng/mL
Part B: Afatinib Cmax,ss on Day 15
ng/mLPart B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)
Part B: Afatinib Cmax,ss on Day 1520.4 ± 16.521.4 ± 37.850.4 ± 52.922.8 ± 78.39.75 ± 214
SecondaryPart B: Area Under the Concentration-Time Curve of Paclitaxel in Plasma Over the Time Interval From 0 Extrapolated Upto 24 Hours on Day 1 and Day 15

AUC0-24: Area under the concentration-time curve of Paclitaxel in plasma over the time interval from zero extrapolated to 24 hours.

Time frame:
Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.
Reported as:
Geometric mean · ng*h/mL
Part B: Area Under the Concentration-Time Curve of Paclitaxel in Plasma Over the Time Interval From 0 Extrapolated Upto 24 Hours on Day 1 and Day 15
ng*h/mLPart B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)
Day 13760 ± 53.03330 ± 20.85090 ± 38.63810 ± 32.93540 ± 40.3
Day 15NA ± NANA ± NA4060 ± 31.85290 ± 45.6NA ± NA
SecondaryPart B: Paclitaxel Cmax on Day 1 and Day 15

Maximum measured concentration of Paclitaxel in plasma.

Time frame:
Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.
Reported as:
Geometric mean · ng/mL
Part B: Paclitaxel Cmax on Day 1 and Day 15
ng/mLPart B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)
Day 11800 ± 1121700 ± 24.22950 ± 26.61920 ± 38.41750 ± 63.1
Day 151490 ± 19.41550 ± 47.41620 ± 39.02730 ± 48.42120 ± 37.3
SecondaryPart B: Bevacizumab Plasma Concentration

Bevacizumab plasma concentration after infusion of Bevacizumab 5mg/kg after end of 1st and 2nd infusion in Cycle 1.

Time frame:
Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.
Reported as:
Median · μg/mL
Part B: Bevacizumab Plasma Concentration
μg/mLPart B: End of 1st Infusion of Cycle 1Part B: End of 2nd Infusion of Cycle 1
Part B: Bevacizumab Plasma Concentration119 ± 53.0154 ± 20.8
SecondaryPart C: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State in Cycle 2

AUCt,ss: Area under the concentration-time curve of Afatinib in plasma at steady state.

Time frame:
Cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.
Reported as:
Geometric mean · ng*h/mL
Part C: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State in Cycle 2
ng*h/mLPart C: A20C6 (Afatinib + Carboplatin)Part C: A40C6 (Afatinib + Carboplatin)
Part C: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State in Cycle 2511 ± 1.87465 ± 91.8
SecondaryPart C: Afatinib Cmax,ss in Cycle 2

Maximum measured concentration of Afatinib in plasma at steady state.

Time frame:
Cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.
Reported as:
Geometric mean · ng/mL
Part C: Afatinib Cmax,ss in Cycle 2
ng/mLPart C: A20C6 (Afatinib + Carboplatin)Part C: A40C6 (Afatinib + Carboplatin)
Part C: Afatinib Cmax,ss in Cycle 241.7 ± 28.044.2 ± 9.76
SecondaryPart C: Area Under the Concentration-Time Curve of Carboplatin in Plasma Over the Time Interval From 0 Extrapolated Upto 24 Hours in Cycle 1 and Cycle 2

AUC0-24: Area under the concentration-time curve of Carboplatin in plasma over the time interval from zero extrapolated to 24 hours.

Time frame:
Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 24:00.
Reported as:
Geometric mean · ng*h/mL
Part C: Area Under the Concentration-Time Curve of Carboplatin in Plasma Over the Time Interval From 0 Extrapolated Upto 24 Hours in Cycle 1 and Cycle 2
ng*h/mLPart C: A20C6 (Afatinib + Carboplatin)Part C: A40C6 (Afatinib + Carboplatin)
Cycle 1 (N=3, 9)77500 ± 5.4776800 ± 16.9
Cycle 2 (N=3, 6)77600 ± 7.3675700 ± 23.6
SecondaryPart C: Carboplatin Cmax in Cycle 1 and Cycle 2

Maximum measured concentration of Carboplatin in plasma.

Time frame:
Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 24:00
Reported as:
Geometric mean · ng/mL
Part C: Carboplatin Cmax in Cycle 1 and Cycle 2
ng/mLPart C: A20C6 (Afatinib + Carboplatin)Part C: A40C6 (Afatinib + Carboplatin)
Cycle 1 (N=3, 9)15100 ± 19.321100 ± 31.0
Cycle 2 (N=3, 6)15200 ± 18.119600 ± 26.8
SecondaryPart D: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State.

AUCt,ss: Area under the concentration-time curve of Afatinib at steady state.

Time frame:
Cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.
Reported as:
Geometric mean · ng*h/mL
Part D: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State.
ng*h/mLPart D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)
Part D: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State.326 ± 60.4454 ± 61.7506 ± 14.9119 ± 0.110
SecondaryPart D: Afatinib Cmax,ss

Maximum measured concentration of Afatinib in plasma at steady state.

Time frame:
Cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.
Reported as:
Geometric mean · ng/mL
Part D: Afatinib Cmax,ss
ng/mLPart D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)
Part D: Afatinib Cmax,ss18.3 ± 52.627.3 ± 48.428.1 ± 4.276.73 ± 7.99
SecondaryPart D: Area Under the Concentration-Time Curve of Paclitaxel in Plasma Over the Time Interval From 0 Extrapolated Upto 23 Hours in Cycle 1 and Cycle 2

AUC0-23: Area under the concentration-time curve of Paclitaxel in plasma over the time interval from zero extrapolated to 23 hours.

Time frame:
Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 23:00.
Reported as:
Geometric mean · ng*h/mL
Part D: Area Under the Concentration-Time Curve of Paclitaxel in Plasma Over the Time Interval From 0 Extrapolated Upto 23 Hours in Cycle 1 and Cycle 2
ng*h/mLPart D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)
Cycle 1 (N=5, 7, 5, 6)10400 ± 21.813000 ± 24.99220 ± 43.810200 ± 19.9
Cycle 2 (N=8, 5, 2, 4)10700 ± 32.214800 ± 9.7811900 ± 41.49270 ± 53.2
SecondaryPart D: Paclitaxel Cmax in Cycle 1 and 2

Maximum measured concentration of Paclitaxel in plasma.

Time frame:
Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00
Reported as:
Geometric mean · ng/mL
Part D: Paclitaxel Cmax in Cycle 1 and 2
ng/mLPart D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)
Cycle 1 (N=5, 7, 5, 6)3710 ± 23.44230 ± 33.72570 ± 36.63020 ± 29.1
Cycle 2 (N=8, 5, 2, 4)3620 ± 50.94850 ± 20.73290 ± 52.72590 ± 92.3
SecondaryPart D: Area Under the Concentration-Time Curve of Carboplatin in Plasma Over the Time Interval From 0 Extrapolated Upto 24 Hours in Cycle 1 and Cycle 2

AUC0-24: Area under the concentration-time curve of Carboplatin in plasma over the time interval from zero extrapolated to 24 hours.

Time frame:
Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00
Reported as:
Geometric mean · ng*h/mL
Part D: Area Under the Concentration-Time Curve of Carboplatin in Plasma Over the Time Interval From 0 Extrapolated Upto 24 Hours in Cycle 1 and Cycle 2
ng*h/mLPart D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)
Cycle 1 (N=5, 7, 5, 7)69700 ± 12.464900 ± 29.668700 ± 17.281000 ± 15.3
Cycle 2 (N=8, 5, 2, 5)65400 ± 20.974800 ± 15.172100 ± 27.590300 ± 15.7
SecondaryPart D: Carboplatin Cmax in Cycle 1 and 2

Maximum measured concentration of Carboplatin in plasma.

Time frame:
Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.
Reported as:
Geometric mean · ng/mL
Part D: Carboplatin Cmax in Cycle 1 and 2
ng/mLPart D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)
Cycle 1 (N=5, 7, 5, 7)16200 ± 22.917900 ± 17.615600 ± 28.018500 ± 24.3
Cycle 2 (N=8, 5, 2, 5)17800 ± 15.818600 ± 24.212800 ± 021500 ± 14.3
SecondaryObjective Tumour Response (Unconfirmed)

Number of subjects with objective tumour response (unconfirmed). Objective Response (OR) was defined as Complete Response (CR) or Partial Response (PR).

Time frame:
From first drug administration until the last trial drug administration, up to 1156 days.
Reported as:
Number · Participants
Objective Tumour Response (Unconfirmed)
ParticipantsPart A: A20P80 (Afatinib + Paclitaxel)Part A: A40P80 (Afatinib + Paclitaxel)Part A: A50P80 (Afatinib + Paclitaxel)Part B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)Part C: A20C6 (Afatinib + Carboplatin)Part C: A40C6 (Afatinib + Carboplatin)Part D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)
Objective response: No33534557274626
Objective response: Yes04101211122231
SecondaryObjective Tumour Response (Confirmed)

Number of subjects with confirmed objective tumour response. Objective Response (OR) was defined as Complete Response (CR) or Partial Response (PR). Objective response was to be confirmed by a second tumour assessment at least 4 weeks after the assessment of CR or PR.

Time frame:
From first drug administration until the last trial drug administration, up to 1156 days.
Reported as:
Number · Participants
Objective Tumour Response (Confirmed)
ParticipantsPart A: A20P80 (Afatinib + Paclitaxel)Part A: A40P80 (Afatinib + Paclitaxel)Part A: A50P80 (Afatinib + Paclitaxel)Part B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)Part C: A20C6 (Afatinib + Carboplatin)Part C: A40C6 (Afatinib + Carboplatin)Part D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)
Objective response: No33535558274737
Objective response: Yes04100210122120

Adverse events

Collected over From first drug administration until 21 days (part C and D) or 28 days (part A and B) after the last trial drug administration in the last treatment cycle, up to 1184 days.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Part A: A20P80 (Afatinib + Paclitaxel)—2/3 (66.7%)3/3 (100%)
Part A: A40P80 (Afatinib + Paclitaxel)—5/7 (71.4%)7/7 (100%)
Part A: A50P80 (Afatinib + Paclitaxel)—3/6 (50%)6/6 (100%)
Part B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)—1/3 (33.3%)3/3 (100%)
Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab)—4/5 (80%)5/5 (100%)
Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)—5/7 (71.4%)7/7 (100%)
Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)—6/6 (100%)6/6 (100%)
Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)—5/8 (62.5%)8/8 (100%)
Part C: A20C6 (Afatinib + Carboplatin)—3/3 (100%)3/3 (100%)
Part C: A40C6 (Afatinib + Carboplatin)—3/9 (33.3%)9/9 (100%)
Part D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)—3/6 (50%)6/6 (100%)
Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)—5/8 (62.5%)8/8 (100%)
Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)—4/5 (80%)5/5 (100%)
Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)—4/7 (57.1%)7/7 (100%)
Most frequent serious events
Showing 10 of 79
Most frequent serious events
EventPart A: A20P80 (Afatinib + Paclitaxel)Part A: A40P80 (Afatinib + Paclitaxel)Part A: A50P80 (Afatinib + Paclitaxel)Part B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)Part C: A20C6 (Afatinib + Carboplatin)Part C: A40C6 (Afatinib + Carboplatin)Part D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)
Disease progressionGeneral disorders0/30/70/60/30/50/70/60/82/30/90/60/81/50/7
DiarrhoeaGastrointestinal disorders0/30/70/60/31/51/72/61/80/30/90/60/81/51/7
Mycobacterial infectionInfections and infestations0/30/70/61/30/50/70/60/80/30/90/60/80/50/7
PneumoniaInfections and infestations0/30/70/60/30/50/70/60/81/30/90/60/80/50/7
Respiratory tract infection bacterialInfections and infestations0/30/70/61/30/50/70/60/80/30/90/60/80/50/7
Urinary tract infectionInfections and infestations0/30/70/60/31/50/70/60/81/30/90/60/80/50/7
Vascular pseudoaneurysmInjury, poisoning and procedural complications0/30/70/61/30/50/70/60/80/30/90/60/80/50/7
Metastases to central nervous systemNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/30/70/60/31/50/71/60/81/30/91/60/80/50/7
PresyncopeNervous system disorders1/30/70/60/30/50/70/60/80/30/90/60/80/50/7
PneumothoraxRespiratory, thoracic and mediastinal disorders1/30/70/60/30/50/70/60/80/30/90/60/80/51/7
Most frequent other events
Showing 10 of 307
Most frequent other events
EventPart A: A20P80 (Afatinib + Paclitaxel)Part A: A40P80 (Afatinib + Paclitaxel)Part A: A50P80 (Afatinib + Paclitaxel)Part B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)Part C: A20C6 (Afatinib + Carboplatin)Part C: A40C6 (Afatinib + Carboplatin)Part D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)
ConstipationGastrointestinal disorders1/32/72/63/30/53/74/63/81/32/93/64/83/52/7
DiarrhoeaGastrointestinal disorders2/37/76/63/34/56/74/67/81/36/96/66/85/55/7
NauseaGastrointestinal disorders1/33/72/61/35/52/74/65/81/36/92/63/83/53/7
FatigueGeneral disorders3/35/75/63/35/56/74/66/83/37/95/65/85/56/7
PyrexiaGeneral disorders3/34/71/61/32/50/72/61/81/30/90/61/80/50/7
DyspnoeaRespiratory, thoracic and mediastinal disorders2/32/71/63/31/52/71/61/80/32/90/63/80/52/7
AlopeciaSkin and subcutaneous tissue disorders3/32/71/61/33/52/74/64/80/30/93/62/83/55/7
RashSkin and subcutaneous tissue disorders1/36/75/63/34/54/73/66/82/32/92/66/85/54/7
NeutropeniaBlood and lymphatic system disorders0/31/71/60/30/50/72/62/80/34/95/65/81/53/7
Dry skinSkin and subcutaneous tissue disorders2/34/72/60/34/53/70/61/80/32/92/63/81/53/7

Baseline characteristics

Treated Set: Patients who received at least 1 dose of study treatment were included in the treated set.

Age, Continuous
Age, Continuous(Years)Part A: A20P80 (Afatinib + Paclitaxel)Part A: A40P80 (Afatinib + Paclitaxel)Part A: A50P80 (Afatinib + Paclitaxel)Part B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)Part C: A20C6 (Afatinib + Carboplatin)Part C: A40C6 (Afatinib + Carboplatin)Part D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)Total
Mean56.3 ± 12.953.6 ± 11.256.2 ± 10.546.0 ± 11.159.0 ± 6.852.3 ± 10.455.0 ± 20.556.6 ± 9.073.3 ± 8.354.4 ± 14.752.0 ± 9.853.1 ± 14.262.4 ± 11.164.6 ± 8.656.3 ± 12.3
Sex: Female, Male
Sex: Female, Male(Participants)Part A: A20P80 (Afatinib + Paclitaxel)Part A: A40P80 (Afatinib + Paclitaxel)Part A: A50P80 (Afatinib + Paclitaxel)Part B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)Part C: A20C6 (Afatinib + Carboplatin)Part C: A40C6 (Afatinib + Carboplatin)Part D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)Total
Female2353345204371244
Male1410231635314539
08

Study locations

2 sites
  • 1200.12.4402 Boehringer Ingelheim Investigational Site
    London, United Kingdom
  • 1200.12.4401 Boehringer Ingelheim Investigational Site
    Sutton, United Kingdom
09

References and documents

Publications

  • O'Brien MER, Sarker D, Bhosle J, Thillai K, Yap TA, Uttenreuther-Fischer M, Pemberton K, Jin X, Wiebe S, de Bono J, Spicer J. A phase I study to assess afatinib in combination with carboplatin or with carboplatin plus paclitaxel in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2018 Nov;82(5):757-766. doi: 10.1007/s00280-018-3661-1. Epub 2018 Aug 7. PubMed 30088048 ↗
  • Suder A, Ang JE, Kyle F, Harris D, Rudman S, Kristeleit R, Solca F, Uttenreuther-Fischer M, Pemberton K, Pelling K, Schnell D, de Bono J, Spicer J. A phase I study of daily afatinib, an irreversible ErbB family blocker, in combination with weekly paclitaxel in patients with advanced solid tumours. Eur J Cancer. 2015 Nov;51(16):2275-84. doi: 10.1016/j.ejca.2015.07.041. Epub 2015 Aug 18. PubMed 26296295 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 14, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00809133
Lead sponsor
Boehringer Ingelheim
Responsible party
Sponsor
First posted
Dec 17, 2008
Start date
May 2007
Primary completion
Feb 2015
Completion
Feb 2015
Results posted
Mar 14, 2016
Last update
Mar 14, 2016

Study contacts

Boehringer Ingelheim
study chair · Boehringer Ingelheim
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Feb 2016. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies from this sponsor

Boehringer Ingelheim

Start the discussion