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CompletedNCT01567163Updated Oct 16, 2014Results posted

A Study of Ramucirumab and Docetaxel in Participants With Solid Tumors

A Phase 2 interventional study of Ramucirumab and Docetaxel in Malignant Solid Tumor, sponsored by Eli Lilly and Company. Completed at 6 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-10-16.

Sponsored by Eli Lilly and Company · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
22
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this study is to assess the effect of concomitant ramucirumab on the pharmacokinetics of docetaxel in participants with advanced malignant solid tumors.

Participants who do not complete both Cycle 1, Day 1, and Cycle 2, Day 1 according to schedule will be replaced for the purpose of analysis; these participants may continue to receive study therapy. No dose reductions, delayed or missed doses are allowed during Cycles 1 and 2.

02

Conditions studied

  • Malignant Solid Tumor

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Keywords

  • Advanced Malignant Solid Tumors
03

In context

Neoplasms

9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.

This study's enrollment of 22 is below the median of 50 across 7,253 interventional studies indexed under Neoplasms.

Browse Neoplasms studies →

Lead sponsor

Eli Lilly and Company is the lead sponsor of 2,048 studies on the registry; 140 are open to participants now.

Of its 521 completed or terminated interventional studies of FDA-regulated products, 341 (65%) 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

  • Participant has histologic or cytologic documentation of a malignant solid tumor
  • Participant has an advanced solid tumor that is resistant to standard therapy or for which no standard therapy is available
  • Participant has had 0-1 prior taxane-containing treatment regimens (including taxane monotherapy), which must have been completed at least 6 months before the first dose of study medication. Prior bevacizumab is allowed.
  • Participant has resolution to Grade ≤ 1 (except where otherwise stated in this eligibility criteria) by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v 4.0) of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy
  • Participant has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2
  • Participant has adequate hematologic function (absolute neutrophil count [ANC] ≥ 1500 cells/liter (cells/L), hemoglobin ≥ 10 grams/deciliter (g/dL), and platelet count ≥ 100,000 cells/microliter (cells/mcL)]. Blood transfusion is allowed but must be completed 48 hours before study drug administration.
  • Participant has adequate hepatic function (bilirubin ≤ 1.5 times the upper limit of normal [x ULN], aspartate transaminase [AST] and alanine transaminase [ALT] ≤ 1.5 x ULN)
  • Participant has serum creatinine ≤ 1.5 x ULN. If serum creatinine > 1.5 x ULN, the calculated creatinine clearance [CrCl] should be ≥ 40 milliliters/minute (mL/min)
  • Participant's urinary protein is \<2+ on dipstick or routine urinalysis (UA) at study entry
  • Participant must have adequate coagulation function as defined by an international normalized ratio (INR) of ≤ 1.5 and a partial thromboplastin time (PTT) or an activated PTT (aPTT) ≤ 1.5 x ULN
  • Women with childbearing potential must have a negative serum or urine pregnancy test. Eligible participants of reproductive potential (both sexes) agree to use adequate method of contraception during the study period and for 12 weeks after the last dose of study medication.

Exclusion criteria

Exclusion Criteria:

  • Has a known allergy or hypersensitivity to any of the treatment components
  • Are currently enrolled in, or discontinued within the last 14 days from, a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
  • Has received a therapeutic monoclonal antibody within 42 days prior to first dose of study medication
  • Has received radiotherapy within 14 days prior to first dose of study medication
  • Has received cytotoxic chemotherapy within 21 days prior to first dose of study medication
  • Is receiving concurrent treatment with another anticancer therapy, including chemotherapy, immunotherapy, hormonal therapy (except for androgen deprivation therapy for prostate cancer), radiation therapy, chemoembolization, targeted or other investigational anticancer therapy
  • Is receiving chronic therapy with nonsteroidal anti-inflammatory agents or other antiplatelet agents. (Aspirin use at doses up to 325 milligrams/day (mg/day) and analgesic agents with no or low bleeding risk are permitted.)
  • Has a history of uncontrolled hereditary or acquired bleeding or thromboembolic disorders
  • Has experienced any arterial thromboembolic event, including myocardial infarction (MI), unstable angina, stroke or transient ischemic attack (TIA), within 6 months prior to first dose of study medication
  • Has a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism during the 3 months prior to first dose of study medication
  • Has experienced a Grade 3 or 4 hemorrhagic event within 3 months prior to first dose of study medication
  • Has experienced peripheral neuropathy ≥ Grade 2 at any time prior to study entry
  • Has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection, Crohn's disease, ulcerative colitis, or chronic diarrhea
  • History of gastrointestinal perforation and/or fistulae within 6 months prior to randomization
  • Has an ongoing or active infection requiring treatment with intravenous antibiotics
  • Has a serious or nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to first dose of study medication
  • Has uncontrolled hypertension despite standard medical management
  • Has symptomatic congestive heart failure, symptomatic or poorly controlled cardiac arrhythmia, or any other serious, uncontrolled medical disorders, which in the opinion of the investigator would make the participant ineligible for participation in the study
  • Has known brain or leptomeningeal metastases
  • Has known positive status for human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome-related illness
  • Has known active drug or alcohol abuse
  • Has pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen
  • Has had major surgery within 28 days prior to first dose of study medication or subcutaneous venous access device implantation within 7 days prior to first dose of study medication
  • Has an elective or planned major surgery during the course of the trial
  • If the primary cancer is non-small-cell lung cancer (NSCLC), there is radiographic evidence of intratumor cavitation, major blood vessel invasion or encasement by cancer, or proximity of cancer to major airways
  • Has received prior ramucirumab (IMC-1121B) therapy
  • Is receiving concomitant therapy with clinically relevant inhibitors or inducers of cytochrome P450 3A4 and 3A5 and/or isoenzymes
  • Has cirrhosis at a level of Child-Pugh B (or worse), or cirrhosis and a history of hepatic encephalopathy, or ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
22 participants (actual)

Study arms

  • Experimental
    ramucirumab (IMC-1121B) and docetaxel

    Cycle 1: docetaxel administered on Day 1 of 3-week cycle Cycle 2: ramucirumab and docetaxel administered on Day 1 of 3-week cycle Cycle 3 and beyond: ramucirumab and docetaxel administered on Day 1 of each 3-week cycle Extension Phase: ramucirumab and docetaxel administered on Day 1 of each 3-week cycle

    Biological: Ramucirumab · Drug: Docetaxel

Interventions

  • BiologicalRamucirumab

    ramucirumab 10 milligrams/kilogram (mg/kg) intravenous infusion, administered on Day 1 of 3-week cycle

    Also known as: IMC-1121B, LY3009806

  • DrugDocetaxel

    docetaxel 75 milligrams/square meter (mg/m\^2) intravenous infusion administered on Day 1 of each 3-week cycle

06

What researchers measure

Primary outcomes

  1. Pharmacokinetics: Dose-Normalized Area Under the Concentration Versus Time Curve of Docetaxel From Time Zero to Infinity [AUC(0-∞)] Following a Single Dose in Cycle 1

    Time frame: Cycle 1: 0, 1, 1.5, 2, 3, 5, 7, 24, 48 and 72 hours post docetaxel infusion

  2. Pharmacokinetics: Dose-Normalized Area Under the Concentration Versus Time Curve of Docetaxel From Time Zero to Infinity [AUC(0-∞)] Following a Single Dose in Cycle 2

    Time frame: Cycle 2: 0, 1, 1.5, 2, 3, 5, 7, 24, 48 and 72 hours post docetaxel infusion

  3. Pharmacokinetics: Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Docetaxel in Cycle 1

    Time frame: Cycle 1: 0, 1, 1.5, 2, 3, 5, 7, 24, 48, and 72 hours post docetaxel infusion

  4. Pharmacokinetics: Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Docetaxel in Cycle 2

    Time frame: Cycle 2: 0, 1, 1.5, 2, 3, 5, 7, 24, 48 and 72 hours post docetaxel infusion

Secondary outcomes

  1. Number of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies

    Participants with treatment-emergent anti-ramucirumab antibodies were participants with a 4-fold increase (2 dilution increase) in immunogenicity titer over baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20).

    Time frame: Cycle 1, Day 1 through Cycle 2, Day 1 and 30 days after last dose of study drug

  2. Pharmacokinetics: Area Under the Concentration Versus Time Curve of Ramucirumab From Time Zero to Infinity [AUC(0-∞)] in the Presence of Docetaxel

    Time frame: Cycle 2: 1 hour prior to ramucirumab infusion, 0, 1, 2, 2.5, 3, 4, 6, 8, 25, 49, 73, 169, 265 and 337 hours post ramucirumab infusion

  3. Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Ramucirumab in the Presence of Docetaxel

    Time frame: Cycle 2: 1 hour prior to ramucirumab infusion, 0, 1, 2, 2.5, 3, 4, 6, 8, 25, 49, 73, 169, 265 and 337 hours post ramucirumab infusion

07

Results

Posted Jun 18, 2014

Participant flow

Participant flow — Overall Study
MilestoneAll Participants
Started22
Received at least 1 dose of study drug22
Drug-drug interaction population18
Completed18
Not completed4
Withdrew: Progressive disease2
Withdrew: Lost to follow-up2

Outcome measures

PrimaryPharmacokinetics: Dose-Normalized Area Under the Concentration Versus Time Curve of Docetaxel From Time Zero to Infinity [AUC(0-∞)] Following a Single Dose in Cycle 1
Time frame:
Cycle 1: 0, 1, 1.5, 2, 3, 5, 7, 24, 48 and 72 hours post docetaxel infusion
Reported as:
Geometric mean · nanograms*hour/milliliter/milligram
Pharmacokinetics: Dose-Normalized Area Under the Concentration Versus Time Curve of Docetaxel From Time Zero to Infinity [AUC(0-∞)] Following a Single Dose in Cycle 1
nanograms*hour/milliliter/milligramDocetaxel (Cycle 1)
Pharmacokinetics: Dose-Normalized Area Under the Concentration Versus Time Curve of Docetaxel From Time Zero to Infinity [AUC(0-∞)] Following a Single Dose in Cycle 113.7 ± 40
PrimaryPharmacokinetics: Dose-Normalized Area Under the Concentration Versus Time Curve of Docetaxel From Time Zero to Infinity [AUC(0-∞)] Following a Single Dose in Cycle 2
Time frame:
Cycle 2: 0, 1, 1.5, 2, 3, 5, 7, 24, 48 and 72 hours post docetaxel infusion
Reported as:
Geometric mean · nanograms*hour/milliliter/milligram
Pharmacokinetics: Dose-Normalized Area Under the Concentration Versus Time Curve of Docetaxel From Time Zero to Infinity [AUC(0-∞)] Following a Single Dose in Cycle 2
nanograms*hour/milliliter/milligramDocetaxel (Cycle 2)
Pharmacokinetics: Dose-Normalized Area Under the Concentration Versus Time Curve of Docetaxel From Time Zero to Infinity [AUC(0-∞)] Following a Single Dose in Cycle 212.8 ± 30
Statistical analysis
  • Docetaxel (Cycle 2) · Mixed Models Analysis · Ratio geometric least squares (ls) means: 0.97 · 90% CI 0.84 to 1.10The ratio of geometric LS means was calculated using a mixed effect model adjusted for cycle, participant and random error. Ratio of geometric LS means is AUC(0-∞) of Cycle 2/Cycle 1.
PrimaryPharmacokinetics: Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Docetaxel in Cycle 1
Time frame:
Cycle 1: 0, 1, 1.5, 2, 3, 5, 7, 24, 48, and 72 hours post docetaxel infusion
Reported as:
Geometric mean · nanograms/milliliter/milligram
Pharmacokinetics: Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Docetaxel in Cycle 1
nanograms/milliliter/milligramDocetaxel (Cycle 1)
Pharmacokinetics: Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Docetaxel in Cycle 17.66 ± 76
PrimaryPharmacokinetics: Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Docetaxel in Cycle 2
Time frame:
Cycle 2: 0, 1, 1.5, 2, 3, 5, 7, 24, 48 and 72 hours post docetaxel infusion
Reported as:
Geometric mean · nanograms/milliliter/milligram
Pharmacokinetics: Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Docetaxel in Cycle 2
nanograms/milliliter/milligramDocetaxel (Cycle 2)
Pharmacokinetics: Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Docetaxel in Cycle 28.78 ± 37
Statistical analysis
  • Docetaxel (Cycle 2) · Mixed Models Analysis · Ratio of geometric least squares means: 1.14 · 90% CI 0.84 to 1.55The ratio of geometric least squares means was calculated using a mixed effect model adjusted for cycle, participant and random error. Ratio of Geo LS mean is Cmax of Cycle 2/Cycle 1.
SecondaryNumber of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies

Participants with treatment-emergent anti-ramucirumab antibodies were participants with a 4-fold increase (2 dilution increase) in immunogenicity titer over baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20).

Time frame:
Cycle 1, Day 1 through Cycle 2, Day 1 and 30 days after last dose of study drug
Reported as:
Number · participants
Number of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies
participantsAll Participants
Immunogenicity During Study (n=17)0
Immunogenicity Post-Treatment (n=5)0
SecondaryPharmacokinetics: Area Under the Concentration Versus Time Curve of Ramucirumab From Time Zero to Infinity [AUC(0-∞)] in the Presence of Docetaxel
Time frame:
Cycle 2: 1 hour prior to ramucirumab infusion, 0, 1, 2, 2.5, 3, 4, 6, 8, 25, 49, 73, 169, 265 and 337 hours post ramucirumab infusion
Reported as:
Geometric mean · micrograms*hour/milliliter (mcg*h/mL)
Pharmacokinetics: Area Under the Concentration Versus Time Curve of Ramucirumab From Time Zero to Infinity [AUC(0-∞)] in the Presence of Docetaxel
micrograms*hour/milliliter (mcg*h/mL)Ramucirumab
Pharmacokinetics: Area Under the Concentration Versus Time Curve of Ramucirumab From Time Zero to Infinity [AUC(0-∞)] in the Presence of Docetaxel42400 ± 32
SecondaryPharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Ramucirumab in the Presence of Docetaxel
Time frame:
Cycle 2: 1 hour prior to ramucirumab infusion, 0, 1, 2, 2.5, 3, 4, 6, 8, 25, 49, 73, 169, 265 and 337 hours post ramucirumab infusion
Reported as:
Geometric mean · micrograms/milliliter (mcg/mL)
Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Ramucirumab in the Presence of Docetaxel
micrograms/milliliter (mcg/mL)Ramucirumab
Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Ramucirumab in the Presence of Docetaxel303.6 ± 28

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
All Participants—11/22 (50%)20/22 (90.9%)
Most frequent serious events
Showing 10 of 22
Most frequent serious events
EventAll Participants
Febrile neutropeniaBlood and lymphatic system disorders4/22
PyrexiaGeneral disorders2/22
PneumoniaInfections and infestations2/22
Muscular weaknessMusculoskeletal and connective tissue disorders2/22
DyspnoeaRespiratory, thoracic and mediastinal disorders2/22
NeutropeniaBlood and lymphatic system disorders1/22
Vision blurredEye disorders1/22
Abdominal painGastrointestinal disorders1/22
ConstipationGastrointestinal disorders1/22
DiarrhoeaGastrointestinal disorders1/22
Most frequent other events
Showing 10 of 52
Most frequent other events
EventAll Participants
NauseaGastrointestinal disorders12/22
FatigueGeneral disorders9/22
White blood cell count decreasedInvestigations9/22
HypertensionVascular disorders7/22
AnaemiaBlood and lymphatic system disorders6/22
HyperglycaemiaMetabolism and nutrition disorders6/22
HyponatraemiaMetabolism and nutrition disorders6/22
CoughRespiratory, thoracic and mediastinal disorders6/22
DyspnoeaRespiratory, thoracic and mediastinal disorders6/22
Decreased appetiteMetabolism and nutrition disorders5/22

Baseline characteristics

All participants who received at least 1 dose of ramucirumab or docetaxel.

Age, Categorical
Age, Categorical(Participants)All Participants
<=18 years0
Between 18 and 65 years14
>=65 years8
Sex: Female, Male
Sex: Female, Male(Participants)All Participants
Female9
Male13
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)All Participants
Hispanic or Latino0
Not Hispanic or Latino22
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)All Participants
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander1
Black or African American4
White17
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)All Participants
United States22
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Study locations

6 sites
  • ImClone Investigational Site
    Ann Arbor, Michigan 48109, United States
  • ImClone Investigational Site
    Detroit, Michigan 48202, United States
  • ImClone Investigational Site
    New Brunswick, New Jersey 08901, United States
  • ImClone Investigational Site
    Huntersville, North Carolina 28078, United States
  • ImClone Investigational Site
    Cleveland, Ohio 44195, United States
  • ImClone Investigational Site
    Seattle, Washington 98109, United States
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 16, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01567163
Lead sponsor
Eli Lilly and Company
Responsible party
Sponsor
First posted
Mar 30, 2012
Start date
Jul 2012
Primary completion
Dec 2012
Completion
Mar 2014
Results posted
Jun 18, 2014
Last update
Oct 16, 2014

Study contacts

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
study director · Eli Lilly and Company

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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