CClinicalTrials.gg
Sign In
TerminatedNCT01918306Updated Jun 27, 2017Results posted

GDC-0941 and Cisplatin in Treating Patients With Androgen Receptor-Negative Triple Negative Metastatic Breast Cancer

A Phase 1/2 interventional study of cisplatin and laboratory biomarker analysis in Estrogen Receptor Negative Breast Cancer, Human Epidermal Growth Factor 2 Negative Carcinoma of Breast and Triple Negative Breast Cancer, sponsored by Vanderbilt-Ingram Cancer Center. Terminated at 16 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-06-27.

Sponsored by Vanderbilt-Ingram Cancer Center · Phase 1/2, Interventional, and Treatment

Why this study was terminated
company stopped production of study drug due to excessive toxicities, lack of efficacy
Phase
Phase 1/2
Study type
Interventional
Enrollment
11
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This phase I/II trial study evaluates the tolerability and best tolerated dose of the PI3K inhibitor GDC-0941 when given with the chemotherapy cisplatin. This study will also examine how well the combination of GDC-0941 and cisplatin work in treating patients with androgen receptor negative triple negative metastatic breast cancer. Patients will be randomized to receive cisplatin alone or cisplatin with GDC-0941 in the phase II portion. Those receiving cisplatin alone can receive GDC-0941 upon progression of their disease. Cisplatin is a chemotherapy which has been shown to be effective in treating triple negative breast cancer. Preclinical studies show that adding a PI3K inhibitor such as GDC-0941 to cisplatin may be a more effective treatment for breast cancer.

Read the detailed description

PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of GDC-0941 when given in combination with cisplatin in patients with androgen receptor-negative (AR-) triple negative (TN) metastatic breast cancer (MBC): assessment of dose limiting toxicities (DLTs) during the first 4 weeks of treatment (cycle 1); determination of the maximally tolerated dose (MTD) and recommended phase II dose of GDC-0941 given in combination with cisplatin. (Phase IB)

II. To evaluate the efficacy, as measured by the overall response rate (ORR), of cisplatin + GDC-0941 versus cisplatin alone in patients with AR- TN MBC. (Phase II)

SECONDARY OBJECTIVES:

I. To determine the clinical benefit rate (CBR) of cisplatin + GDC-0941 in patients with AR- TN MBC.

II. To determine the time to disease progression (TTP) of cisplatin + GDC-0941 versus cisplatin alone in patients with AR- TN MBC.

TERTIARY OBJECTIVES:

I. To characterize pharmacokinetics of GDC-0941 when administered in combination with cisplatin.

II. To explore predictors of response and mechanisms of resistance based on exploratory analysis of tumor tissue obtained through biopsies.

III. To assess the prognostic effects of phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations and phosphatase and tensin homolog (PTEN) loss on TTP and CBR.

OUTLINE: This is a phase I, dose-deescalation study of PI3K inhibitor GDC-0941 followed by a randomized phase II study.

PHASE I: Patients receive cisplatin intravenously (IV) over 1 hour on days 1, 8, and 15 and PI3K inhibitor GDC-0941 orally (PO) once daily (QD) on days 2-6, 9-13, 16-20, and 23-27. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive cisplatin IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may crossover to Arm II upon disease progression.

ARM II: Patients receive cisplatin as in Arm I and PI3K inhibitor GDC-0941 PO QD on days 2-6, 9-13, 16-20, and 23-27. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

02

Conditions studied

  • Estrogen Receptor Negative Breast Cancer
  • Human Epidermal Growth Factor 2 Negative Carcinoma of Breast
  • Triple Negative Breast Cancer
  • Recurrent Breast Cancer
  • Stage IV Breast Cancer
  • Triple-negative Breast Cancer

Keywords

  • Triple Negative Breast Cancer
  • Estrogen receptor negative breast cancer
  • Metastatic breast cancer
  • Stage IV breast cancer
  • HER2 negative breast cancer
03

In context

Breast Neoplasms

12,543 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 11 is below the median of 72 across 9,302 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

Vanderbilt-Ingram Cancer Center is the lead sponsor of 220 studies on the registry; 32 are open to participants now.

Of its 23 completed or terminated interventional studies of FDA-regulated products, 18 (78%) 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

  • Patients must provide informed written consent.
  • Patients must be \<18 years of age.
  • ECOG performance status 0-1.
  • Clinical stage IV invasive mammary carcinoma, ER negative (defined as expression of ER in \< 5% cells), PR negative (defined as expression of PR in \< 5% cells), HER2 negative [acceptable FDA approved methods of HER2 analysis include IHC (0, 1+), fluorescence in situ hybridization (FISH) with HER2/CEN-17 ratio \<2, and/or chromogenic in situ hybridization (CISH)] with HER2/CEN-17 ratio \<2, as previously documented by histological analysis.
  • Androgen receptor negativity, defined as \< 10% of tumor cell nuclei with immunoreactivity for AR in a CLIA certified laboratory. See section 5.1.
  • Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension by RECIST criteria 1.1, with radiologic scans within 21 days of day 1, cycle 1.
  • Up to one prior chemotherapy regimens for metastatic disease.
  • No prior treatment with cisplatin in the metastatic setting.
  • Biopsy of a metastatic lesion in patients with reasonably accessible metastatic lesions (chest wall, skin, subcutaneous tissue, lymph nodes, skin, breast, bones, lung, and liver metastases). If a reasonably accessible site is available for biopsy, the patient must agree to biopsy.
  • Life expectancy ≥ 6 months in the opinion of the investigator

  • Patients must have adequate hematologic, hepatic, and renal function. All tests must be obtained less than 21 days from day 1 of study treatment. This includes:

    • ANC >/=1500/mm3
    • Platelet count >/=100,000/mm3
    • Hemoglobin ≥ 9 g/dL
    • Creatinine \</=1.5X upper limits of normal (ULN)
    • INR ≤ 2
    • Total serum bilirubin ≤ 1.5 x ULN (in patients with known Gilbert Syndrome, a total bilirubin ≤ 3.0 x ULN, with direct bilirubin ≤ 1.5 x ULN)
    • AST and ALT ≤ 3 x ULN (or ≤ 5.0 x ULN if hepatic metastases are present)

    • For patients without known Type II diabetes, the following is required at screening:

      o -Fasting blood glucose \</= 135 mg/dL (7.49 mmol/L) and glycosylated hemoglobin (HbA1c) \<7.0 % or International Federation of Clinical Chemistry (IFCC) \< 53 mmol/mol

    • For patients with Type II diabetes receiving only oral anti-hyperglycemic therapy (patients receiving insulin are not eligible), the following are required at screening:

      • -HbA1c \< 8.5 % or IFCC \< 69.4 mmol/mol
      • -Stable regimen of oral anti-hyperglycemic therapy without insulin usage for at least 3 weeks prior to first study treatment
      • -Fasting blood glucose levels \</= 160 mg/dL (8.88 mmol/L) and no hypoglycemia (BS \<60) during home monitoring for at least 1 week prior to study entry
  • Patients must be able to swallow and retain oral medication.
  • For patients who are not postmenopausal or surgically sterile (absence of ovaries and/or uterus), agreement to remain abstinent or to use two adequate methods of contraception, including at least one method with a failure rate of \< 1% per year (e.g., hormonal implants, combined oral contraceptives, vasectomy/vasectomized partner, tubal ligation), during the treatment period and for at least 30 days after the last dose of GDC-0941 or 6 months after the last dose of cisplatin, whichever is longer; postmenopausal is defined as:
  • Age >/= 60 years
  • Age \</= 60 years and amenorrheic for 12 months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression; and follicle stimulating hormone and estradiol in the postmenopausal range
  • Patients may have received radiation therapy to painful bone metastases or areas of impending bone fracture as long as radiation therapy is completed ≥ 2 weeks prior to day 1 of cycle 1 of treatment. Patients who have received prior radiotherapy must have recovered from toxicity (≤ grade 1) induced by this treatment. Baseline radiologic scans must be obtained after completion of radiation.
  • Patients must complete all screening assessments as outlined in the protocol.

Exclusion criteria

Exclusion Criteria:

  • Any kind of malabsorption syndrome significantly affecting gastrointestinal function.
  • Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, biologic therapy) other than the ones specified in the protocol. Patients must have discontinued the above cancer therapies for 1 week prior to the first dose of study medication, as well as recovered from toxicity (to ≤ than grade 1, except for alopecia) induced by previous treatments. Any investigational drugs should be discontinued 2 weeks prior to the first dose of study medication and radiotherapy must have been completed ≥ 2 weeks prior to initiation of study drug (Cycle 1, Day 1).
  • Prior use of PI3K, or Akt inhibitors in the neoadjuvant, adjuvant, and metastatic setting for the treatment of cancer. These include, but are not limited to: GDC-0941, GDC-0980, GDC-0032, BEZ235, BKM120, LY294002, PIK-75, TGX-221, XL147, XL765, SF1126, PX-866, D-87503, D-106669, GSK615, CAL101. Patients who have received PI3K/Akt inhibitors previously for \<4 weeks will be eligible.
  • Pregnant or lactating women.
  • Insulin-dependent diabetes. Patients with Type II diabetes must meet criteria outlined in Inclusion Criteria.

  • Uncontrolled intercurrent illness including, but not limited to:

    • -Ongoing or active infection requiring parenteral antibiotics
    • -Impairment of lung function (COPD > grade 2, lung conditions requiring oxygen therapy) or current dyspnea at rest
    • -Symptomatic congestive heart failure (class III or IV of the New York Heart Association classification for heart disease)
    • -Known Left Ventricular Ejection Fraction (LVEF) \< 50%.
    • -Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months
    • -Uncontrolled hypertension (systolic blood pressure >160 mm Hg or diastolic blood pressure > 100 mm Hg, found on two consecutive measurements separated by a 1 or 2 week period despite adequate medical support)
    • -Clinically significant cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or requires treatment [National Cancer Institute -Common Terminology Criteria for Adverse Events, Version 4.0, grade 3]
    • -QTcF ≥ 480 msec on screening EKG
    • -Known history of QT/QTc prolongation or Torsades de Pointes (TdP)
    • -ST depression or elevation of ≥ 1.5 mm in 2 or more leads
    • -Diarrhea of any cause ≥ CTCAE grade 2
    • -Active autoimmune disease that is not controlled by nonsteroidal or steroidal (\<10 mg of prednisone per day) anti inflammatory drugs or active inflammatory disease, including small or large intestine inflammation such as active Crohn's disease or ulcerative colitis, which requires immunosuppressive therapy
    • -Psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements including maintenance of a compliance/pill diary
    • -Symptomatic brain metastases (patients with a history of brain metastases must be clinically stable for at least 2 weeks from completion of radiation treatment, on a dose of steroids equivalent to \<10 mg prednisone daily for at least one week, and on a stable dose of therapeutic anticonvulsants)
    • -Known history of chronic liver disease, including cirrhosis, current alcohol abuse, or infection with hepatitis B virus or hepatitis C virus (active or carrier), or renal failure
    • -Known history of chronic pancreatitis
    • -Conditions that affect lymphocyte counts, such as HIV infection or immunosuppressive therapy
  • Use of prohibited drugs
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
11 participants (actual)

Study arms

  • Experimental
    1PHIbA Arm A - cisplatin + GDC - 0941

    Determine the safety and tolerability of GDC-0941 given in combination with cisplatin in patients with AR- TN MBC. Determination of the maximally tolerated dose (MTD) of GDC-0941. Cohort 1, 3 of 3 patients received: Cisplatin 25 mg/m2 IV D1, 8, 15 GDC-0941 260 mg PO, days 2-6, 9-13, 16-20, 23-27, 28 day cycle GDC-0941 dose to start at Max dose of 260mg. If no patient in the first cohort of 3 experiences a DLT, an additional cohort of 3 patients will be treated at the same dose level. 1. If 1 patient experiences a DLT in the first cohort, an additional cohort of 3 patients will be treated at the same dose level. 2. If ≤1 patient has a DLT in 6 treated at this same dose, this will be considered a tolerable dose to move to phase II If patients experience a DLT considered related to GDC-0941, the patient may remain on GDC-0941 and/or Cisplatin after resolution of the DLT. All such cases will be considered a DLT for the purposes of defining the MTD.

    Drug: cisplatin · Other: laboratory biomarker analysis · Other: pharmacological study · Procedure: dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI · Drug: GDC -0941

  • Experimental
    1PHIbB - Arm B - Cisplatin + GDC 0941 dose level -1

    If 2 or more patients in 3 or 6 patients treated at a given dose experience DLT, the dose will be de-escalated to the next lower dose level. Once the lowest dose level is reached, if a DLT occurs, the regimen will be considered too toxic and the corresponding cohort within the study will be discontinued. Determination of the maximally tolerated dose (MTD) of GDC-0941.

    Drug: cisplatin · Other: laboratory biomarker analysis · Other: pharmacological study · Procedure: dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI · Drug: GDC -0941

  • Active comparator
    2PHII1 Arm 1 - Cisplatin

    Evaluate the efficacy, as measured by the overall response rate (ORR), of Cisplatin +GDC-0941 versus Cisplatin alone in patients with AR- TN MBC. Patients will be randomized in a 1:1 fashion to arm 1: cisplatin, or arm 2: cisplatin + GDC-0941. Arm 1 Cisplatin Only Patient received: Cisplatin given intravenously (IV) over 1 hour for three consecutive weeks, then off one week (days 1, 8, and 15 of a 28 day cycle).

    Drug: cisplatin · Other: laboratory biomarker analysis · Other: pharmacological study · Procedure: dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI

  • Experimental
    2PHII2 - Arm 2 - Cisplatin + GDC - 0941

    Evaluate the efficacy, as measured by the overall response rate (ORR), of Cisplatin +GDC-0941 versus Cisplatin alone in patients with AR- TN MBC. Patients are randomized in a 1:1 fashion to arm 1: cisplatin, or arm 2: cisplatin + GDC-0941. Arm 2 Cisplatin + GDC-0941 Patients received: Cisplatin given intravenously (IV) over 1 hour for three consecutive weeks, then off one week (days 1, 8, and 15 of a 28 day cycle). GDC-0941 260 mg PO, administered orally on days 2-6, 9-13, 16-20, 23-27 of a 28 day cycle.

    Drug: cisplatin · Other: laboratory biomarker analysis · Other: pharmacological study · Procedure: dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI · Drug: GDC -0941

  • Experimental
    2PHIICO

    Arm 2: Crossover post-progression Patients who are randomized to Cisplatin alone (Arm 1) can crossover to receive Cisplatin + GDC-0941 upon disease progression. Patient received: Cisplatin given intravenously (IV) over 1 hour for three consecutive weeks, then off one week (days 1, 8, and 15 of a 28 day cycle). GDC-0941 260 mg PO, administered orally on days 2-6, 9-13, 16-20, 23-27 of a 28 day cycle.

    Drug: cisplatin · Other: laboratory biomarker analysis · Other: pharmacological study · Procedure: dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI · Drug: GDC -0941

Interventions

  • Drugcisplatin

    In Arm I patients receive cisplatin IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may crossover to Arm II upon disease progression. In Arm II patients receive cisplatin as in Arm I and PI3K inhibitor GDC-0941 orally (PO) one time a day (QD) on days 2-6, 9-13, 16-20, and 23-27. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. --------------------------------------------------------------------------------

    Also known as: Platinol

  • Otherlaboratory biomarker analysis

    correlative studies

  • Otherpharmacological study

    correlative studies

  • Proceduredynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI

    correlative studies

  • DrugGDC -0941

    Patients receive cisplatin as in Arm I and PI3K inhibitor GDC-0941 PO QD on days 2-6, 9-13, 16-20, and 23-27. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity

06

What researchers measure

Primary outcomes

  1. Maximum Tolerated Dose(MTD) of GDC-0941 and Recommended Phase II Dose of GDC-0941 Given in Combination With Cisplatin. - (Phase Ib)

    GDC-0941 dose will start at 260 mg (maximum dose). De-escalation of the intensity of the dose (if necessary) will proceed among cohorts of 3 patients according to a standard 3+3 algorithm beginning at the highest dose level of GDC-0941 260mg. MTD is defined as the highest dose at which a DLT is experienced \>= 1 out of 6 patients. A cohort of 3 patients was initially enrolled in the GDC-0941 arm at dose 260mg PO days 2-6, 9-13, 16-20, 23-27 of 28 day cycle 1. If no patient in the first cohort of 3 experiences a DLT, an additional cohort of 3 patients will be treated at the same dose level. 2. If 1 patient experiences a DLT in the first cohort, an additional cohort of 3 patients will be treated at the same dose level. 3. If ≤1 patient has a DLT in 6 treated at this same dose, this will be considered a tolerable dose to move to phase II. 4. If 2 or more patients in 3 or 6 patients treated at a given dose experience DLT, the dose will be de-escalated to the next lower dose level.

    Time frame: 4 weeks

  2. Percentage of Patients Achieving Overall Response - (Phase II)

    The primary efficacy endpoint is overall response rate (ORR) of cisplatin + GDC-0941 versus cisplatin alone in patients with AR- TN MBC. ORR is defined as the percentage of subjects achieving complete response (CR) plus partial response (PR) as their best response by RECIST version 1.1 for targeted lesions and assessed by CT, MRI scan. Objective responses, was estimated by the overall tumor burden at baseline (targeted lesions) in which subsequent measurements were performed every 8 weeks using the Solid Tumor Response Criteria (RECIST) v1.1 were compared. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    Time frame: at 8 weeks

Secondary outcomes

  1. Number of Patients With Dose-limiting Toxicities Per NCI Common Terminology for Adverse Events (CTCAE) - (Phase Ib)

    Number of patients with Grade 3 and 4 toxicities per NCI Common Terminology for Adverse Events (CTCAE) version 4.0 requirements.

    Time frame: During the first 4 weeks

  2. Clinical Benefit Rate - (Phase II)

    Clinical Benefit Rate (CBR) is defined as complete response (CR) plus partial response (PR) plus stable disease (SD) for 6 months. Clinical Benefit Rate (CBR) is calculated with the corresponding 95% confidence intervals at the dose recommended for phase II. Response and progression will be evaluated using the international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 performed at baseline and every 8 weeks will be compared.

    Time frame: at 32 weeks

  3. Time to Progression - (Phase II)

    Time to Progression (TTP) is calculated with the corresponding 95% confidence interval at the dose recommended for phase II. TTP is defined as the time from randomization until objective tumor progression, this does not include deaths unrelated to disease progression.

    Time frame: From time of randomization to disease progression, up to 104 weeks

Other outcomes

  1. Correlation of the Presence of PIK3CA Mutations in the Tumor With Time to Tumor Progression.

    Examining tumor tissue for PI3K mutations and correlating this statistically with clinical outcomes including time to tumor progression.

    Time frame: 2 years

07

Results

Posted Jun 27, 2017

Participant flow

This trial opened to accrual on 9/23/2013 and closed to accrual on 3/9/2016.

Participant flow — Overall Study
Milestone1PHIbA - Arm A - Cisplatin + GDC -0941 Dose Level 1 Cohort 1&21PHIbB - Arm B - Cisplatin + GDC -0941 Dose Level -12PHII1 - Arm 1 - Cisplatin Only2PHII2 - Arm 2 - Cisplatin and GDC-0941
Started6023
Completed0000
Not completed6023
Withdrew: Progresive disease4011
Withdrew: Withdrawal by subject0002
Withdrew: Neutropenia1000
Withdrew: Lack of efficacy1000
Withdrew: Progress disease, crossover0010

Outcome measures

PrimaryMaximum Tolerated Dose(MTD) of GDC-0941 and Recommended Phase II Dose of GDC-0941 Given in Combination With Cisplatin. - (Phase Ib)

GDC-0941 dose will start at 260 mg (maximum dose). De-escalation of the intensity of the dose (if necessary) will proceed among cohorts of 3 patients according to a standard 3+3 algorithm beginning at the highest dose level of GDC-0941 260mg. MTD is defined as the highest dose at which a DLT is experienced \>= 1 out of 6 patients. A cohort of 3 patients was initially enrolled in the GDC-0941 arm at dose 260mg PO days 2-6, 9-13, 16-20, 23-27 of 28 day cycle 1. If no patient in the first cohort of 3 experiences a DLT, an additional cohort of 3 patients will be treated at the same dose level. 2. If 1 patient experiences a DLT in the first cohort, an additional cohort of 3 patients will be treated at the same dose level. 3. If ≤1 patient has a DLT in 6 treated at this same dose, this will be considered a tolerable dose to move to phase II. 4. If 2 or more patients in 3 or 6 patients treated at a given dose experience DLT, the dose will be de-escalated to the next lower dose level.

Time frame:
4 weeks
Reported as:
Number · mg
Maximum Tolerated Dose(MTD) of GDC-0941 and Recommended Phase II Dose of GDC-0941 Given in Combination With Cisplatin. - (Phase Ib)
mg1PHIbA -Cisplatin and GDC-0941
Maximum Tolerated Dose(MTD) of GDC-0941 and Recommended Phase II Dose of GDC-0941 Given in Combination With Cisplatin. - (Phase Ib)260
PrimaryPercentage of Patients Achieving Overall Response - (Phase II)

The primary efficacy endpoint is overall response rate (ORR) of cisplatin + GDC-0941 versus cisplatin alone in patients with AR- TN MBC. ORR is defined as the percentage of subjects achieving complete response (CR) plus partial response (PR) as their best response by RECIST version 1.1 for targeted lesions and assessed by CT, MRI scan. Objective responses, was estimated by the overall tumor burden at baseline (targeted lesions) in which subsequent measurements were performed every 8 weeks using the Solid Tumor Response Criteria (RECIST) v1.1 were compared. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Time frame:
at 8 weeks
Reported as:
Count of participants · Participants
Percentage of Patients Achieving Overall Response - (Phase II)
Participants2PHII1 Arm 1 Cisplatin2PHII2 Arm 2 - Cisplatin and GDC-09412PHIICO - Crossover to Arm 2 - Cisplatin and GDC-0941
Percentage of Patients Achieving Overall Response - (Phase II)010
SecondaryNumber of Patients With Dose-limiting Toxicities Per NCI Common Terminology for Adverse Events (CTCAE) - (Phase Ib)

Number of patients with Grade 3 and 4 toxicities per NCI Common Terminology for Adverse Events (CTCAE) version 4.0 requirements.

Time frame:
During the first 4 weeks
Reported as:
Number · participants
Number of Patients With Dose-limiting Toxicities Per NCI Common Terminology for Adverse Events (CTCAE) - (Phase Ib)
participants1PHIbA - Cisplatin and GDC-0941 Cohort 11 PHIbA - Arm 1 - Cisplatin and GDC-0941Cohort 21PHIbB - Arm B - Cistplatin + GDC -0941 Dose Level -1
Number of Patients With Dose-limiting Toxicities Per NCI Common Terminology for Adverse Events (CTCAE) - (Phase Ib)01—
SecondaryClinical Benefit Rate - (Phase II)

Clinical Benefit Rate (CBR) is defined as complete response (CR) plus partial response (PR) plus stable disease (SD) for 6 months. Clinical Benefit Rate (CBR) is calculated with the corresponding 95% confidence intervals at the dose recommended for phase II. Response and progression will be evaluated using the international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 performed at baseline and every 8 weeks will be compared.

Time frame:
at 32 weeks
Clinical Benefit Rate - (Phase II)
Measure2 PHII1 - ARM 1 Cisplatin2PHII2 - ARM 2 - Cisplatin and GDC-09412PHIICO - Crossover to 2 - Cisplatin + GDC-0941
Clinical Benefit Rate - (Phase II)000
SecondaryTime to Progression - (Phase II)

Time to Progression (TTP) is calculated with the corresponding 95% confidence interval at the dose recommended for phase II. TTP is defined as the time from randomization until objective tumor progression, this does not include deaths unrelated to disease progression.

Time frame:
From time of randomization to disease progression, up to 104 weeks
Reported as:
Median · days to progression
Time to Progression - (Phase II)
days to progression2PHII1 - Arm 1 - Cisplatin2PHII2 - Arm 2 - Cisplatin and GDC-09412PHIICO - Crossover to Arm 2 - Cistplatin + GDC - 0941
Time to Progression - (Phase II)24.5 (9 to 40)NA (56 to 56)33 (33 to 33)
Other pre-specifiedCorrelation of the Presence of PIK3CA Mutations in the Tumor With Time to Tumor Progression.

Examining tumor tissue for PI3K mutations and correlating this statistically with clinical outcomes including time to tumor progression.

Time frame:
2 years

Results for this outcome have not been posted.

Adverse events

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

Adverse event summary by group
GroupDeathsSeriousOther
1PHIbA - Arm A - Cisplatin + GDC - 0941 Dose Level 16/6 (100%)0/6 (0%)6/6 (100%)
1PHIbB - Arm B - Cisplatin + GDC -0941 Dose Level -1———
2PHII 1 - Arm 1 - Cisplatin Only1/2 (50%)1/2 (50%)2/2 (100%)
2PHII2 - Arm 2 - Cisplatin and GDC-09412/3 (66.7%)1/3 (33.3%)3/3 (100%)
2PHIICO - Crossover to Arm 2 - Cistplatin + GDC -09411/1 (100%)0/1 (0%)1/1 (100%)
Most frequent serious events
Most frequent serious events
Event1PHIbA - Arm A - Cisplatin + GDC - 0941 Dose Level 11PHIbB - Arm B - Cisplatin + GDC -0941 Dose Level -12PHII 1 - Arm 1 - Cisplatin Only2PHII2 - Arm 2 - Cisplatin and GDC-09412PHIICO - Crossover to Arm 2 - Cistplatin + GDC -0941
paresthesiaNervous system disorders0/6—1/20/30/1
pericardial effusionCardiac disorders0/6—0/21/30/1
Most frequent other events
Showing 10 of 59
Most frequent other events
Event1PHIbA - Arm A - Cisplatin + GDC - 0941 Dose Level 11PHIbB - Arm B - Cisplatin + GDC -0941 Dose Level -12PHII 1 - Arm 1 - Cisplatin Only2PHII2 - Arm 2 - Cisplatin and GDC-09412PHIICO - Crossover to Arm 2 - Cistplatin + GDC -0941
hypomagnesiaMetabolism and nutrition disorders5/6—2/23/30/1
hyperglycemiaMetabolism and nutrition disorders1/6—1/23/31/1
hyponatremiaMetabolism and nutrition disorders1/6—1/23/30/1
nauseaGastrointestinal disorders4/6—1/23/30/1
white blood cell decreasedInvestigations3/6—0/23/30/1
dizzinessNervous system disorders0/6—0/22/31/1
syncopeNervous system disorders0/6—0/20/31/1
anemiaBlood and lymphatic system disorders3/6—1/23/31/1
fatigueGeneral disorders2/6—0/23/30/1
otherSkin and subcutaneous tissue disorders0/6—0/20/31/1

Baseline characteristics

One participant that is listed in Cisplatin and GDC-0941 arm is a Crossover patient from the Cisplatin only arm.

Age, Categorical
Age, Categorical(Participants)CisplatinCisplatin and GDC-0941Total
<=18 years000
Between 18 and 65 years1910
>=65 years101
Age, Continuous
Age, Continuous(years)CisplatinCisplatin and GDC-0941Total
Mean62 ± 15.55651.3 ± 10.100053.08 ± 11.081
Sex: Female, Male
Sex: Female, Male(Participants)CisplatinCisplatin and GDC-0941Total
Female2911
Male000
Region of Enrollment
Region of Enrollment(participants)CisplatinCisplatin and GDC-0941Total
United States2911
08

Study locations

16 sites
  • University of Alabama
    Birmingham, Alabama, United States
  • University of California, San Francisco
    San Francisco, California, United States
  • Georgetown University
    Washington, D.C., District of Columbia, United States
  • Emory University
    Atlanta, Georgia, United States
  • University of Chicago
    Chicago, Illinois, United States
  • Indiana University
    Indianapolis, Indiana, United States
  • John Hopkins University
    Baltimore, Maryland, United States
  • Dana Farber Cancer Institute
    Boston, Massachusetts, United States
  • University of Michigan
    Ann Arbor, Michigan, United States
  • Mayo Clinic
    Rochester, Minnesota, United States
  • Memorial Sloan-Kettering Cancer Center
    New York, New York, United States
  • University of North Carolina
    Charlotte, North Carolina, United States
  • University of Pittsburgh
    Pittsburgh, Pennsylvania, United States
  • Vanderbilt-Ingram Cancer Center
    Nashville, Tennessee 37232, United States
  • Baylor Breast Center
    Houston, Texas, United States
  • University of Washington
    Seattle, Washington, United States
09

References and documents

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 27, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01918306
Lead sponsor
Vanderbilt-Ingram Cancer Center
Collaborators
National Cancer Institute (NCI), Genentech, Inc.
Responsible party
Vandana Abramson (Assistant Professor of Medicine; Medical Oncologist, Vanderbilt-Ingram Cancer Center) — Principal investigator
First posted
Aug 7, 2013
Start date
Sep 2013
Primary completion
Dec 2014
Completion
Apr 2015
Results posted
Jun 27, 2017
Last update
Jun 27, 2017

Study contacts

Vandana G. Abramson, MD
principal investigator · Vanderbilt-Ingram Cancer Center

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is terminated, as verified in May 2017. 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 in this condition

Breast Neoplasms→

Other studies from this sponsor

Vanderbilt-Ingram Cancer Center

Start the discussion