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

• Sponsor: Vanderbilt-Ingram Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01918306
• Collaborator: National Cancer Institute (NCI) (NIH), Genentech, Inc. (Industry)
• Enrollment: 11
• Locations: 16
• Arms: 5
• Duration (Months): 19
• Patients Per Site: 0.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
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	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	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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)

2. 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:

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

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

TERTIARY OBJECTIVES:

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

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

3. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Masking Description: Open label
• Primary Purpose: Treatment
• Official Title: A Phase Ib/II Trial of GDC-0941 (a PI3K Inhibitor) in Combination With Cisplatin in Patients With Androgen Receptor Negative Triple Negative Metastatic Breast Cancer
• Study Start Date: Sep 1, 2013
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
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. If 1 patient experiences a DLT in the first cohort, an additional cohort of 3 patients will be treated at the same dose level. 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; 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. --------------------------------------------------------------------------------; Other Names: Platinol ; Other: laboratory biomarker analysis; correlative studies; Other: pharmacological study; correlative studies; Procedure: dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI; correlative studies; Drug: GDC -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
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; 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. --------------------------------------------------------------------------------; Other Names: Platinol ; Other: laboratory biomarker analysis; correlative studies; Other: pharmacological study; correlative studies; Procedure: dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI; correlative studies; Drug: GDC -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
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; 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. --------------------------------------------------------------------------------; Other Names: Platinol ; Other: laboratory biomarker analysis; correlative studies; Other: pharmacological study; correlative studies; Procedure: dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI; correlative studies
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; 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. --------------------------------------------------------------------------------; Other Names: Platinol ; Other: laboratory biomarker analysis; correlative studies; Other: pharmacological study; correlative studies; Procedure: dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI; correlative studies; Drug: GDC -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
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; 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. --------------------------------------------------------------------------------; Other Names: Platinol ; Other: laboratory biomarker analysis; correlative studies; Other: pharmacological study; correlative studies; Procedure: dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI; correlative studies; Drug: GDC -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

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose(MTD) of GDC-0941 and Recommended Phase II Dose of GDC-0941 Given in Combination With Cisplatin. - (Phase Ib) [4 weeks]

   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 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. If 1 patient experiences a DLT in the first cohort, an additional cohort of 3 patients will be treated at the same dose level. 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 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.

2. Percentage of Patients Achieving Overall Response - (Phase II) [at 8 weeks]

   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.

Secondary Outcome Measures

1. Number of Patients With Dose-limiting Toxicities Per NCI Common Terminology for Adverse Events (CTCAE) - (Phase Ib) [During the first 4 weeks]

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

2. Clinical Benefit Rate - (Phase II) [at 32 weeks]

   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.

3. Time to Progression - (Phase II) [From time of randomization to disease progression, up to 104 weeks]

   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.

Other Outcome Measures

1. Correlation of the Presence of PIK3CA Mutations in the Tumor With Time to Tumor Progression. [2 years]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: 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:

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States
2	University of California, San Francisco	San Francisco	California	United States
3	Georgetown University	Washington, D.C.	District of Columbia	United States
4	Emory University	Atlanta	Georgia	United States
5	University of Chicago	Chicago	Illinois	United States
6	Indiana University	Indianapolis	Indiana	United States
7	John Hopkins University	Baltimore	Maryland	United States
8	Dana Farber Cancer Institute	Boston	Massachusetts	United States
9	University of Michigan	Ann Arbor	Michigan	United States
10	Mayo Clinic	Rochester	Minnesota	United States
11	Memorial Sloan-Kettering Cancer Center	New York	New York	United States
12	University of North Carolina	Charlotte	North Carolina	United States
13	University of Pittsburgh	Pittsburgh	Pennsylvania	United States
14	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232
15	Baylor Breast Center	Houston	Texas	United States
16	University of Washington	Seattle	Washington	United States

Sponsors and Collaborators

• Vanderbilt-Ingram Cancer Center
• National Cancer Institute (NCI)
• Genentech, Inc.

Investigators

• Principal Investigator: Vandana G. Abramson, MD, Vanderbilt-Ingram Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Vanderbilt-Ingram Cancer Center, Find a Clinical Trial

Publications

None provided.

• Responsible Party: Vandana Abramson, Assistant Professor of Medicine; Medical Oncologist, Vanderbilt-Ingram Cancer Center
• ClinicalTrials.gov Identifier: NCT01918306
• Other Study ID Numbers: VICC BRE 1287; NCI-2013-01319
• First Posted: Aug 7, 2013
• Last Update Posted: Jun 27, 2017
• Last Verified: May 1, 2017

• Keywords provided by Vandana Abramson, Assistant Professor of Medicine; Medical Oncologist, Vanderbilt-Ingram Cancer Center: Triple Negative Breast Cancer; Estrogen receptor negative breast cancer; Metastatic breast cancer; Stage IV breast cancer; HER2 negative breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms; Cisplatin

Study Results

Participant Flow

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

Arm/Group Title	1PHIbA - Arm A - Cisplatin + GDC -0941 Dose Level 1 Cohort 1&2	1PHIbB - Arm B - Cisplatin + GDC -0941 Dose Level -1	2PHII1 - Arm 1 - Cisplatin Only	2PHII2 - Arm 2 - Cisplatin and GDC-0941
Arm/Group Description	Patients receive cisplatin and PI3K inhibitor GDC-0941. Courses repeat in the absence of disease progression or unacceptable toxicity. cisplatin: 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. 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.	If 2 or more patients in 3 or 6 patients (cohort 1 and 2) treated at a given dose 260 mg experience DLT, the dose will be de-escalated to the next lower dose level.	Patients receive cisplatin in Arm I. Patients may crossover to Arm II upon disease progression. cisplatin: 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. -------------------------------------------------------------------------------- laboratory biomarker analysis: correlative studies pharmacological study: correlative studies dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI: correlative studies	Patients receive Cisplatin and PI3K inhibitor GDC-0941. Courses repeat in the absence of disease progression or unacceptable toxicity. cisplatin: patients received 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 receive 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. laboratory biomarker analysis: correlative studies pharmacological study: correlative studies dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI: correlative studies
Period Title: Overall Study
STARTED	6	0	2	3
COMPLETED	0	0	0	0
NOT COMPLETED	6	0	2	3

Baseline Characteristics

Arm/Group Title	Cisplatin	Cisplatin and GDC-0941	Total
Arm/Group Description	Patients receive cisplatin in Arm I. Patients may crossover to Arm II upon disease progression. cisplatin: 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. -------------------------------------------------------------------------------- laboratory biomarker analysis: correlative studies pharmacological study: correlative studies dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI: correlative studies	Patients receive cisplatin as in Arm I and PI3K inhibitor GDC-0941. Courses repeat in the absence of disease progression or unacceptable toxicity. cisplatin: 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. -------------------------------------------------------------------------------- GDC -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	Total of all reporting groups
Overall Participants	2	9	11
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	1 50%	9 100%	10 90.9%
>=65 years	1 50%	0 0%	1 9.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62 (15.556)	51.3 (10.1000)	53.08 (11.081)
Sex: Female, Male (Count of Participants)
Female	2 100%	9 100%	11 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	2 100%	9 100%	11 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose(MTD) of GDC-0941 and Recommended Phase II Dose of GDC-0941 Given in Combination With Cisplatin. - (Phase Ib)
Description	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 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. If 1 patient experiences a DLT in the first cohort, an additional cohort of 3 patients will be treated at the same dose level. 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 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

Outcome Measure Data

Analysis Population Description

A cohort of 3 was enrolled at dose 260mg. No DLT was found. Then a second cohort of 260mg was enrolled. One of them experienced DLT.

Arm/Group Title	1PHIbA -Cisplatin and GDC-0941
Arm/Group Description	Patients receive cisplatin and PI3K inhibitor GDC-0941. Courses repeat in the absence of disease progression or unacceptable toxicity. cisplatin: 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. 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.
Measure Participants	6
Number [mg]	260

2. Primary Outcome

Title	Percentage of Patients Achieving Overall Response - (Phase II)
Description	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

Outcome Measure Data

Analysis Population Description

Phase 1-Initial and Max tolerated dose of GCD-0941 was the same, no dose de-escalation occurred. Phase 2, 1 of the 2 patients from the Cisplatin only arm did crossover to the Crossover Cisplatin and GDC-0941 arm. 3 patients randomized to Cisplatin + GDC -0941 arm, and 1 crossover patient, for a total of 4 patients who received Cisplatin+GDC-0941.

Arm/Group Title	2PHII1 Arm 1 Cisplatin	2PHII2 Arm 2 - Cisplatin and GDC-0941	2PHIICO - Crossover to Arm 2 - Cisplatin and GDC-0941
Arm/Group Description	Patients receive cisplatin in Arm I. Patients may crossover to Arm II upon disease progression. cisplatin:patients received 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. laboratory biomarker analysis: correlative studies pharmacological study: correlative studies dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI: correlative studies	Patients receive Cisplatin and PI3K inhibitor GDC-0941. Courses repeat in the absence of disease progression or unacceptable toxicity. cisplatin: patients received 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 receive 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. laboratory biomarker analysis: correlative studies pharmacological study: correlative studies dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI: correlative studies	Crossover patient received Cisplatin and PI3K inhibitor GDC-0941 after found to have disease progression in Cisplatin only arm. Courses repeat in the absence of disease progression or unacceptable toxicity. cisplatin: patients received 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 receive 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. laboratory biomarker analysis: correlative studies pharmacological study: correlative studies dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI: correlative studies
Measure Participants	2	3	1
Count of Participants [Participants]	0 0%	1 11.1%	0 0%

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Less than 2 patients in cohort 1 and 2 experienced DLT, therefore no patients enrolled in arm 1PHIbB.

Arm/Group Title	1PHIbA - Cisplatin and GDC-0941 Cohort 1	1 PHIbA - Arm 1 - Cisplatin and GDC-0941Cohort 2	1PHIbB - Arm B - Cistplatin + GDC -0941 Dose Level -1
Arm/Group Description	Starting dose of GDC - 0941 260mg. 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. (Highest dose = 260mg) In cohort 1 patients received 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 also received 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.	Starting dose of GDC - 0941 260mg, no DLT's experienced in cohort 1. Therefore no de-escalation of the intensity of the dose was necessary. An additional cohort of 3 patients will be treated at the same dose level beginning at the highest dose level. (Highest dose = 260mg) In cohort 2, patients received 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 also received 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. ≤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 2 or more patients in 3 or 6 patients (cohort 1 and 2) treated at a given dose 260 mg experience DLT, the dose will be de-escalated to the next lower dose level.
Measure Participants	3	3	0
Number [participants]	0 0%	1 11.1%

4. Secondary Outcome

Title	Clinical Benefit Rate - (Phase II)
Description	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

Outcome Measure Data

Analysis Population Description

Study closed early and response and progression were not evaluated at 32 weeks.

Arm/Group Title	2 PHII1 - ARM 1 Cisplatin	2PHII2 - ARM 2 - Cisplatin and GDC-0941	2PHIICO - Crossover to 2 - Cisplatin + GDC-0941
Arm/Group Description	Patients receive Cisplatin in Arm I. Patients may crossover to Arm II upon disease progression. Cisplatin: patients received 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. laboratory biomarker analysis: correlative studies pharmacological study: correlative studies dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI: correlative studies	Patients receive Cisplatin and PI3K inhibitor GDC-0941. Courses repeat in the absence of disease progression or unacceptable toxicity. cisplatin: patients received 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 receive 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. laboratory biomarker analysis: correlative studies pharmacological study: correlative studies dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI: correlative studies	Crossover patient received Cisplatin and PI3K inhibitor GDC-0941 after found to have disease progression in Cisplatin only arm. Courses repeat in the absence of disease progression or unacceptable toxicity. cisplatin: patients received 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 receive 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. laboratory biomarker analysis: correlative studies pharmacological study: correlative studies dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI: correlative studies
Measure Participants	0	0	0
	0	0	0

5. Secondary Outcome

Title	Time to Progression - (Phase II)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2PHII1 - Arm 1 - Cisplatin	2PHII2 - Arm 2 - Cisplatin and GDC-0941	2PHIICO - Crossover to Arm 2 - Cistplatin + GDC - 0941
Arm/Group Description	Patients receive Cisplatin in Arm I. Patients may crossover to Arm II upon disease progression. Cisplatin: patients received 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. laboratory biomarker analysis: correlative studies pharmacological study: correlative studies dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI: correlative studies	Patients receive Cisplatin and PI3K inhibitor GDC-0941. Courses repeat in the absence of disease progression or unacceptable toxicity. cisplatin: patients received 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 receive 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. laboratory biomarker analysis: correlative studies pharmacological study: correlative studies dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI: correlative studies	Crossover patient received Cisplatin and PI3K inhibitor GDC-0941 after found to have disease progression in Cisplatin only arm. Courses repeat in the absence of disease progression or unacceptable toxicity. cisplatin: patients received 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 receive 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. laboratory biomarker analysis: correlative studies pharmacological study: correlative studies dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI: correlative studies
Measure Participants	2	3	1
Median (Full Range) [days to progression]	24.5	NA	33

6. Other Pre-specified Outcome

Title	Correlation of the Presence of PIK3CA Mutations in the Tumor With Time to Tumor Progression.
Description	Examining tumor tissue for PI3K mutations and correlating this statistically with clinical outcomes including time to tumor progression.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	1PHIbA - Arm A - Cisplatin + GDC - 0941 Dose Level 1		1PHIbB - Arm B - Cisplatin + GDC -0941 Dose Level -1		2PHII 1 - Arm 1 - Cisplatin Only		2PHII2 - Arm 2 - Cisplatin and GDC-0941		2PHIICO - Crossover to Arm 2 - Cistplatin + GDC -0941
Arm/Group Description	Patients cohort 1 receive cisplatin and PI3K inhibitor GDC-0941. Courses repeat in the absence of disease progression or unacceptable toxicity. cisplatin: 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. 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. If no patients in Cohort 1 experienced DLT's after 4 weeks, all patients in Cohort 2 will receive cisplatin and PI3K inhibitor GDC-0941, GDC-0941dose not to exceed 260mg. If 1 patient experiences a DLT in the first cohort, an additional cohort of 3 patients will be treated at the same dose level in cohort 2. If ≤1 patient has a DLT in 6 (cohort 1 and 2) treated at this same dose, this will be considered a tolerable dose to move to phase II.		If 2 or more patients in 3 or 6 patients (cohort 1 and 2) treated at a given dose 260 mg experience DLT, the dose will be de-escalated to the next lower dose level.		Patients receive cisplatin in Arm I. Patients may crossover to Arm II upon disease progression. cisplatin:patients received 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. -------------------------------------------------------------------------------- laboratory biomarker analysis: correlative studies pharmacological study: correlative studies dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI: correlative studies		Patients receive Cisplatin and PI3K inhibitor GDC-0941. Courses repeat in the absence of disease progression or unacceptable toxicity. cisplatin: patients received 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 receive 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. -------------------------------------------------------------------------------- laboratory biomarker analysis: correlative studies pharmacological study: correlative studies dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI: correlative studies GDC -0941: Patients receive cisplatin as in Arm I and PI3K		Crossover patient received Cisplatin and PI3K inhibitor GDC-0941 after found to have disease progression in Cisplatin only arm. Courses repeat in the absence of disease progression or unacceptable toxicity. cisplatin: patients received 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. patient received 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. laboratory biomarker analysis: correlative studies pharmacological study: correlative studies dynamic contrast-enhanced MRI, diffusion-weighted MRI & chemical exchange saturation transfer MRI: correlative studies
All Cause Mortality
	1PHIbA - Arm A - Cisplatin + GDC - 0941 Dose Level 1		1PHIbB - Arm B - Cisplatin + GDC -0941 Dose Level -1		2PHII 1 - Arm 1 - Cisplatin Only		2PHII2 - Arm 2 - Cisplatin and GDC-0941		2PHIICO - Crossover to Arm 2 - Cistplatin + GDC -0941
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		0/0 (NaN)		1/2 (50%)		2/3 (66.7%)		1/1 (100%)
Serious Adverse Events
	1PHIbA - Arm A - Cisplatin + GDC - 0941 Dose Level 1		1PHIbB - Arm B - Cisplatin + GDC -0941 Dose Level -1		2PHII 1 - Arm 1 - Cisplatin Only		2PHII2 - Arm 2 - Cisplatin and GDC-0941		2PHIICO - Crossover to Arm 2 - Cistplatin + GDC -0941
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/0 (NaN)		1/2 (50%)		1/3 (33.3%)		0/1 (0%)
Cardiac disorders
pericardial effusion	0/6 (0%)		0/0 (NaN)		0/2 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	1
Nervous system disorders
paresthesia	0/6 (0%)		0/0 (NaN)		1/2 (50%)	1	0/3 (0%)	0	0/1 (0%)	0
Other (Not Including Serious) Adverse Events
	1PHIbA - Arm A - Cisplatin + GDC - 0941 Dose Level 1		1PHIbB - Arm B - Cisplatin + GDC -0941 Dose Level -1		2PHII 1 - Arm 1 - Cisplatin Only		2PHII2 - Arm 2 - Cisplatin and GDC-0941		2PHIICO - Crossover to Arm 2 - Cistplatin + GDC -0941
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		0/0 (NaN)		2/2 (100%)		3/3 (100%)		1/1 (100%)
Blood and lymphatic system disorders
anemia	3/6 (50%)	4	0/0 (NaN)	0	1/2 (50%)	2	3/3 (100%)	6	1/1 (100%)	1
Cardiac disorders
pericardial effusion	0/6 (0%)	0	0/0 (NaN)	0	1/2 (50%)	1	1/3 (33.3%)	1	0/1 (0%)	0
Ear and labyrinth disorders
tinnitus	0/6 (0%)	0	0/0 (NaN)	0	1/2 (50%)	1	1/3 (33.3%)	1	0/1 (0%)	0
Gastrointestinal disorders
nausea	4/6 (66.7%)	4	0/0 (NaN)	0	1/2 (50%)	1	3/3 (100%)	5	0/1 (0%)	0
diarrhea	4/6 (66.7%)	4	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	4	0/1 (0%)	0
constipation	2/6 (33.3%)	2	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	3	0/1 (0%)	0
dyspepsia	1/6 (16.7%)	1	0/0 (NaN)	0	0/2 (0%)	0	2/3 (66.7%)	3	0/1 (0%)	0
vomiting	2/6 (33.3%)	3	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
mucositis oral	1/6 (16.7%)	1	0/0 (NaN)	0	0/2 (0%)	0	0/3 (0%)	0	0/1 (0%)	0
abdominal pain	0/6 (0%)	0	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
esophageal pain	0/6 (0%)	0	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	2	0/1 (0%)	0
gastritis	0/6 (0%)	0	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
other	0/6 (0%)	0	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
General disorders
fatigue	2/6 (33.3%)	2	0/0 (NaN)	0	0/2 (0%)	0	3/3 (100%)	11	0/1 (0%)	0
fever	1/6 (16.7%)	1	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	2	0/1 (0%)	0
chills	1/6 (16.7%)	1	0/0 (NaN)	0	0/2 (0%)	0	0/3 (0%)	0	0/1 (0%)	0
malaise	0/6 (0%)	0	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
pain	0/6 (0%)	0	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
Infections and infestations
upper respiratory infection	1/6 (16.7%)	1	0/0 (NaN)	0	1/2 (50%)	1	1/3 (33.3%)	1	0/1 (0%)	0
Investigations
platelet count decreased	3/6 (50%)	8	0/0 (NaN)	0	1/2 (50%)	1	2/3 (66.7%)	5	0/1 (0%)	0
white blood cell decreased	3/6 (50%)	5	0/0 (NaN)	0	0/2 (0%)	0	3/3 (100%)	13	0/1 (0%)	0
neutrophil count decreased	2/6 (33.3%)	3	0/0 (NaN)	0	0/2 (0%)	0	2/3 (66.7%)	7	0/1 (0%)	0
alanine aminotransferase increased	1/6 (16.7%)	2	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	2	0/1 (0%)	0
alkaline phosphatase increased	1/6 (16.7%)	1	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
aspartate aminotransferase increased	1/6 (16.7%)	1	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
blood bilirubin increased	0/6 (0%)	0	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	3	0/1 (0%)	0
creatinine increased	0/6 (0%)	0	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	2	0/1 (0%)	0
weight loss	0/6 (0%)	0	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
Metabolism and nutrition disorders
hypomagnesia	5/6 (83.3%)	10	0/0 (NaN)	0	2/2 (100%)	3	3/3 (100%)	3	0/1 (0%)	0
hyperglycemia	1/6 (16.7%)	1	0/0 (NaN)	0	1/2 (50%)	3	3/3 (100%)	7	1/1 (100%)	1
hyponatremia	1/6 (16.7%)	1	0/0 (NaN)	0	1/2 (50%)	1	3/3 (100%)	4	0/1 (0%)	0
hypocalcemia	1/6 (16.7%)	1	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	3	0/1 (0%)	0
anorexia	0/6 (0%)	0	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
dehydration	0/6 (0%)	0	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
hypokalemia	1/6 (16.7%)	1	0/0 (NaN)	0	0/2 (0%)	0	0/3 (0%)	0	0/1 (0%)	0
gastroesophageal reflux disease	1/6 (16.7%)	2	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
hyperkalemia	1/6 (16.7%)	1	0/0 (NaN)	0	0/2 (0%)	0	0/3 (0%)	0	0/1 (0%)	0
Musculoskeletal and connective tissue disorders
back pain	1/6 (16.7%)	1	0/0 (NaN)	0	1/2 (50%)	1	1/3 (33.3%)	1	0/1 (0%)	0
arthralgia	0/6 (0%)	0	0/0 (NaN)	0	1/2 (50%)	1	1/3 (33.3%)	1	0/1 (0%)	0
hot flashes	1/6 (16.7%)	1	0/0 (NaN)	0	1/2 (50%)	1	1/3 (33.3%)	1	0/1 (0%)	0
other	0/6 (0%)	0	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
Nervous system disorders
dizziness	0/6 (0%)	0	0/0 (NaN)	0	0/2 (0%)	0	2/3 (66.7%)	2	1/1 (100%)	1
dysgeusia	2/6 (33.3%)	2	0/0 (NaN)	0	0/2 (0%)	0	0/3 (0%)	0	0/1 (0%)	0
headache	1/6 (16.7%)	1	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
peripheral sensory neuropathy	1/6 (16.7%)	1	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	2	0/1 (0%)	0
acoustic nerve disorder NOS	0/6 (0%)	0	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
paresthesia	0/6 (0%)	0	0/0 (NaN)	0	1/2 (50%)	1	0/3 (0%)	0	0/1 (0%)	0
syncope	0/6 (0%)	0	0/0 (NaN)	0	0/2 (0%)	0	0/3 (0%)	0	1/1 (100%)	1
Psychiatric disorders
anxiety	1/6 (16.7%)	1	0/0 (NaN)	0	1/2 (50%)	1	0/3 (0%)	0	0/1 (0%)	0
depression	0/6 (0%)	0	0/0 (NaN)	0	1/2 (50%)	1	1/3 (33.3%)	1	0/1 (0%)	0
Respiratory, thoracic and mediastinal disorders
cough	2/6 (33.3%)	2	0/0 (NaN)	0	0/2 (0%)	0	0/3 (0%)	0	0/1 (0%)	0
dyspnea	1/6 (16.7%)	1	0/0 (NaN)	0	1/2 (50%)	1	1/3 (33.3%)	1	0/1 (0%)	0
nasal congestion	0/6 (0%)	0	0/0 (NaN)	0	1/2 (50%)	1	1/3 (33.3%)	1	0/1 (0%)	0
postnasal drip	1/6 (16.7%)	1	0/0 (NaN)	0	0/2 (0%)	0	0/3 (0%)	0	0/1 (0%)	0
Skin and subcutaneous tissue disorders
rash maculopapular	1/6 (16.7%)	1	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
nail loss	0/6 (0%)	0	0/0 (NaN)	0	0/2 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0
rash acneiform	1/6 (16.7%)	1	0/0 (NaN)	0	0/2 (0%)	0	0/3 (0%)	0	0/1 (0%)	0
other	0/6 (0%)	0	0/0 (NaN)	0	0/2 (0%)	0	0/3 (0%)	0	1/1 (100%)	1
Vascular disorders
thromboembolic event	0/6 (0%)	0	0/0 (NaN)	0	1/2 (50%)	1	0/3 (0%)	0	0/1 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.