Trial Outcomes & Findings for GDC-0941 and Cisplatin in Treating Patients With Androgen Receptor-Negative Triple Negative Metastatic Breast Cancer (NCT NCT01918306)

NCT ID: NCT01918306

Last Updated: 2017-06-27

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

11 participants

Primary outcome timeframe

4 weeks

Results posted on

2017-06-27

Participant Flow

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

Participant milestones

Participant milestones
Measure	1PHIbA - Arm A - Cisplatin + GDC -0941 Dose Level 1 Cohort 1&2 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.	2PHII1 - Arm 1 - Cisplatin Only 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	2PHII2 - Arm 2 - Cisplatin and GDC-0941 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
Overall Study STARTED	6	2	3
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	6	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	1PHIbA - Arm A - Cisplatin + GDC -0941 Dose Level 1 Cohort 1&2 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.	2PHII1 - Arm 1 - Cisplatin Only 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	2PHII2 - Arm 2 - Cisplatin and GDC-0941 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
Overall Study progresive disease	4	1	1
Overall Study Withdrawal by Subject	0	0	2
Overall Study neutropenia	1	0	0
Overall Study Lack of Efficacy	1	0	0
Overall Study progress disease, crossover	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cisplatin n=2 Participants 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	Cisplatin and GDC-0941 n=9 Participants 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 n=11 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	9 Participants n=7 Participants	10 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Continuous	62 years STANDARD_DEVIATION 15.556 • n=5 Participants	51.3 years STANDARD_DEVIATION 10.1000 • n=7 Participants	53.08 years STANDARD_DEVIATION 11.081 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	9 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	2 participants n=5 Participants	9 participants n=7 Participants	11 participants n=5 Participants

PRIMARY outcome

Timeframe: 4 weeks

Population: 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.

Outcome measures

Outcome measures
Measure	1PHIbA -Cisplatin and GDC-0941 n=6 Participants 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.	2PHII2 Arm 2 - Cisplatin and GDC-0941 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	2PHIICO - Crossover to Arm 2 - Cisplatin and GDC-0941 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
Maximum Tolerated Dose(MTD) of GDC-0941 and Recommended Phase II Dose of GDC-0941 Given in Combination With Cisplatin. - (Phase Ib)	260 mg	—	—

PRIMARY outcome

Timeframe: at 8 weeks

Population: 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.

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.

Outcome measures

Outcome measures
Measure	1PHIbA -Cisplatin and GDC-0941 n=2 Participants 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.	2PHII2 Arm 2 - Cisplatin and GDC-0941 n=3 Participants 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	2PHIICO - Crossover to Arm 2 - Cisplatin and GDC-0941 n=1 Participants 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
Percentage of Patients Achieving Overall Response - (Phase II)	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: During the first 4 weeks

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

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

Outcome measures

Outcome measures
Measure	1PHIbA -Cisplatin and GDC-0941 n=3 Participants 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.	2PHII2 Arm 2 - Cisplatin and GDC-0941 n=3 Participants 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	2PHIICO - Crossover to Arm 2 - Cisplatin and GDC-0941 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
Number of Patients With Dose-limiting Toxicities Per NCI Common Terminology for Adverse Events (CTCAE) - (Phase Ib)	0 participants	1 participants	—

SECONDARY outcome

Timeframe: at 32 weeks

Population: Study closed early and response and progression were not evaluated 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.

Outcome measures

Outcome measures
Measure	1PHIbA -Cisplatin and GDC-0941 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.	2PHII2 Arm 2 - Cisplatin and GDC-0941 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	2PHIICO - Crossover to Arm 2 - Cisplatin and GDC-0941 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
Clinical Benefit Rate - (Phase II)	0	0	0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	1PHIbA -Cisplatin and GDC-0941 n=2 Participants 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.	2PHII2 Arm 2 - Cisplatin and GDC-0941 n=3 Participants 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	2PHIICO - Crossover to Arm 2 - Cisplatin and GDC-0941 n=1 Participants 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
Time to Progression - (Phase II)	24.5 days to progression Interval 9.0 to 40.0	NA days to progression Interval 56.0 to 56.0 1 patient progressed at 56 days, one expired at 464 days, and the other did not progress at the end of study. Median is estimated using Kaplan-meier method.	33 days to progression Interval 33.0 to 33.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 years

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

Outcome measures

Outcome data not reported

Adverse Events

1PHIbA - Arm A - Cisplatin + GDC - 0941 Dose Level 1

Serious events: 0 serious events

Other events: 6 other events

Deaths: 6 deaths

1PHIbB - Arm B - Cisplatin + GDC -0941 Dose Level -1

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

2PHII 1 - Arm 1 - Cisplatin Only

Serious events: 1 serious events

Other events: 2 other events

Deaths: 1 deaths

2PHII2 - Arm 2 - Cisplatin and GDC-0941

Serious events: 1 serious events

Other events: 3 other events

Deaths: 2 deaths

2PHIICO - Crossover to Arm 2 - Cistplatin + GDC -0941

Serious events: 0 serious events

Other events: 1 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	1PHIbA - Arm A - Cisplatin + GDC - 0941 Dose Level 1 n=6 participants at risk 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.	1PHIbB - Arm B - Cisplatin + GDC -0941 Dose Level -1 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.	2PHII 1 - Arm 1 - Cisplatin Only n=2 participants at risk 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	2PHII2 - Arm 2 - Cisplatin and GDC-0941 n=3 participants at risk 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	2PHIICO - Crossover to Arm 2 - Cistplatin + GDC -0941 n=1 participants at risk 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
Cardiac disorders pericardial effusion	0.00% 0/6	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 1	0.00% 0/1
Nervous system disorders paresthesia	0.00% 0/6	— 0/0	50.0% 1/2 • Number of events 1	0.00% 0/3	0.00% 0/1

Other adverse events

Other adverse events
Measure	1PHIbA - Arm A - Cisplatin + GDC - 0941 Dose Level 1 n=6 participants at risk 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.	1PHIbB - Arm B - Cisplatin + GDC -0941 Dose Level -1 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.	2PHII 1 - Arm 1 - Cisplatin Only n=2 participants at risk 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	2PHII2 - Arm 2 - Cisplatin and GDC-0941 n=3 participants at risk 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	2PHIICO - Crossover to Arm 2 - Cistplatin + GDC -0941 n=1 participants at risk 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
Metabolism and nutrition disorders hypomagnesia	83.3% 5/6 • Number of events 10	— 0/0	100.0% 2/2 • Number of events 3	100.0% 3/3 • Number of events 3	0.00% 0/1
Metabolism and nutrition disorders hyperglycemia	16.7% 1/6 • Number of events 1	— 0/0	50.0% 1/2 • Number of events 3	100.0% 3/3 • Number of events 7	100.0% 1/1 • Number of events 1
Metabolism and nutrition disorders hyponatremia	16.7% 1/6 • Number of events 1	— 0/0	50.0% 1/2 • Number of events 1	100.0% 3/3 • Number of events 4	0.00% 0/1
Metabolism and nutrition disorders hypocalcemia	16.7% 1/6 • Number of events 1	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 3	0.00% 0/1
Metabolism and nutrition disorders anorexia	0.00% 0/6	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 1	0.00% 0/1
Metabolism and nutrition disorders dehydration	0.00% 0/6	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 1	0.00% 0/1
Metabolism and nutrition disorders hypokalemia	16.7% 1/6 • Number of events 1	— 0/0	0.00% 0/2	0.00% 0/3	0.00% 0/1
Gastrointestinal disorders nausea	66.7% 4/6 • Number of events 4	— 0/0	50.0% 1/2 • Number of events 1	100.0% 3/3 • Number of events 5	0.00% 0/1
Gastrointestinal disorders diarrhea	66.7% 4/6 • Number of events 4	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 4	0.00% 0/1
Gastrointestinal disorders constipation	33.3% 2/6 • Number of events 2	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 3	0.00% 0/1
Gastrointestinal disorders dyspepsia	16.7% 1/6 • Number of events 1	— 0/0	0.00% 0/2	66.7% 2/3 • Number of events 3	0.00% 0/1
Gastrointestinal disorders vomiting	33.3% 2/6 • Number of events 3	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 1	0.00% 0/1
Metabolism and nutrition disorders gastroesophageal reflux disease	16.7% 1/6 • Number of events 2	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 1	0.00% 0/1
Gastrointestinal disorders mucositis oral	16.7% 1/6 • Number of events 1	— 0/0	0.00% 0/2	0.00% 0/3	0.00% 0/1
Investigations platelet count decreased	50.0% 3/6 • Number of events 8	— 0/0	50.0% 1/2 • Number of events 1	66.7% 2/3 • Number of events 5	0.00% 0/1
Investigations white blood cell decreased	50.0% 3/6 • Number of events 5	— 0/0	0.00% 0/2	100.0% 3/3 • Number of events 13	0.00% 0/1
Investigations neutrophil count decreased	33.3% 2/6 • Number of events 3	— 0/0	0.00% 0/2	66.7% 2/3 • Number of events 7	0.00% 0/1
Investigations alanine aminotransferase increased	16.7% 1/6 • Number of events 2	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 2	0.00% 0/1
Investigations alkaline phosphatase increased	16.7% 1/6 • Number of events 1	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 1	0.00% 0/1
Investigations aspartate aminotransferase increased	16.7% 1/6 • Number of events 1	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 1	0.00% 0/1
Investigations blood bilirubin increased	0.00% 0/6	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 3	0.00% 0/1
Investigations creatinine increased	0.00% 0/6	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 2	0.00% 0/1
Investigations weight loss	0.00% 0/6	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 1	0.00% 0/1
Nervous system disorders dizziness	0.00% 0/6	— 0/0	0.00% 0/2	66.7% 2/3 • Number of events 2	100.0% 1/1 • Number of events 1
Nervous system disorders dysgeusia	33.3% 2/6 • Number of events 2	— 0/0	0.00% 0/2	0.00% 0/3	0.00% 0/1
Nervous system disorders headache	16.7% 1/6 • Number of events 1	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 1	0.00% 0/1
Nervous system disorders peripheral sensory neuropathy	16.7% 1/6 • Number of events 1	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 2	0.00% 0/1
Nervous system disorders acoustic nerve disorder NOS	0.00% 0/6	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 1	0.00% 0/1
Nervous system disorders paresthesia	0.00% 0/6	— 0/0	50.0% 1/2 • Number of events 1	0.00% 0/3	0.00% 0/1
Nervous system disorders syncope	0.00% 0/6	— 0/0	0.00% 0/2	0.00% 0/3	100.0% 1/1 • Number of events 1
Blood and lymphatic system disorders anemia	50.0% 3/6 • Number of events 4	— 0/0	50.0% 1/2 • Number of events 2	100.0% 3/3 • Number of events 6	100.0% 1/1 • Number of events 1
General disorders fatigue	33.3% 2/6 • Number of events 2	— 0/0	0.00% 0/2	100.0% 3/3 • Number of events 11	0.00% 0/1
General disorders fever	16.7% 1/6 • Number of events 1	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 2	0.00% 0/1
General disorders chills	16.7% 1/6 • Number of events 1	— 0/0	0.00% 0/2	0.00% 0/3	0.00% 0/1
General disorders malaise	0.00% 0/6	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 1	0.00% 0/1
General disorders pain	0.00% 0/6	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 1	0.00% 0/1
Respiratory, thoracic and mediastinal disorders cough	33.3% 2/6 • Number of events 2	— 0/0	0.00% 0/2	0.00% 0/3	0.00% 0/1
Respiratory, thoracic and mediastinal disorders dyspnea	16.7% 1/6 • Number of events 1	— 0/0	50.0% 1/2 • Number of events 1	33.3% 1/3 • Number of events 1	0.00% 0/1
Respiratory, thoracic and mediastinal disorders nasal congestion	0.00% 0/6	— 0/0	50.0% 1/2 • Number of events 1	33.3% 1/3 • Number of events 1	0.00% 0/1
Respiratory, thoracic and mediastinal disorders postnasal drip	16.7% 1/6 • Number of events 1	— 0/0	0.00% 0/2	0.00% 0/3	0.00% 0/1
Skin and subcutaneous tissue disorders rash maculopapular	16.7% 1/6 • Number of events 1	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 1	0.00% 0/1
Skin and subcutaneous tissue disorders nail loss	0.00% 0/6	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 1	0.00% 0/1
Skin and subcutaneous tissue disorders rash acneiform	16.7% 1/6 • Number of events 1	— 0/0	0.00% 0/2	0.00% 0/3	0.00% 0/1
Musculoskeletal and connective tissue disorders back pain	16.7% 1/6 • Number of events 1	— 0/0	50.0% 1/2 • Number of events 1	33.3% 1/3 • Number of events 1	0.00% 0/1
Musculoskeletal and connective tissue disorders arthralgia	0.00% 0/6	— 0/0	50.0% 1/2 • Number of events 1	33.3% 1/3 • Number of events 1	0.00% 0/1
Musculoskeletal and connective tissue disorders hot flashes	16.7% 1/6 • Number of events 1	— 0/0	50.0% 1/2 • Number of events 1	33.3% 1/3 • Number of events 1	0.00% 0/1
Vascular disorders thromboembolic event	0.00% 0/6	— 0/0	50.0% 1/2 • Number of events 1	0.00% 0/3	0.00% 0/1
Infections and infestations upper respiratory infection	16.7% 1/6 • Number of events 1	— 0/0	50.0% 1/2 • Number of events 1	33.3% 1/3 • Number of events 1	0.00% 0/1
Psychiatric disorders anxiety	16.7% 1/6 • Number of events 1	— 0/0	50.0% 1/2 • Number of events 1	0.00% 0/3	0.00% 0/1
Psychiatric disorders depression	0.00% 0/6	— 0/0	50.0% 1/2 • Number of events 1	33.3% 1/3 • Number of events 1	0.00% 0/1
Cardiac disorders pericardial effusion	0.00% 0/6	— 0/0	50.0% 1/2 • Number of events 1	33.3% 1/3 • Number of events 1	0.00% 0/1
Ear and labyrinth disorders tinnitus	0.00% 0/6	— 0/0	50.0% 1/2 • Number of events 1	33.3% 1/3 • Number of events 1	0.00% 0/1
Metabolism and nutrition disorders hyperkalemia	16.7% 1/6 • Number of events 1	— 0/0	0.00% 0/2	0.00% 0/3	0.00% 0/1
Musculoskeletal and connective tissue disorders other	0.00% 0/6	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 1	0.00% 0/1
Gastrointestinal disorders abdominal pain	0.00% 0/6	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 1	0.00% 0/1
Gastrointestinal disorders esophageal pain	0.00% 0/6	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 2	0.00% 0/1
Gastrointestinal disorders gastritis	0.00% 0/6	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 1	0.00% 0/1
Gastrointestinal disorders other	0.00% 0/6	— 0/0	0.00% 0/2	33.3% 1/3 • Number of events 1	0.00% 0/1
Skin and subcutaneous tissue disorders other	0.00% 0/6	— 0/0	0.00% 0/2	0.00% 0/3	100.0% 1/1 • Number of events 1

Additional Information

Dr. Vandana Abramson

Vanderbilt-Ingram Cancer Center

Phone: 800-811-8480

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place