Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 37 of 103 for:    "Kennedy disease"

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01918306
Recruitment Status : Terminated (company stopped production of study drug due to excessive toxicities, lack of efficacy)
First Posted : August 7, 2013
Results First Posted : June 27, 2017
Last Update Posted : June 27, 2017
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Genentech, Inc.
Information provided by (Responsible Party):
Vandana Abramson, Vanderbilt-Ingram Cancer Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions 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
Interventions 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
Enrollment 11
Recruitment Details This trial opened to accrual on 9/23/2013 and closed to accrual on 3/9/2016.
Pre-assignment Details  
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
Hide 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 [1] 6 0 [2] 2 [3] 3
Completed 0 0 0 0
Not Completed 6 0 2 3
Reason Not Completed
progresive disease             4             0             1             1
Withdrawal by Subject             0             0             0             2
neutropenia             1             0             0             0
Lack of Efficacy             1             0             0             0
progress disease, crossover             0             0             1             0
[1]
11 total patients. 2 pts received Cisplatin alone. 9 pts started Cisplatin and GDC-0941.
[2]
No patients enrolled
[3]
1 participant Crossed-over to ARM 2
Arm/Group Title Cisplatin Cisplatin and GDC-0941 Total
Hide 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 Number of Baseline Participants 2 9 11
Hide Baseline Analysis Population Description
One participant that is listed in Cisplatin and GDC-0941 arm is a Crossover patient from the Cisplatin only arm.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 9 participants 11 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
1
  50.0%
9
 100.0%
10
  90.9%
>=65 years
1
  50.0%
0
   0.0%
1
   9.1%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 2 participants 9 participants 11 participants
62  (15.556) 51.3  (10.1000) 53.08  (11.081)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 9 participants 11 participants
Female
2
 100.0%
9
 100.0%
11
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 2 participants 9 participants 11 participants
2 9 11
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)
Hide 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

  1. If no patient in the first cohort of 3 experiences a DLT, an additional cohort of 3 patients will be treated at the same dose level.
  2. If 1 patient experiences a DLT in the first cohort, an additional cohort of 3 patients will be treated at the same dose level.
  3. If ≤1 patient has a DLT in 6 treated at this same dose, this will be considered a tolerable dose to move to phase II.
  4. If 2 or more patients in 3 or 6 patients treated at a given dose experience DLT, the dose will be de-escalated to the next lower dose level.
Time Frame 4 weeks
Hide Outcome Measure Data
Hide 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
Hide 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.

Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: mg
260
2.Primary Outcome
Title Percentage of Patients Achieving Overall Response - (Phase II)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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

Overall Number of Participants Analyzed 2 3 1
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
1
  33.3%
0
   0.0%
3.Secondary Outcome
Title Number of Patients With Dose-limiting Toxicities Per NCI Common Terminology for Adverse Events (CTCAE) - (Phase Ib)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 3 3 0
Measure Type: Number
Unit of Measure: participants
0 1
4.Secondary Outcome
Title Clinical Benefit Rate - (Phase II)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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

Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Time to Progression - (Phase II)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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

Overall Number of Participants Analyzed 2 3 1
Median (Full Range)
Unit of Measure: days to progression
24.5
(9 to 40)
NA [1] 
(56 to 56)
33
(33 to 33)
[1]
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.
6.Other Pre-specified Outcome
Title Correlation of the Presence of PIK3CA Mutations in the Tumor With Time to Tumor Progression.
Hide 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 Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
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
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/6 (100.00%)      0/0      1/2 (50.00%)      2/3 (66.67%)      1/1 (100.00%)    
Show Serious Adverse Events Hide 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 (0.00%)      0/0      1/2 (50.00%)      1/3 (33.33%)      0/1 (0.00%)    
Cardiac disorders           
pericardial effusion  0/6 (0.00%)  0/0  0/2 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%) 
Nervous system disorders           
paresthesia  0/6 (0.00%)  0/0  1/2 (50.00%)  1 0/3 (0.00%)  0 0/1 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
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 (100.00%)      0/0      2/2 (100.00%)      3/3 (100.00%)      1/1 (100.00%)    
Blood and lymphatic system disorders           
anemia  3/6 (50.00%)  4 0/0  0 1/2 (50.00%)  2 3/3 (100.00%)  6 1/1 (100.00%)  1
Cardiac disorders           
pericardial effusion  0/6 (0.00%)  0 0/0  0 1/2 (50.00%)  1 1/3 (33.33%)  1 0/1 (0.00%)  0
Ear and labyrinth disorders           
tinnitus  0/6 (0.00%)  0 0/0  0 1/2 (50.00%)  1 1/3 (33.33%)  1 0/1 (0.00%)  0
Gastrointestinal disorders           
nausea  4/6 (66.67%)  4 0/0  0 1/2 (50.00%)  1 3/3 (100.00%)  5 0/1 (0.00%)  0
diarrhea  4/6 (66.67%)  4 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  4 0/1 (0.00%)  0
constipation  2/6 (33.33%)  2 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  3 0/1 (0.00%)  0
dyspepsia  1/6 (16.67%)  1 0/0  0 0/2 (0.00%)  0 2/3 (66.67%)  3 0/1 (0.00%)  0
vomiting  2/6 (33.33%)  3 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
mucositis oral  1/6 (16.67%)  1 0/0  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0
abdominal pain  0/6 (0.00%)  0 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
esophageal pain  0/6 (0.00%)  0 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  2 0/1 (0.00%)  0
gastritis  0/6 (0.00%)  0 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
other  0/6 (0.00%)  0 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
General disorders           
fatigue  2/6 (33.33%)  2 0/0  0 0/2 (0.00%)  0 3/3 (100.00%)  11 0/1 (0.00%)  0
fever  1/6 (16.67%)  1 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  2 0/1 (0.00%)  0
chills  1/6 (16.67%)  1 0/0  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0
malaise  0/6 (0.00%)  0 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
pain  0/6 (0.00%)  0 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
Infections and infestations           
upper respiratory infection  1/6 (16.67%)  1 0/0  0 1/2 (50.00%)  1 1/3 (33.33%)  1 0/1 (0.00%)  0
Investigations           
platelet count decreased  3/6 (50.00%)  8 0/0  0 1/2 (50.00%)  1 2/3 (66.67%)  5 0/1 (0.00%)  0
white blood cell decreased  3/6 (50.00%)  5 0/0  0 0/2 (0.00%)  0 3/3 (100.00%)  13 0/1 (0.00%)  0
neutrophil count decreased  2/6 (33.33%)  3 0/0  0 0/2 (0.00%)  0 2/3 (66.67%)  7 0/1 (0.00%)  0
alanine aminotransferase increased  1/6 (16.67%)  2 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  2 0/1 (0.00%)  0
alkaline phosphatase increased  1/6 (16.67%)  1 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
aspartate aminotransferase increased  1/6 (16.67%)  1 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
blood bilirubin increased  0/6 (0.00%)  0 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  3 0/1 (0.00%)  0
creatinine increased  0/6 (0.00%)  0 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  2 0/1 (0.00%)  0
weight loss  0/6 (0.00%)  0 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
Metabolism and nutrition disorders           
hypomagnesia  5/6 (83.33%)  10 0/0  0 2/2 (100.00%)  3 3/3 (100.00%)  3 0/1 (0.00%)  0
hyperglycemia  1/6 (16.67%)  1 0/0  0 1/2 (50.00%)  3 3/3 (100.00%)  7 1/1 (100.00%)  1
hyponatremia  1/6 (16.67%)  1 0/0  0 1/2 (50.00%)  1 3/3 (100.00%)  4 0/1 (0.00%)  0
hypocalcemia  1/6 (16.67%)  1 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  3 0/1 (0.00%)  0
anorexia  0/6 (0.00%)  0 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
dehydration  0/6 (0.00%)  0 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
hypokalemia  1/6 (16.67%)  1 0/0  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0
gastroesophageal reflux disease  1/6 (16.67%)  2 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
hyperkalemia *  1/6 (16.67%)  1 0/0  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0
Musculoskeletal and connective tissue disorders           
back pain  1/6 (16.67%)  1 0/0  0 1/2 (50.00%)  1 1/3 (33.33%)  1 0/1 (0.00%)  0
arthralgia  0/6 (0.00%)  0 0/0  0 1/2 (50.00%)  1 1/3 (33.33%)  1 0/1 (0.00%)  0
hot flashes  1/6 (16.67%)  1 0/0  0 1/2 (50.00%)  1 1/3 (33.33%)  1 0/1 (0.00%)  0
other  0/6 (0.00%)  0 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
Nervous system disorders           
dizziness  0/6 (0.00%)  0 0/0  0 0/2 (0.00%)  0 2/3 (66.67%)  2 1/1 (100.00%)  1
dysgeusia  2/6 (33.33%)  2 0/0  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0
headache  1/6 (16.67%)  1 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
peripheral sensory neuropathy  1/6 (16.67%)  1 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  2 0/1 (0.00%)  0
acoustic nerve disorder NOS  0/6 (0.00%)  0 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
paresthesia  0/6 (0.00%)  0 0/0  0 1/2 (50.00%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
syncope  0/6 (0.00%)  0 0/0  0 0/2 (0.00%)  0 0/3 (0.00%)  0 1/1 (100.00%)  1
Psychiatric disorders           
anxiety  1/6 (16.67%)  1 0/0  0 1/2 (50.00%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
depression  0/6 (0.00%)  0 0/0  0 1/2 (50.00%)  1 1/3 (33.33%)  1 0/1 (0.00%)  0
Respiratory, thoracic and mediastinal disorders           
cough  2/6 (33.33%)  2 0/0  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0
dyspnea  1/6 (16.67%)  1 0/0  0 1/2 (50.00%)  1 1/3 (33.33%)  1 0/1 (0.00%)  0
nasal congestion  0/6 (0.00%)  0 0/0  0 1/2 (50.00%)  1 1/3 (33.33%)  1 0/1 (0.00%)  0
postnasal drip  1/6 (16.67%)  1 0/0  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0
Skin and subcutaneous tissue disorders           
rash maculopapular  1/6 (16.67%)  1 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
nail loss  0/6 (0.00%)  0 0/0  0 0/2 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
rash acneiform  1/6 (16.67%)  1 0/0  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0
other  0/6 (0.00%)  0 0/0  0 0/2 (0.00%)  0 0/3 (0.00%)  0 1/1 (100.00%)  1
Vascular disorders           
thromboembolic event  0/6 (0.00%)  0 0/0  0 1/2 (50.00%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. Vandana Abramson
Organization: Vanderbilt-Ingram Cancer Center
Phone: 800-811-8480
Responsible Party: Vandana Abramson, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier: NCT01918306     History of Changes
Other Study ID Numbers: VICC BRE 1287
NCI-2013-01319 ( Other Identifier: NCI )
First Submitted: July 25, 2013
First Posted: August 7, 2013
Results First Submitted: September 30, 2016
Results First Posted: June 27, 2017
Last Update Posted: June 27, 2017