A Study of PI3-Kinase Inhibitor GDC-0941 in Combination With Paclitaxel, With and Without Bevacizumab or Trastuzumab, and With Letrozole, in Participants With Locally Recurrent or Metastatic Breast Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 9 January 2017
• Main ID: NCT00960960
• Date of registration: 13/08/2009
• Prospective Registration: No
• Primary sponsor: Genentech, Inc.
• Public title: A Study of PI3-Kinase Inhibitor GDC-0941 in Combination With Paclitaxel, With and Without Bevacizumab or Trastuzumab, and With Letrozole, in Participants With Locally Recurrent or Metastatic Breast Cancer
• Scientific title: A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology of PI3-Kinase Inhibitor GDC-0941 (Pictilisib) in Combination With Paclitaxel, With and Without Bevacizumab or Trastuzumab, and With Letrozole in Patients With Locally Recurrent Or Metastatic Breast Cancer
• Date of first enrolment: August 2009
• Target sample size: 71
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00960960
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

Belgium, Italy, United States

Contacts

• Name: Stina Singel, M.D., Ph.D.
• Affiliation: Genentech, Inc.

Key inclusion & exclusion criteria

Inclusion Criteria:

- Confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease

- Adequate organ and bone marrow function as assessed by laboratory tests

- Evaluable disease or disease measurable per RECIST

- Agreement to use an effective form of contraception for the duration of the study

Exclusion Criteria:

- History of malabsorption syndrome or other condition that would interfere with
enteral absorption

- Any condition requiring full-dose anticoagulants, such as warfarin, heparin, or
thrombolytic agents

- Prior anti-cancer therapy (e.g., chemotherapy, biologic therapy, radiotherapy, or
hormonal therapy) within 4 weeks or 5 half-lives (whichever is shorter) of the first
dose of study treatment

- Uncontrolled current illness

- Active small or large intestine inflammation (such as Crohn's disease or ulcerative
colitis)

- Clinically significant history of liver disease, including cirrhosis, current alcohol
abuse, or current known active infection with human immunodeficiency virus (HIV),
hepatitis B virus, or hepatitis C virus

- Known HIV infection

- New York Heart Association (NYHA) Class II or greater congestive heart failure

- Active ventricular arrhythmia requiring medication

- Pregnancy, lactation, or breastfeeding

- Known significant hypersensitivity to study drugs or excipients

- History of arterial thromboembolic disease within 6 months of first study treatment

- No more than two prior chemotherapy regimens for metastatic disease



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Breast Cancer

Intervention(s)

Drug: Letrozole

Drug: Paclitaxel

Drug: Bevacizumab

Drug: Trastuzumab

Drug: Pictilisib

Primary Outcome(s)

Recommended Phase II Dose (RP2D) of Pictilisib [Time Frame: Baseline up to 54.2 months]

Maximum Tolerated Dose (MTD) of Pictilisib [Time Frame: First treatment cycle (Day 1 up to Day 29)]

Number of Cycles of Each Component of the Treatment Regimen [Time Frame: Baseline up to 54.2 months]

Dose Intensity of Each Component of the Treatment Regimen [Time Frame: Baseline up to 54.2 months]

Percentage of Participants With Dose-Limiting Toxicities (DLTs) [Time Frame: First treatment cycle (Day 1 up to Day 29)]

Secondary Outcome(s)

Cmax of Paclitaxel [Time Frame: Parts 1 and 2 (dose escalation): D2 and D16 of C1; study completion. Part 2 (dose expansion): D1 and D16 of C1; study completion (cycle length=28 days; up to 55.5 months) [detailed timeframe is provided in endpoint description]]

Cmax of Letrozole [Time Frame: Part 3: 1,2,3,4,8h postdose on D15 of C1; Predose (0h) on D1 of C1, C2-6, C=7, D15 of C1 (cycle length=28 days; up to 54.5 months)]

Minimum Observed Plasma Concentration (Cmin) of Pictilisib [Time Frame: Parts 1 and 2 (dose escalation): predose (0 hours [h]) on Day (D) 1,3,16, and 17 of Cycle (C) 1. Part 2 (dose expansion): predose (0h) on D3,16,17 of C1; Part 3: Predose (0h) on D1 of C1, C2-6, C=7, D15 of C1 (cycle length=28 days; up to 54.5 months)]

Duration of Response According to Modified RECIST [Time Frame: Screening up to disease progression or death up to approximately 55.5 months (assessed at Screening and at the end [Days 22-28] of Cycles 2, 5, 8, and 11 and every 3 cycles thereafter [cycle length=28 days; up to approximately 55.5 months])]

Percentage of Participants With Death or Disease Progression According to Modified RECIST [Time Frame: Screening up to disease progression or death up to approximately 55.5 months (assessed at Screening and at the end [Days 22-28] of Cycles 2, 5, 8, and 11 and every 3 cycles thereafter [cycle length=28 days; up to approximately 55.5 months])]

Maximum Observed Plasma Concentration (Cmax) of Pictilisib [Time Frame: Parts 1 and 2: D1,D3,D16,D17 of C1; study completion. Part 2: D3,D16, D17 of C1; study completion. Part 3: D15 of C1; D1 of C1 to C6, C=7 (cycle length=28 days; up to 54.5 months) [detailed timeframe is provided in endpoint description]]

AUClast of Paclitaxel [Time Frame: Parts 1 and 2 (dose escalation): D2 and D16 of C1; study completion. Part 2 (dose expansion): D1 and D16 of C1; study completion (cycle length=28 days; up to 55.5 months) [detailed timeframe is provided in endpoint description]]

Cmin of Letrozole [Time Frame: Part 3: Predose (0h) on D1 of C1, C2-6, C=7, D15 of C1 (cycle length=28 days; up to 54.5 months)]

Cmin of Paclitaxel [Time Frame: Parts 1 and 2 (dose escalation): pre-paclitaxel infusion (0 h) on D2 and D16 of C1. Part 2 (dose expansion): pre-paclitaxel infusion (0 h) on D1 and D16 of C1 (cycle length=28 days)]

Area Under the Curve From Time Zero to Last Measurable Concentrations (AUClast) of Pictilisib [Time Frame: Parts 1 and 2: D1,D3,D16,D17 of C1; study completion. Part 2: D3,D16, D17 of C1; study completion. Part 3: D15 of C1; D1 of C1 to C6, C=7 (cycle length=28 days; up to 54.5 months) [detailed timeframe is provided in endpoint description]]

AUClast of Letrozole [Time Frame: Part 3: 1,2,3,4,8h postdose on D15 of C1; Predose (0h) on D1 of C1, C2-6, C=7, D15 of C1 (cycle length=28 days; up to 54.5 months)]

Percentage of Participants With Objective Response According to Modified Response Evaluation Criteria in Solid Tumors (RECIST) [Time Frame: Screening up to disease progression or death up to approximately 55.5 months (assessed at Screening and at the end [Days 22-28] of Cycles 2, 5, 8, and 11 and every 3 cycles thereafter [cycle length=28 days; up to approximately 55.5 months])]

Progression-free Survival According to Modified RECIST [Time Frame: Screening up to disease progression or death up to approximately 55.5 months (assessed at Screening and at the end [Days 22-28] of Cycles 2, 5, 8, and 11 and every 3 cycles thereafter [cycle length=28 days; up to approximately 55.5 months])]

Secondary ID(s)

GDC4629g

GO01304

2009-010781-38

Source(s) of Monetary Support

Please refer to primary and secondary sponsors