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

Breast Cancer Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00960960
• Other study ID #: GDC4629g
• Secondary ID: GO013042009-0107
• Status: Completed
• Phase: Phase 1
• First received: August 13, 2009
• Last updated: December 14, 2016
• Start date: August 2009
• Est. completion date: December 2015

Study information

• Verified date: December 2016
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is an open-label, multicenter, Phase Ib dose-escalation study to assess the safety, tolerability, and pharmacokinetics of oral (PO) pictilisib administered with letrozole or intravenous (IV) paclitaxel with and without IV bevacizumab or IV trastuzumab in participants with locally recurrent or metastatic breast cancer. The study consists of three parts. Part 1 (pictilisib will be administered in 21+7 schedule along with paclitaxel and/or bevacizumab), Part 2 (pictilisib will be administered in 5+2 schedule along with paclitaxel and/or bevacizumab or trastuzumab) and Part 3 (pictilisib will be administered in combination with letrozole). Part 1 and Part 2 consists of two stages; a dose escalation stage and a cohort-expansion stage.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Bevacizumab
Bevacizumab will be administered IV at a dose of 10 mg/kg on Days 1 and 15 of each 28-day cycle.
• Pictilisib
Pictilisib will be administered PO QD on escalating doses.
• Letrozole
Letrozole will be administered PO at a dose of 2.5 mg QD for for each 28-day cycle.
• Paclitaxel
Paclitaxel will be administered IV at a dose of 90 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle.
• Trastuzumab
Trastuzumab will be administered IV at a dose of 2-4 mg/kg on on Days 1, 8, 15, and 22 of each 28-day cycle.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Dose-Limiting Toxicities (DLTs)		First treatment cycle (Day 1 up to Day 29)	No
Primary	Maximum Tolerated Dose (MTD) of Pictilisib		First treatment cycle (Day 1 up to Day 29)	No
Primary	Recommended Phase II Dose (RP2D) of Pictilisib		Baseline up to 54.2 months	No
Primary	Number of Cycles of Each Component of the Treatment Regimen		Baseline up to 54.2 months	No
Primary	Dose Intensity of Each Component of the Treatment Regimen		Baseline up to 54.2 months	No
Secondary	Minimum Observed Plasma Concentration (Cmin) of Pictilisib		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)	No
Secondary	Cmin of Paclitaxel		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)	No
Secondary	Cmin of Letrozole		Part 3: Predose (0h) on D1 of C1, C2-6, C=7, D15 of C1 (cycle length=28 days; up to 54.5 months)	No
Secondary	Area Under the Curve From Time Zero to Last Measurable Concentrations (AUClast) of Pictilisib	Parts 1 and 2 (dose escalation): predose (0 h) and 1,2,3,6 h postdose on D1 and D16 of C1, 24h postdose on D1 of C1; predose (0h) on D3,17 of C1; study completion (up to 55.5 months). Part 2 (dose expansion): predose (0h) and 1,2,3,6h postdose on D16 of C1; predose (0h) on D3, D17 of C1; study completion (up to 55.5 months). Part 3: 3h postdose on D1 of C1; 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)	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]	No
Secondary	AUClast of Paclitaxel	Parts 1 and 2 (dose escalation): pre-paclitaxel infusion (0 h), end of paclitaxel infusion (infusion length = 60 minutes), end of bevacizumab infusion (infusion length = 30 to 90 minutes), 2,4,6,24 h post-paclitaxel infusion on D2 and D16 of C1; study completion (up to 55.5 months). Part 2 (dose expansion): pre-paclitaxel infusion (0 h), end of paclitaxel infusion (infusion length = 60 minutes), end of bevacizumab infusion (infusion length = 30 to 90 minutes), 1,2,3,6,24 h post-paclitaxel infusion on D1 of C1; pre-paclitaxel infusion (0 h), end of paclitaxel infusion (infusion length = 60 minutes), end of bevacizumab infusion (infusion length = 30 to 90 minutes), 2, 4, 6, 24 h post-paclitaxel infusion on D16 of C1; study completion (cycle length=28 days; up to 55.5 months)	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]	No
Secondary	AUClast of Letrozole		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)	No
Secondary	Maximum Observed Plasma Concentration (Cmax) of Pictilisib	Parts 1 and 2 (dose escalation): predose (0 h) and 1,2,3,6 h postdose on D1 and D16 of C1, 24h postdose on D1 of C1; predose (0h) on D3,17 of C1; study completion (up to 55.5 months). Part 2 (dose expansion): predose (0h) and 1,2,3,6h postdose on D16 of C1; predose (0h) on D3, D17 of C1; study completion (up to 55.5 months). Part 3: 3h postdose on D1 of C1; 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)	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]	No
Secondary	Cmax of Paclitaxel	Parts 1 and 2 (dose escalation): pre-paclitaxel infusion (0 h), end of paclitaxel infusion (infusion length = 60 minutes), end of bevacizumab infusion (infusion length = 30 to 90 minutes), 2,4,6,24 h post-paclitaxel infusion on D2 and D16 of C1; study completion (up to 55.5 months). Part 2 (dose expansion): pre-paclitaxel infusion (0 h), end of paclitaxel infusion (infusion length = 60 minutes), end of bevacizumab infusion (infusion length = 30 to 90 minutes), 1,2,3,6,24 h post-paclitaxel infusion on D1 of C1; pre-paclitaxel infusion (0 h), end of paclitaxel infusion (infusion length = 60 minutes), end of bevacizumab infusion (infusion length = 30 to 90 minutes), 2, 4, 6, 24 h post-paclitaxel infusion on D16 of C1; study completion (cycle length=28 days; up to 55.5 months)	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]	No
Secondary	Cmax of Letrozole		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)	No
Secondary	Percentage of Participants With Objective Response According to Modified Response Evaluation Criteria in Solid Tumors (RECIST)		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])	No
Secondary	Duration of Response According to Modified RECIST		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])	No
Secondary	Percentage of Participants With Death or Disease Progression According to Modified RECIST		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])	No
Secondary	Progression-free Survival According to Modified RECIST		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])	No