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A Dose Escalation Study Evaluating the Safety and Tolerability of GDC-0032 in Participants With Locally Advanced or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma (NHL) and in Combination With Endocrine Therapy in Locally Advanced or Metastatic Hormone Receptor-Positive Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2017 by Genentech, Inc.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01296555
First received: February 14, 2011
Last updated: May 22, 2017
Last verified: May 2017
  Purpose
This is an open-label, multicenter, Phase I/II study to assess the safety, tolerability, and pharmacokinetics of GDC-0032. The Phase I portion will be divided into two stages. During Stage 1, GDC-0032 will be administered every day orally and at escalating doses in participants with locally advanced or metastatic solid tumors. During Stage 2, GDC-0032 will be administered alone or as combination therapy within indication-specific cohorts. In Phase II of the study, the efficacy and safety of the combination GDC-0032 and fulvestrant will be evaluated in post-menopausal female participants with locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative, hormone receptor-positive breast cancer.

Condition Intervention Phase
Solid Cancers
Non-Hodgkin's Lymphoma
Drug: Fulvestrant
Drug: GDC-0032
Drug: Letrozole
Drug: Midazolam
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: An Open-Label, Phase I/II, Dose-Escalation Study Evaluating the Safety and Tolerability of GDC-0032 in Patients With Locally Advanced or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma and in Combination With Endocrine Therapy in Patients With Locally Advanced or Metastatic Hormone Receptor-Positive Breast Cancer

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Phase I Stage I: Percentage of Participants With Adverse Events and Serious Adverse Events [ Time Frame: Baseline up to approximately 5 years ]
  • Phase 1 Stage 1: Percentage of Participants With Dose-Limiting Toxicities [ Time Frame: Baseline up to 35 days ]
  • Phase I Stage 1: Maximum Tolerated Dose of GDC-0032 [ Time Frame: Baseline up to 35 days ]
  • Phase I: Area Under the Concentration-Time Curve (AUC) From Zero to Infinity of GDC-0032 [ Time Frame: Baseline up to approximately 5 years (Detailed cohort-wise timeframe is given in the description) ]

    Detailed timeframe: Stage 1: Predose (0-2 hours [hr]), 0.5, 1, 2, 3, 4, 8, 24 (Days 1 and 15), 48, 72 hr (Day 1 only) postdose, Cycle 1; Predose (0-2 hr) on Days 8, 22, 29 of Cycle 1 and on Day 1 of each subsequent cycle up to Study Completion/Early Termination (approximately 5 years) (cycle length: 35 days for Cycle 1, 28 days for other cycles).

    Stage 2, Cohort A: Predose (0-2 hr);1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22;thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).

    Stage 2,Cohorts B, D, G: Predose (0-2 hr), 3 hr postdose on Cycle 1 Days 1, 15;Predose (0-2 hr) on Cycle 1 Days 8, 16;thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).

    Stage 2, Cohorts H, T, T2, X: Predose (0−4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days)


  • Phase I: AUC From Zero to tau (AUCtau) of GDC-0032 [ Time Frame: Baseline up to approximately 5 years (Detailed cohort-wise timeframe is given in the description) ]

    Detailed timeframe: Stage 1: Predose (0-2 hr), 0.5, 1, 2, 3, 4, 8, 24 (Days 1 and 15), 48, 72 hr (Day 1 only) postdose, Cycle 1; Predose (0-2 hr) on Days 8, 22, 29 of Cycle 1 and on Day 1 of each subsequent cycle up to Study Completion/Early Termination (approximately 5 years) (cycle length: 35 days for Cycle 1, 28 days for other cycles).

    Stage 2, Cohort A: Predose (0-2 hr); 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).

    Stage 2, Cohorts B, D, G: Predose (0-2 hr), 3 hr postdose on Cycle 1 Days 1, 15; Predose (0-2 hr) on Cycle 1 Days 8, 16; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).

    Stage 2, Cohorts H, T, T2, X: Predose (0−4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).


  • Phase I: Maximum Observed Concentration (Cmax) of GDC-0032 [ Time Frame: Baseline up to approximately 5 years (Detailed cohort-wise timeframe is given in the description) ]

    Detailed timeframe: Stage 1: Predose (0-2 hr), 0.5, 1, 2, 3, 4, 8, 24 (Days 1 and 15), 48, 72 hr (Day 1 only) postdose, Cycle 1; Predose (0-2 hr) on Days 8, 22, 29 of Cycle 1 and on Day 1 of each subsequent cycle up to Study Completion/Early Termination (approximately 5 years) (cycle length: 35 days for Cycle 1, 28 days for other cycles).

    Stage 2, Cohort A: Predose (0-2 hr); 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).

    Stage 2, Cohorts B, D, G: Predose (0-2 hr), 3 hr postdose on Cycle 1 Days 1, 15; Predose (0-2 hr) on Cycle 1 Days 8, 16; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).

    Stage 2, Cohorts H, T, T2, X: Predose (0−4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).


  • Phase I: Minimum Observed Concentration (Cmin) of GDC-0032 [ Time Frame: Baseline up to approximately 5 years (Detailed cohort-wise timeframe is given in the description) ]

    Detailed timeframe: Stage 1: Predose (0-2 hr), 0.5, 1, 2, 3, 4, 8, 24 (Days 1 and 15), 48, 72 hr (Day 1 only) postdose, Cycle 1; Predose (0-2 hr) on Days 8, 22, 29 of Cycle 1 and on Day 1 of each subsequent cycle up to Study Completion/Early Termination (approximately 5 years) (cycle length: 35 days for Cycle 1, 28 days for other cycles).

    Stage 2, Cohort A: Predose (0-2 hr); 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).

    Stage 2, Cohorts B, D, G: Predose (0-2 hr), 3 hr postdose on Cycle 1 Days 1, 15; Predose (0-2 hr) on Cycle 1 Days 8, 16; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).

    Stage 2, Cohorts H, T, T2, X: Predose (0−4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).


  • Phase I: Time to Reach Cmax (tmax) of GDC-0032 [ Time Frame: Baseline up to approximately 5 years (Detailed cohort-wise timeframe is given in the description) ]

    Detailed timeframe: Stage 1: Predose (0-2 hr), 0.5, 1, 2, 3, 4, 8, 24 (Days 1 and 15), 48, 72 hr (Day 1 only) postdose, Cycle 1; Predose (0-2 hr) on Days 8, 22, 29 of Cycle 1 and on Day 1 of each subsequent cycle up to Study Completion/Early Termination (approximately 5 years) (cycle length: 35 days for Cycle 1, 28 days for other cycles).

    Stage 2, Cohort A: Predose (0-2 hr); 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).

    Stage 2, Cohorts B, D, G: Predose (0-2 hr), 3 hr postdose on Cycle 1 Days 1, 15; Predose (0-2 hr) on Cycle 1 Days 8, 16; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).

    Stage 2, Cohorts H, T, T2, X: Predose (0−4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).


  • Phase I: Half-life (t1/2) of GDC-0032 [ Time Frame: Baseline up to approximately 5 years (Detailed cohort-wise timeframe is given in the description) ]

    Detailed timeframe: Stage 1: Predose (0-2 hr), 0.5, 1, 2, 3, 4, 8, 24 (Days 1 and 15), 48, 72 hr (Day 1 only) postdose, Cycle 1; Predose (0-2 hr) on Days 8, 22, 29 of Cycle 1 and on Day 1 of each subsequent cycle up to Study Completion/Early Termination (approximately 5 years) (cycle length: 35 days for Cycle 1, 28 days for other cycles).

    Stage 2, Cohort A: Predose (0-2 hr); 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).

    Stage 2, Cohorts B, D, G: Predose (0-2 hr), 3 hr postdose on Cycle 1 Days 1, 15; Predose (0-2 hr) on Cycle 1 Days 8, 16; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).

    Stage 2, Cohorts H, T, T2, X: Predose (0−4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).


  • Phase I: Apparent Clearance (CL/F) of GDC-0032 [ Time Frame: Baseline up to approximately 5 years (Detailed cohort-wise timeframe is given in the description) ]

    Detailed timeframe: Stage 1: Predose (0-2 hr), 0.5, 1, 2, 3, 4, 8, 24 (Days 1 and 15), 48, 72 hr (Day 1 only) postdose, Cycle 1; Predose (0-2 hr) on Days 8, 22, 29 of Cycle 1 and on Day 1 of each subsequent cycle up to Study Completion/Early Termination (approximately 5 years) (cycle length: 35 days for Cycle 1, 28 days for other cycles).

    Stage 2, Cohort A: Predose (0-2 hr); 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).

    Stage 2, Cohorts B, D, G: Predose (0-2 hr), 3 hr postdose on Cycle 1 Days 1, 15; Predose (0-2 hr) on Cycle 1 Days 8, 16; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).

    Stage 2, Cohorts H, T, T2, X: Predose (0−4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).


  • Phase I: Accumulation Ratio (AR) (Area Under the Concentration Time Curve at Steady-State Divided by Area Under the Concentration Time Curve for First Dose) of GDC-0032 [ Time Frame: Baseline up to approximately 5 years (Detailed cohort-wise timeframe is given in the description) ]

    Detailed timeframe: Stage 1: Predose (0-2 hr), 0.5, 1, 2, 3, 4, 8, 24 (Days 1 and 15), 48, 72 hr (Day 1 only) postdose, Cycle 1; Predose (0-2 hr) on Days 8, 22, 29 of Cycle 1 and on Day 1 of each subsequent cycle up to Study Completion/Early Termination (approximately 5 years) (cycle length: 35 days for Cycle 1, 28 days for other cycles).

    Stage 2, Cohort A: Predose (0-2 hr); 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).

    Stage 2, Cohorts B, D, G: Predose (0-2 hr), 3 hr postdose on Cycle 1 Days 1, 15; Predose (0-2 hr) on Cycle 1 Days 8, 16; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).

    Stage 2, Cohorts H, T, T2, X: Predose (0−4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).


  • Phase I: Recommended Dose of Single-Agent GDC-0032 [ Time Frame: Baseline up to 35 days ]
  • Phase II: Percentage of Participants With Clinical Benefit, as Assessed Using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 [ Time Frame: Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years) ]
  • Phase II: Percentage of Participants With Objective Response, as Assessed Using RECIST Version 1.1 [ Time Frame: Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years) ]

Secondary Outcome Measures:
  • Phase I: Fraction Dose Excreted (fe) of GDC-0032 [ Time Frame: Urine samples: Predose (0 hr), 0−6 hr and 6−24 hr after dosing on Day 1 of Cycle 1 (cycle length: 35 days) ]
  • Phase I: Renal Clearance (CLr) of GDC-0032 [ Time Frame: Urine samples: Predose (0 hr), 0−6 hr and 6−24 hr after dosing on Day 1 of Cycle 1 (cycle length: 35 days) ]
  • Phase I: Time to Achieve Steady State of GDC-0032 [ Time Frame: Baseline up to approximately 5 years (Detailed cohort-wise timeframe is given in the description) ]

    Detailed timeframe: Stage 1: Predose (0-2 hr), 0.5, 1, 2, 3, 4, 8, 24 (Days 1 and 15), 48, 72 hr (Day 1 only) postdose, Cycle 1; Predose (0-2 hr) on Days 8, 22, 29 of Cycle 1 and on Day 1 of each subsequent cycle up to Study Completion/Early Termination (approximately 5 years) (cycle length: 35 days for Cycle 1, 28 days for other cycles).

    Stage 2, Cohort A: Predose (0-2 hr); 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).

    Stage 2, Cohorts B, D, G: Predose (0-2 hr), 3 hr postdose on Cycle 1 Days 1, 15; Predose (0-2 hr) on Cycle 1 Days 8, 16; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).

    Stage 2, Cohorts H, T, T2, X: Predose (0−4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).


  • Phase I All Cohorts (Except Cohorts T and T2): Percentage of Participants With Best Overall Response, as Assessed Using RECIST Version 1.1 [ Time Frame: Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years) ]
  • Phase I All Cohorts (Except Cohorts T and T2): Duration of Objective Response, as Assessed Using RECIST Version 1.1 [ Time Frame: Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years) ]
  • Phase I All Cohorts (Except Cohorts T and T2): Progression Free Survival, as Assessed Using RECIST Version 1.1 [ Time Frame: Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years) ]
  • Phase I Cohort T: Percentage of Participants With Best Overall Response, as Assessed Using 2007 Revised International Working Group (IWG) Response Criteria in Malignant Lymphoma [ Time Frame: Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years) ]
  • Phase I Cohort T: Duration of Objective Response, as Assessed Using 2007 Revised IWG Response Criteria in Malignant Lymphoma [ Time Frame: Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years) ]
  • Phase I Cohort T: Progression Free Survival, as Assessed Using 2007 Revised IWG Response Criteria in Malignant Lymphoma [ Time Frame: Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years) ]
  • Phase I Cohort T2: Percentage of Participants With Best Overall Response, as Assessed Using Modified Version of 2014 Lugano Response Criteria in Malignant Lymphoma [ Time Frame: Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years) ]
  • Phase I Cohort T2: Duration of Objective Response, as Assessed Using Modified Version of 2014 Lugano Response Criteria in Malignant Lymphoma [ Time Frame: Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years) ]
  • Phase I Cohort T2: Progression Free Survival, as Assessed Using Modified Version of 2014 Lugano Response Criteria in Malignant Lymphoma [ Time Frame: Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years) ]
  • Phase I Stage 2 Food Effect: Cmax of GDC-0032 Under Fed Condition [ Time Frame: Stage 2, Cohort A: Predose (0-2 hr); 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days) ]
  • Phase I Stage 2 Food Effect: Cmax of GDC-0032 Under Fasted Condition [ Time Frame: Stage 2, Cohort A: Predose (0-2 hr); 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days) ]
  • Phase I Stage 2 Food Effect: AUC of GDC-0032 Under Fed Condition [ Time Frame: Stage 2, Cohort A: Predose (0-2 hr); 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days) ]
  • Phase I Stage 2 Food Effect: AUC of GDC-0032 Under Fasted Condition [ Time Frame: Stage 2, Cohort A: Predose (0-2 hr); 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days) ]
  • Phase I Stage 2 Cohort C: AUC from Time Zero to 24 Hours (AUC0-24) of Midazolam Prior to and After 14 Days Continuous GDC-0032 Dosing [ Time Frame: Predose (0-2 hr), 0.5, 1, 1.5, 2, 4, 8, 24 hours postdose on Cycle 1 Days 1 and 16 (Cycle length: 28 days) ]
  • Phase I Stage 2 Cohort C: Cmax of Midazolam Prior to and After 14 Days Continuous GDC-0032 Dosing [ Time Frame: Predose (0-2 hr), 0.5, 1, 1.5, 2, 4, 8, 24 hours postdose on Cycle 1 Days 1 and 16 (Cycle length: 28 days) ]
  • Phase I Stage 2 Cohort C: Tmax of Midazolam Prior to and After 14 Days Continuous GDC-0032 Dosing [ Time Frame: Predose (0-2 hr), 0.5, 1, 1.5, 2, 4, 8, 24 hours postdose on Cycle 1 Days 1 and 16 (Cycle length: 28 days) ]
  • Phase I Stage 2 Cohorts E, N, P, Q, R, S: AUC0-24 of Letrozole [ Time Frame: Baseline up to approximately 5 years (detailed timeframe is given in description) ]

    Detailed timeframe:

    Stage 2 Cohort E: Predose (0-2 hr) on Cycle 1 Day 1; Predose (0-2 hr), 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Day 15; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (up to approximately 5 years) (Cycle length: 28 days).

    Stage 2 Cohort N, P, Q, R: Predose (0−4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6 (Cycle length: 28 days).

    Stage 2 Cohort S: Predose (0−4 hr) on Day 1 of Cycle 2, 6 (Cycle length: 28 days).


  • Phase I Stage 2 Cohorts E, N, P, Q, R, S: Cmax of Letrozole [ Time Frame: Baseline up to approximately 5 years (detailed timeframe is given in description) ]

    Detailed timeframe:

    Stage 2 Cohort E: Predose (0-2 hr) on Cycle 1 Day 1; Predose (0-2 hr), 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Day 15; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (up to approximately 5 years) (Cycle length: 28 days).

    Stage 2 Cohort N, P, Q, R: Predose (0−4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6 (Cycle length: 28 days).

    Stage 2 Cohort S: Predose (0−4 hr) on Day 1 of Cycle 2, 6 (Cycle length: 28 days).


  • Phase I Stage 2 Cohorts E, N, P, Q, R, S: tmax of Letrozole [ Time Frame: Baseline up to approximately 5 years (detailed timeframe is given in description) ]

    Detailed timeframe:

    Stage 2 Cohort E: Predose (0-2 hr) on Cycle 1 Day 1; Predose (0-2 hr), 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Day 15; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (up to approximately 5 years) (Cycle length: 28 days).

    Stage 2 Cohort N, P, Q, R: Predose (0−4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6 (Cycle length: 28 days).

    Stage 2 Cohort S: Predose (0−4 hr) on Day 1 of Cycle 2, 6 (Cycle length: 28 days).


  • Phase I Stage 2 Cohorts F, J, K, L, M and Phase II: AUC0-24 of Fulvestrant [ Time Frame: Baseline up to approximately 5 years (detailed timeframe is given in description) ]

    Detailed timeframe:

    Stage 2 Cohort F: Predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (up to approximately 5 years) (Cycle length: 28 days).

    Stage 2 Cohorts J, K, M: Predose (0−4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6 (Cycle length: 28 days).

    Stage 2 Cohort L: Predose (0−4 hr) on Day 1 of Cycle 2, 6 (Cycle length: 28 days).

    Phase II: Predose (0−4 hr) on Day 1, 15 Cycle 1 and Day 1 of Cycles 2, 6 (Cycle length: 28 days).


  • Phase I Stage 2 Cohorts F, J, K, L, M and Phase II: Cmin of Fulvestrant [ Time Frame: Baseline up to approximately 5 years (detailed timeframe is given in description) ]

    Detailed timeframe:

    Stage 2 Cohort F: Predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (up to approximately 5 years) (Cycle length: 28 days).

    Stage 2 Cohorts J, K, M: Predose (0−4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6 (Cycle length: 28 days).

    Stage 2 Cohort L: Predose (0−4 hr) on Day 1 of Cycle 2, 6 (Cycle length: 28 days).

    Phase II: Predose (0−4 hr) on Day 1, 15 Cycle 1 and Day 1 of Cycles 2, 6 (Cycle length: 28 days).


  • Phase I Stage 2 Cohorts F, J, K, L, M and Phase II: tmax of Fulvestrant [ Time Frame: Baseline up to approximately 5 years (detailed timeframe is given in description) ]

    Detailed timeframe:

    Stage 2 Cohort F: Predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (up to approximately 5 years) (Cycle length: 28 days).

    Stage 2 Cohorts J, K, M: Predose (0−4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6 (Cycle length: 28 days).

    Stage 2 Cohort L: Predose (0−4 hr) on Day 1 of Cycle 2, 6 (Cycle length: 28 days).

    Phase II: Predose (0−4 hr) on Day 1, 15 Cycle 1 and Day 1 of Cycles 2, 6 (Cycle length: 28 days).


  • Phase I Stage 2 Cohort C: AUC0-24 of GDC-0032 in Combination with Midazolam [ Time Frame: Predose (0-2 hr), on Day 2, 16 Cycle 1; 0.5, 1,1.5, 2, 3, 4, 8, 24 hr post-dose on Day 16 Cycle 1; thereafter predose (0-2 hr) on Day 1 of each Cycles up to study completion/early termination (up to approximately 5 years) (cycle length: 28 days) ]
  • Phase I Stage 2 Cohort C: Cmax of GDC-0032 in Combination with Midazolam [ Time Frame: Predose (0-2 hr), on Day 2, 16 Cycle 1; 0.5, 1,1.5, 2, 3, 4, 8, 24 hr post-dose on Day 16 Cycle 1; thereafter predose (0-2 hr) on Day 1 of each Cycles up to study completion/early termination (up to approximately 5 years) (cycle length: 28 days) ]
  • Phase I Stage 2 Cohort C: Tmax of GDC-0032 in Combination with Midazolam [ Time Frame: Predose (0-2 hr), on Day 2, 16 Cycle 1; 0.5, 1,1.5, 2, 3, 4, 8, 24 hr post-dose on Day 16 Cycle 1; thereafter predose (0-2 hr) on Day 1 of each Cycles up to study completion/early termination (up to approximately 5 years) (cycle length: 28 days) ]
  • Phase I Stage 2 Cohorts E, N, P, Q, R, S: AUC0-24 of GDC-0032 in Combination with Letrozole [ Time Frame: Baseline up to approximately 5 years (detailed timeframe is given in description) ]

    Detailed timeframe:

    Stage 2 Cohort E: Predose (0-2 hr), 3 hr postdose on Cycle 1 Day 1; Predose (0-2 hr) on Cycle 1 Day 8; Predose (0-2 hr), 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Day 15; thereafter predose (0-2 hr) on Day 1 of each Cycle up to study completion/early termination (up to approximately 5 years) (Cycle length: 28 days).

    Stage 2 Cohort N, P, Q, R: Predose (0−4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).

    Stage 2 Cohort S: 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).


  • Phase I Stage 2 Cohorts E, N, P, Q, R, S: Cmax of GDC-0032 in Combination with Letrozole [ Time Frame: Baseline up to approximately 5 years (detailed timeframe is given in description) ]

    Detailed timeframe:

    Stage 2 Cohort E: Predose (0-2 hr), 3 hr postdose on Cycle 1 Day 1; Predose (0-2 hr) on Cycle 1 Day 8; Predose (0-2 hr), 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Day 15; thereafter predose (0-2 hr) on Day 1 of each Cycle up to study completion/early termination (up to approximately 5 years) (Cycle length: 28 days).

    Stage 2 Cohort N, P, Q, R: Predose (0−4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).

    Stage 2 Cohort S: 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).


  • Phase I Stage 2 Cohorts E, N, P, Q, R, S: Tmax of GDC-0032 in Combination with Letrozole [ Time Frame: Baseline up to approximately 5 years (detailed timeframe is given in description) ]

    Detailed timeframe:

    Stage 2 Cohort E: Predose (0-2 hr), 3 hr postdose on Cycle 1 Day 1; Predose (0-2 hr) on Cycle 1 Day 8; Predose (0-2 hr), 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Day 15; thereafter predose (0-2 hr) on Day 1 of each Cycle up to study completion/early termination (up to approximately 5 years) (Cycle length: 28 days).

    Stage 2 Cohort N, P, Q, R: Predose (0−4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).

    Stage 2 Cohort S: 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).


  • Phase I Stage 2 Cohorts F, J, K, L, M and Phase II: AUC0-24 of GDC-0032 in Combination with Fulvestrant [ Time Frame: Baseline up to approximately approximately 5 years (detailed timeframe is given in description) ]

    Detailed timeframe:

    Stage 2 Cohort F:Predose (0-2 hr), 3 hr postdose on Cycle 1 Day 1; Predose (0-2 hr) on Cycle 1 Day 8; Predose (0-2 hr), 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Day 15; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (up to approximately 5 years) (Cycle length: 28 days).

    Stage 2 Cohorts J, K, M: Predose(0−4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).

    Stage 2 Cohort L: 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).


  • Phase I Stage 2 Cohorts F, J, K, L, M and Phase II: Cmin of GDC-0032 Fulvestrant [ Time Frame: Baseline up to approximately approximately 5 years (detailed timeframe is given in description) ]

    Detailed timeframe:

    Stage 2 Cohort F:Predose (0-2 hr), 3 hr postdose on Cycle 1 Day 1; Predose (0-2 hr) on Cycle 1 Day 8; Predose (0-2 hr), 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Day 15; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (up to approximately 5 years) (Cycle length: 28 days).

    Stage 2 Cohorts J, K, M: Predose(0−4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).

    Stage 2 Cohort L: 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).


  • Phase I Stage 2 Cohorts F, J, K, L, M and Phase II: Tmax of GDC-0032 Fulvestrant [ Time Frame: Baseline up to approximately approximately 5 years (detailed timeframe is given in description) ]

    Detailed timeframe:

    Stage 2 Cohort F:Predose (0-2 hr), 3 hr postdose on Cycle 1 Day 1; Predose (0-2 hr) on Cycle 1 Day 8; Predose (0-2 hr), 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Day 15; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (up to approximately 5 years) (Cycle length: 28 days).

    Stage 2 Cohorts J, K, M: Predose(0−4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).

    Stage 2 Cohort L: 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).


  • Phase II: Duration of Objective Response, as Assessed Using RECIST Version 1.1 [ Time Frame: Baseline up to disease progression or death, whichever occurred first (up to approximately 5 years) ]
  • Phase II: Progression Free Survival, as Assessed Using RECIST Version 1.1 [ Time Frame: Baseline up to disease progression or death, whichever occurred first (up to approximately 5 years) ]
  • Overall Survival, as Assessed Using RECIST Version 1.1 [ Time Frame: Baseline up to death/study completion (up to approximately 5 years) ]
  • Phase II: Plasma Concentration of GDC-0032 [ Time Frame: Predose (0−4 hr) on Day 1, 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 4 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days) ]

Estimated Enrollment: 724
Actual Study Start Date: March 16, 2011
Estimated Study Completion Date: September 30, 2019
Estimated Primary Completion Date: September 30, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I, Stage 1: GDC-0032 as Single Agent
Participants with locally advanced or metastatic solid tumors will receive increasing doses of GDC-0032 administered orally daily in 28-day cycles. Dose escalation decisions will be based upon the observed incidence of DLTs.
Drug: GDC-0032
Participants will receive GDC-0032 at escalating (Phase I, Stage 1) or fixed (Phase II and Phase I, Stage 2) doses until disease progression. Cycle 1 may be 35 days in length to allow for a 7-day washout following the initial dose; thereafter, GDC-0032 will be administered orally once daily in 28-day cycles.
Experimental: Phase I, Stage 2: GDC-0032 + Fulvestrant
Participants (Cohorts F, J, K, L, and M) will receive GDC-0032 in combination with fulvestrant until disease progression.
Drug: Fulvestrant
Participants will receive fulvestrant 500 milligrams (mg) via intramuscular injection (as per package insert or Summary of Product Characteristics [SmPC]) on Days 1 and 15 of Cycle 1, then on Day 1 of each subsequent cycle, until disease progression (Cycle length: 28 days).
Other Name: Faslodex®
Drug: GDC-0032
Participants will receive GDC-0032 at escalating (Phase I, Stage 1) or fixed (Phase II and Phase I, Stage 2) doses until disease progression. Cycle 1 may be 35 days in length to allow for a 7-day washout following the initial dose; thereafter, GDC-0032 will be administered orally once daily in 28-day cycles.
Experimental: Phase I, Stage 2: GDC-0032 + Letrozole
Participants (Cohorts E, N, P, Q, R, and S) will receive GDC-0032 in combination with letrozole until disease progression.
Drug: GDC-0032
Participants will receive GDC-0032 at escalating (Phase I, Stage 1) or fixed (Phase II and Phase I, Stage 2) doses until disease progression. Cycle 1 may be 35 days in length to allow for a 7-day washout following the initial dose; thereafter, GDC-0032 will be administered orally once daily in 28-day cycles.
Drug: Letrozole
Participants will receive letrozole 2.5 mg orally (as per Package Insert or SmPC) once daily in 28-day cycles until disease progression.
Other Name: Femara®
Experimental: Phase I, Stage 2: GDC-0032 as Single Agent
Participants (Cohorts A, B, C, D, G, H, T, T2, and X) will receive GDC-0032 until disease progression.
Drug: GDC-0032
Participants will receive GDC-0032 at escalating (Phase I, Stage 1) or fixed (Phase II and Phase I, Stage 2) doses until disease progression. Cycle 1 may be 35 days in length to allow for a 7-day washout following the initial dose; thereafter, GDC-0032 will be administered orally once daily in 28-day cycles.
Experimental: Phase I, Stage 2: GDC-0032 + Midazolam
Participants (Cohort C) will receive GDC-0032 in combination with midazolam.
Drug: GDC-0032
Participants will receive GDC-0032 at escalating (Phase I, Stage 1) or fixed (Phase II and Phase I, Stage 2) doses until disease progression. Cycle 1 may be 35 days in length to allow for a 7-day washout following the initial dose; thereafter, GDC-0032 will be administered orally once daily in 28-day cycles.
Drug: Midazolam
Participants will receive midazolam 5 mg (as per Package Insert or SmPC) in hydrochloride syrup on Days 1 and 16 of Cycle 1.
Experimental: Phase II: GDC-0032 + Fulvestrant
Post-menopausal females with locally advanced or metastatic HER2-negative, hormone receptor-positive breast cancer will receive GDC-0032 in combination with fulvestrant until disease progression.
Drug: Fulvestrant
Participants will receive fulvestrant 500 milligrams (mg) via intramuscular injection (as per package insert or Summary of Product Characteristics [SmPC]) on Days 1 and 15 of Cycle 1, then on Day 1 of each subsequent cycle, until disease progression (Cycle length: 28 days).
Other Name: Faslodex®
Drug: GDC-0032
Participants will receive GDC-0032 at escalating (Phase I, Stage 1) or fixed (Phase II and Phase I, Stage 2) doses until disease progression. Cycle 1 may be 35 days in length to allow for a 7-day washout following the initial dose; thereafter, GDC-0032 will be administered orally once daily in 28-day cycles.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Phase I (Cohorts A through D, G, H, T, T2 and X): Histologically documented, locally advanced or metastatic solid malignancy or NHL that has progressed or failed to respond to at least one prior regimen and are not candidates for regimens known to provide clinical benefit
  • Phase I (Cohorts E and F): Post-menopausal females with locally advanced or metastatic hormone receptor-positive breast cancer that has progressed or failed to respond to at least one prior endocrine therapy in the adjuvant or metastatic setting
  • Phase I (Cohorts J through S): Post-menopausal females with HER2-negative, hormone-receptor positive breast cancer that has progressed or failed to response to at least one prior endocrine therapy in the adjuvant or metastatic setting
  • Phase II: Post-menopausal female participants with locally advanced or metastatic HER2-negative, hormone receptor-positive breast cancer
  • Phase I (Cohorts A through S) and Phase II: Evaluable or measurable disease per RECIST version 1.1
  • Phase I (Cohorts T, and T2): Greater than or equal to (>/=) 1 bi-dimensionally measurable lesion on computed tomography (CT) scan
  • Phase I (Cohort T): Participants with non-Hodgkin's lymphoma, regardless of PIK3CA mutation status
  • Phase 1 (Cohort T2): Participants with diffuse large B-cell lymphoma (DLBCL), regardless of PIK3CA mutation status
  • Phase I (Cohort X): Participants with PIK3CA-mutant tumors and measurable disease per RECIST v1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at Screening
  • Life expectancy of >/= 12 weeks
  • Adequate hematologic and organ function within 28 days prior to initiation of study treatment
  • Documented willingness to use an effective means of contraception for both men and women while participating in the study

Exclusion Criteria:

  • Known and untreated, or active central nervous system (CNS) metastases (progressing or requiring treatment)
  • Active congestive heart failure or ventricular arrhythmia requiring medication
  • Participants requiring any daily supplemental oxygen
  • Active inflammatory disease requiring immunosuppressants, including small or large intestinal inflammation such as Crohn's disease or ulcerative colitis
  • Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
  • Treatment with chemotherapy less than or equal to (</=) 3 weeks before study treatment
  • Oral endocrine therapy </= 2 weeks before study treatment
  • Treatment with investigational drug </= 3 weeks or 5 half-lives before study treatment
  • Treatment with biologic therapy </= 3 weeks before study treatment
  • Treatment with kinase inhibitors </= 2 weeks before study treatment
  • Radiation therapy (other than radiation to bony metastases) as cancer therapy </= 4 weeks before study treatment
  • Palliative radiation therapy to bony metastases </= 2 weeks before study treatment
  • Major surgery </= 4 weeks before study treatment
  • Any other diseases, active or uncontrolled pulmonary dysfunction, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that may affect the interpretation of the results, or renders the participant at high risk from treatment complications (examples include but are not limited to clinically significant non-healing wound, active bleeding, or ongoing fistula or active tuberculosis infection)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01296555

Contacts
Contact: Reference Study ID Number: PMT4979g www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

  Show 34 Study Locations
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Genentech, Inc.
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01296555     History of Changes
Other Study ID Numbers: PMT4979g
GO00886 ( Other Identifier: Hoffmann-La Roche )
2012-002042-21 ( EudraCT Number )
Study First Received: February 14, 2011
Last Updated: May 22, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Midazolam
Hormones
Estradiol
Fulvestrant
Letrozole
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on May 23, 2017