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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.
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Verified July 2017 by Genentech, Inc.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01296555
First received: February 14, 2011
Last updated: July 14, 2017
Last verified: July 2017
February 14, 2011
July 14, 2017
March 16, 2011
September 29, 2019   (Final data collection date for primary outcome measure)
  • 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) ]
  • Incidence of adverse events by NCI CTCAE v4.0 grade and associated dose of GDC-0032 [ Time Frame: Up to 2 years ]
  • Incidence of dose-limiting toxicities (DLTs) by NCI CTCAE v4.0 grade and associated dose of GDC-0032 [ Time Frame: Days 1-35 ]
  • Incidence of Grade 3 and 4 abnormalities in safety-related laboratory parameters and associated dose of GDC-0032 [ Time Frame: Up to 2 years ]
Complete list of historical versions of study NCT01296555 on ClinicalTrials.gov Archive Site
  • 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) ]
  • Best overall response for patients with measurable disease according to RECIST v1.1 [ Time Frame: Up to 2 years ]
  • Duration of objective response for patients with measurable disease according to RECIST v1.1 [ Time Frame: Up to 2 years ]
  • Progression free survival (PFS) for patients with measurable disease according to RECIST v1.1 [ Time Frame: Up to 2 years ]
Not Provided
Not Provided
 
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
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
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.
Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Solid Cancers
  • Non-Hodgkin's Lymphoma
  • 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.
  • 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®
  • 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 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.
    Intervention: Drug: GDC-0032
  • 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.
    Interventions:
    • Drug: Fulvestrant
    • Drug: GDC-0032
  • 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.
    Interventions:
    • Drug: GDC-0032
    • Drug: Letrozole
  • 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.
    Intervention: Drug: GDC-0032
  • Experimental: Phase I, Stage 2: GDC-0032 + Midazolam
    Participants (Cohort C) will receive GDC-0032 in combination with midazolam.
    Interventions:
    • Drug: GDC-0032
    • Drug: Midazolam
  • 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.
    Interventions:
    • Drug: Fulvestrant
    • Drug: GDC-0032
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
724
September 29, 2019
September 29, 2019   (Final data collection date for primary outcome measure)

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)
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
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
Canada,   France,   Spain,   United States
 
 
NCT01296555
PMT4979g
GO00886 ( Other Identifier: Hoffmann-La Roche )
2012-002042-21 ( EudraCT Number )
Not Provided
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
Genentech, Inc.
Genentech, Inc.
Not Provided
Study Director: Clinical Trials Genentech, Inc.
Genentech, Inc.
July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP