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

Sponsor
Genentech, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01296555
Collaborator
(none)
686
31
6
123.3
22.1
0.2

Study Details

Study Description

Brief Summary

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 or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
686 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
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
Actual Study Start Date :
Mar 16, 2011
Actual Primary Completion Date :
Jun 25, 2021
Actual Study Completion Date :
Jun 25, 2021

Arms and Interventions

Arm Intervention/Treatment
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 Names:
  • 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 Names:
  • 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 Names:
  • 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.

    Outcome Measures

    Primary Outcome Measures

    1. Phase I Stage I: Percentage of Participants With Adverse Events and Serious Adverse Events [Baseline up to approximately 5 years]

    2. Phase 1 Stage 1: Percentage of Participants With Dose-Limiting Toxicities [Baseline up to 35 days]

    3. Phase I Stage 1: Maximum Tolerated Dose of GDC-0032 [Baseline up to 35 days]

    4. Phase I: Area Under the Concentration-Time Curve (AUC) From Zero to Infinity of GDC-0032 [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)

    5. Phase I: AUC From Zero to tau (AUCtau) of GDC-0032 [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).

    6. Phase I: Maximum Observed Concentration (Cmax) of GDC-0032 [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).

    7. Phase I: Minimum Observed Concentration (Cmin) of GDC-0032 [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).

    8. Phase I: Time to Reach Cmax (tmax) of GDC-0032 [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).

    9. Phase I: Half-life (t1/2) of GDC-0032 [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).

    10. Phase I: Apparent Clearance (CL/F) of GDC-0032 [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).

    11. 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 [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).

    12. Phase I: Recommended Dose of Single-Agent GDC-0032 [Baseline up to 35 days]

    13. Phase II: Percentage of Participants With Clinical Benefit, as Assessed Using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 [Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)]

    14. Phase II: Percentage of Participants With Objective Response, as Assessed Using RECIST Version 1.1 [Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)]

    Secondary Outcome Measures

    1. Phase I: Fraction Dose Excreted (fe) of GDC-0032 [Urine samples: Predose (0 hr), 0-6 hr and 6-24 hr after dosing on Day 1 of Cycle 1 (cycle length: 35 days)]

    2. Phase I: Renal Clearance (CLr) of GDC-0032 [Urine samples: Predose (0 hr), 0-6 hr and 6-24 hr after dosing on Day 1 of Cycle 1 (cycle length: 35 days)]

    3. Phase I: Time to Achieve Steady State of GDC-0032 [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).

    4. Phase I All Cohorts (Except Cohorts T and T2): Percentage of Participants With Best Overall Response, as Assessed Using RECIST Version 1.1 [Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)]

    5. Phase I All Cohorts (Except Cohorts T and T2): Duration of Objective Response, as Assessed Using RECIST Version 1.1 [Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)]

    6. Phase I All Cohorts (Except Cohorts T and T2): Progression Free Survival, as Assessed Using RECIST Version 1.1 [Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)]

    7. 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 [Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)]

    8. Phase I Cohort T: Duration of Objective Response, as Assessed Using 2007 Revised IWG Response Criteria in Malignant Lymphoma [Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)]

    9. Phase I Cohort T: Progression Free Survival, as Assessed Using 2007 Revised IWG Response Criteria in Malignant Lymphoma [Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)]

    10. Phase I Cohort T2: Percentage of Participants With Best Overall Response, as Assessed Using Modified Version of 2014 Lugano Response Criteria in Malignant Lymphoma [Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)]

    11. Phase I Cohort T2: Duration of Objective Response, as Assessed Using Modified Version of 2014 Lugano Response Criteria in Malignant Lymphoma [Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)]

    12. Phase I Cohort T2: Progression Free Survival, as Assessed Using Modified Version of 2014 Lugano Response Criteria in Malignant Lymphoma [Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)]

    13. Phase I Stage 2 Food Effect: Cmax of GDC-0032 Under Fed Condition [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)]

    14. Phase I Stage 2 Food Effect: Cmax of GDC-0032 Under Fasted Condition [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)]

    15. Phase I Stage 2 Food Effect: AUC of GDC-0032 Under Fed Condition [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)]

    16. Phase I Stage 2 Food Effect: AUC of GDC-0032 Under Fasted Condition [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)]

    17. 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 [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)]

    18. Phase I Stage 2 Cohort C: Cmax of Midazolam Prior to and After 14 Days Continuous GDC-0032 Dosing [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)]

    19. Phase I Stage 2 Cohort C: Tmax of Midazolam Prior to and After 14 Days Continuous GDC-0032 Dosing [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)]

    20. Phase I Stage 2 Cohorts E, N, P, Q, R, S: AUC0-24 of Letrozole [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).

    21. Phase I Stage 2 Cohorts E, N, P, Q, R, S: Cmax of Letrozole [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).

    22. Phase I Stage 2 Cohorts E, N, P, Q, R, S: tmax of Letrozole [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).

    23. Phase I Stage 2 Cohorts F, J, K, L, M and Phase II: AUC0-24 of Fulvestrant [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).

    24. Phase I Stage 2 Cohorts F, J, K, L, M and Phase II: Cmin of Fulvestrant [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).

    25. Phase I Stage 2 Cohorts F, J, K, L, M and Phase II: tmax of Fulvestrant [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).

    26. Phase I Stage 2 Cohort C: AUC0-24 of GDC-0032 in Combination with Midazolam [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)]

    27. Phase I Stage 2 Cohort C: Cmax of GDC-0032 in Combination with Midazolam [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)]

    28. Phase I Stage 2 Cohort C: Tmax of GDC-0032 in Combination with Midazolam [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)]

    29. Phase I Stage 2 Cohorts E, N, P, Q, R, S: AUC0-24 of GDC-0032 in Combination with Letrozole [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).

    30. Phase I Stage 2 Cohorts E, N, P, Q, R, S: Cmax of GDC-0032 in Combination with Letrozole [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).

    31. Phase I Stage 2 Cohorts E, N, P, Q, R, S: Tmax of GDC-0032 in Combination with Letrozole [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).

    32. Phase I Stage 2 Cohorts F, J, K, L, M and Phase II: AUC0-24 of GDC-0032 in Combination with Fulvestrant [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).

    33. Phase I Stage 2 Cohorts F, J, K, L, M and Phase II: Cmin of GDC-0032 Fulvestrant [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).

    34. Phase I Stage 2 Cohorts F, J, K, L, M and Phase II: Tmax of GDC-0032 Fulvestrant [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).

    35. Phase II: Duration of Objective Response, as Assessed Using RECIST Version 1.1 [Baseline up to disease progression or death, whichever occurred first (up to approximately 5 years)]

    36. Phase II: Progression Free Survival, as Assessed Using RECIST Version 1.1 [Baseline up to disease progression or death, whichever occurred first (up to approximately 5 years)]

    37. Overall Survival, as Assessed Using RECIST Version 1.1 [Baseline up to death/study completion (up to approximately 5 years)]

    38. Phase II: Plasma Concentration of GDC-0032 [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)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 TGen Clinical Research Srvs Scottsdale Arizona United States 85258
    2 University of Arizona Cancer Center Tucson Arizona United States 85719
    3 University of California Irvine Medical Center Orange California United States 92868
    4 UC Davis; Comprehensive Cancer Center Sacramento California United States 95817
    5 Sutter Health San Francisco California United States 94109
    6 Yale University New Haven Connecticut United States 06510
    7 Florida Cancer Specialists - Fort Myers (New Hampshire Ct) Fort Myers Florida United States 33901-8101
    8 Sarah Cannon Res Inst; FL Sarasota Florida United States 34232
    9 Univ of Chicago Chicago Illinois United States 60637
    10 Massachusetts General Hospital Cancer Center Boston Massachusetts United States 02114
    11 Dana Farber Cancer Inst. Boston Massachusetts United States 02115
    12 Barbara Ann Karmanos Cancer Institute Detroit Michigan United States 48201
    13 Washington University; Division of Oncology Saint Louis Missouri United States 63110
    14 New York Oncology Hematology, P.C. Albany New York United States 12206
    15 Memorial Sloan-Kettering Cancer Center New York New York United States 10065
    16 Sarah Cannon Res Inst; OK Oklahoma City Oklahoma United States 73104
    17 West Cancer Center Germantown Tennessee United States 38138
    18 Sarah Cannon Res Inst; TN Onc Nashville Tennessee United States 37203
    19 Vanderbilt Breast Center; Vanderbilt Health Pharmacy Nashville Tennessee United States 37204
    20 Vanderbilt Nashville Tennessee United States 37232
    21 Texas Cancer Center Abilene Texas United States 79606-5208
    22 Mary Crowley Cancer Rsch Ctr Dallas Texas United States 75230
    23 Baylor Sammons Cancer Center Dallas Texas United States 75246
    24 MD Anderson Cancer Center Houston Texas United States 77030
    25 USO - Tyler Cancer Ctr Tyler Texas United States 75702
    26 Northwest Cancer Specialists - Vancouver Vancouver Washington United States 98684
    27 Yakima Valley Memorial Hospital/North Star Lodge Yakima Washington United States 98902
    28 University Health Network; Princess Margaret Hospital; Medical Oncology Dept Toronto Ontario Canada M5G 2M9
    29 Institut Gustave Roussy Villejuif France 94805
    30 Hospital Univ Vall d'Hebron; Servicio de Oncologia Barcelona Spain 08035
    31 Hospital Clinico Universitario de Valencia Valencia Spain 46010

    Sponsors and Collaborators

    • Genentech, Inc.

    Investigators

    • Study Director: Clinical Trials, Genentech, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Genentech, Inc.
    ClinicalTrials.gov Identifier:
    NCT01296555
    Other Study ID Numbers:
    • PMT4979g
    • GO00886
    • 2012-002042-21
    First Posted:
    Feb 15, 2011
    Last Update Posted:
    Sep 5, 2021
    Last Verified:
    Sep 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Sep 5, 2021