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

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 Tumours or Non-Hodgkin's Lymphoma and in Combination With Endocrine Therapy in Patients With Locally Advanced or Metastatic Hormone Receptor-Positive Breast Cancer

Summary:

This is an open-label, multicentre, 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 tumours. 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.

Trial Description

Primary Outcome:

  • Phase I Stage I: Percentage of Participants With Adverse Events and Serious Adverse Events
  • Phase 1 Stage 1: Percentage of Participants With Dose-Limiting Toxicities
  • Phase I Stage 1: Maximum Tolerated Dose of GDC-0032
  • Phase I: Area Under the Concentration-Time Curve (AUC) From Zero to Infinity of GDC-0032
  • Phase I: AUC From Zero to tau (AUCtau) of GDC-0032
  • Phase I: Maximum Observed Concentration (Cmax) of GDC-0032
  • Phase I: Minimum Observed Concentration (Cmin) of GDC-0032
  • Phase I: Time to Reach Cmax (tmax) of GDC-0032
  • Phase I: Half-life (t1/2) of GDC-0032
  • Phase I: Apparent Clearance (CL/F) of GDC-0032
  • 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
  • Phase I: Recommended Dose of Single-Agent GDC-0032
  • Phase II: Percentage of Participants With Clinical Benefit, as Assessed Using Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1
  • Phase II: Percentage of Participants With Objective Response, as Assessed Using RECIST Version 1.1
Secondary Outcome:
  • Phase I: Fraction Dose Excreted (fe) of GDC-0032
  • Phase I: Renal Clearance (CLr) of GDC-0032
  • Phase I: Time to Achieve Steady State of GDC-0032
  • Phase I All Cohorts (Except Cohorts T and T2): Percentage of Participants With Best Overall Response, as Assessed Using RECIST Version 1.1
  • Phase I All Cohorts (Except Cohorts T and T2): Duration of Objective Response, as Assessed Using RECIST Version 1.1
  • Phase I All Cohorts (Except Cohorts T and T2): Progression Free Survival, as Assessed Using RECIST Version 1.1
  • 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
  • Phase I Cohort T: Duration of Objective Response, as Assessed Using 2007 Revised IWG Response Criteria in Malignant Lymphoma
  • Phase I Cohort T: Progression Free Survival, as Assessed Using 2007 Revised IWG Response Criteria in Malignant Lymphoma
  • Phase I Cohort T2: Percentage of Participants With Best Overall Response, as Assessed Using Modified Version of 2014 Lugano Response Criteria in Malignant Lymphoma
  • Phase I Cohort T2: Duration of Objective Response, as Assessed Using Modified Version of 2014 Lugano Response Criteria in Malignant Lymphoma
  • Phase I Cohort T2: Progression Free Survival, as Assessed Using Modified Version of 2014 Lugano Response Criteria in Malignant Lymphoma
  • Phase I Stage 2 Food Effect: Cmax of GDC-0032 Under Fed Condition
  • Phase I Stage 2 Food Effect: Cmax of GDC-0032 Under Fasted Condition
  • Phase I Stage 2 Food Effect: AUC of GDC-0032 Under Fed Condition
  • Phase I Stage 2 Food Effect: AUC of GDC-0032 Under Fasted Condition
  • 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
  • Phase I Stage 2 Cohort C: Cmax of Midazolam Prior to and After 14 Days Continuous GDC-0032 Dosing
  • Phase I Stage 2 Cohort C: Tmax of Midazolam Prior to and After 14 Days Continuous GDC-0032 Dosing
  • Phase I Stage 2 Cohorts E, N, P, Q, R, S: AUC0-24 of Letrozole
  • Phase I Stage 2 Cohorts E, N, P, Q, R, S: Cmax of Letrozole
  • Phase I Stage 2 Cohorts E, N, P, Q, R, S: tmax of Letrozole
  • Phase I Stage 2 Cohorts F, J, K, L, M and Phase II: AUC0-24 of Fulvestrant
  • Phase I Stage 2 Cohorts F, J, K, L, M and Phase II: Cmin of Fulvestrant
  • Phase I Stage 2 Cohorts F, J, K, L, M and Phase II: tmax of Fulvestrant
  • Phase I Stage 2 Cohort C: AUC0-24 of GDC-0032 in Combination with Midazolam
  • Phase I Stage 2 Cohort C: Cmax of GDC-0032 in Combination with Midazolam
  • Phase I Stage 2 Cohort C: Tmax of GDC-0032 in Combination with Midazolam
  • Phase I Stage 2 Cohorts E, N, P, Q, R, S: AUC0-24 of GDC-0032 in Combination with Letrozole
  • Phase I Stage 2 Cohorts E, N, P, Q, R, S: Cmax of GDC-0032 in Combination with Letrozole
  • Phase I Stage 2 Cohorts E, N, P, Q, R, S: Tmax of GDC-0032 in Combination with Letrozole
  • Phase I Stage 2 Cohorts F, J, K, L, M and Phase II: AUC0-24 of GDC-0032 in Combination with Fulvestrant
  • Phase I Stage 2 Cohorts F, J, K, L, M and Phase II: Cmin of GDC-0032 Fulvestrant
  • Phase I Stage 2 Cohorts F, J, K, L, M and Phase II: Tmax of GDC-0032 Fulvestrant
  • Phase II: Duration of Objective Response, as Assessed Using RECIST Version 1.1
  • Phase II: Progression Free Survival, as Assessed Using RECIST Version 1.1
  • Overall Survival, as Assessed Using RECIST Version 1.1
  • Phase II: Plasma Concentration of GDC-0032

View this trial on ClinicalTrials.gov

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Resources

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