Clinical Trial: NCT01296555 - My Cancer Genome

NCT01296555

Description:

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.

Related Conditions:

Breast Carcinoma
Malignant Solid Tumor
Non-Hodgkin Lymphoma

Recruiting Status:

Active, not recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT01296555

Trial Eligibility

Document

Title

Brief Title: 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
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

Clinical Trial IDs

ORG STUDY ID: PMT4979g
SECONDARY ID: GO00886
SECONDARY ID: 2012-002042-21
NCT ID: NCT01296555

Conditions

Solid Cancers
Non-Hodgkin's Lymphoma

Interventions

Drug	Synonyms	Arms
Fulvestrant	Faslodex®	Phase I, Stage 2: GDC-0032 + Fulvestrant
GDC-0032		Phase I, Stage 1: GDC-0032 as Single Agent
Letrozole	Femara®	Phase I, Stage 2: GDC-0032 + Letrozole
Midazolam		Phase I, Stage 2: GDC-0032 + Midazolam

Purpose

Trial Arms

Name	Type	Description	Interventions
Phase I, Stage 1: GDC-0032 as Single Agent	Experimental	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.	GDC-0032
Phase I, Stage 2: GDC-0032 + Fulvestrant	Experimental	Participants (Cohorts F, J, K, L, and M) will receive GDC-0032 in combination with fulvestrant until disease progression.	Fulvestrant GDC-0032
Phase I, Stage 2: GDC-0032 + Letrozole	Experimental	Participants (Cohorts E, N, P, Q, R, and S) will receive GDC-0032 in combination with letrozole until disease progression.	GDC-0032 Letrozole
Phase I, Stage 2: GDC-0032 as Single Agent	Experimental	Participants (Cohorts A, B, C, D, G, H, T, T2, and X) will receive GDC-0032 until disease progression.	GDC-0032
Phase I, Stage 2: GDC-0032 + Midazolam	Experimental	Participants (Cohort C) will receive GDC-0032 in combination with midazolam.	GDC-0032 Midazolam
Phase II: GDC-0032 + Fulvestrant	Experimental	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.	Fulvestrant GDC-0032

Eligibility 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)

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Phase I Stage I: Percentage of Participants With Adverse Events and Serious Adverse Events
Time Frame:	Baseline up to approximately 5 years
Safety Issue:
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)

Secondary Outcome Measures

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
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).

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
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).

Measure:	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)
Safety Issue:
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).

Measure:	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)
Safety Issue:
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).

Measure:	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)
Safety Issue:
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).

Measure:	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)
Safety Issue:
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).

Measure:	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)
Safety Issue:
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).

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
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).

Measure:	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)
Safety Issue:
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).

Measure:	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)
Safety Issue:
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).

Measure:	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)
Safety Issue:
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).

Measure:	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)
Safety Issue:
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).

Measure:	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)
Safety Issue:
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).

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	Overall Survival, as Assessed Using RECIST Version 1.1
Time Frame:	Baseline up to death/study completion (up to approximately 5 years)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Details

Phase:	Phase 1
Primary Purpose:	Interventional
Overall Status:	Active, not recruiting
Lead Sponsor:	Genentech, Inc.

Last Updated

June 11, 2021

Clinical Trials /

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