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

• Register: ClinicalTrials.gov
• Last refreshed on: 13 September 2021
• Main ID: NCT01296555
• Date of registration: 14/02/2011
• Prospective Registration: Yes
• Primary sponsor: Genentech, Inc.
• Public 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
• Scientific 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
• Date of first enrolment: March 16, 2011
• Target sample size: 686
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01296555
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Canada, France, Spain, United States

Contacts

• Name: Clinical Trials
• Affiliation: Genentech, Inc.

Key inclusion & exclusion 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 (
- Oral endocrine therapy
- Treatment with investigational drug
- Treatment with biologic therapy
- Treatment with kinase inhibitors
- Radiation therapy (other than radiation to bony metastases) as cancer therapy weeks before study treatment

- Palliative radiation therapy to bony metastases
- Major surgery
- 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)



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Non-Hodgkin's Lymphoma

Solid Cancers

Intervention(s)

Drug: GDC-0032

Drug: Midazolam

Drug: Fulvestrant

Drug: Letrozole

Primary Outcome(s)

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)]

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)]

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

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)]

Phase I: Recommended Dose of Single-Agent 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)]

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)]

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 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)]

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 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)]

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)]

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)]

Secondary Outcome(s)

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: 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 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: 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 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)]

Overall Survival, as Assessed Using RECIST Version 1.1 [Time Frame: Baseline up to death/study completion (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 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)]

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 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)]

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)]

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 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 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 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)]

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 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)]

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 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)]

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)]

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)]

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 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)]

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 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)]

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 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)]

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 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)]

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 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 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)]

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 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)]

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 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: 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)]

Secondary ID(s)

GO00886

2012-002042-21

PMT4979g

Source(s) of Monetary Support

Please refer to primary and secondary sponsors