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

NCT ID: NCT01296555

Last Updated: 2024-07-31

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 674 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-16
• Study Completion Date: 2021-06-25

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.

Conditions

Solid Cancers; Non-Hodgkin's Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

GDC-0032

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Fulvestrant

Intervention Type: DRUG

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).

GDC-0032

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

GDC-0032

Intervention Type: DRUG

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.

Letrozole

Intervention Type: DRUG

Participants will receive letrozole 2.5 mg orally (as per Package Insert or SmPC) once daily in 28-day cycles until disease progression.

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.

Group Type: EXPERIMENTAL

GDC-0032

Intervention Type: DRUG

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.

Phase I, Stage 2: GDC-0032 + Midazolam

Participants (Cohort C) will receive GDC-0032 in combination with midazolam.

Group Type: EXPERIMENTAL

GDC-0032

Intervention Type: DRUG

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.

Midazolam

Intervention Type: DRUG

Participants will receive midazolam 5 mg (as per Package Insert or SmPC) in hydrochloride syrup on Days 1 and 16 of Cycle 1.

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.

Group Type: EXPERIMENTAL

Fulvestrant

Intervention Type: DRUG

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).

GDC-0032

Intervention Type: DRUG

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.

Interventions

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).

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Faslodex®; Femara®

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Genentech, Inc.

Locations

TGen Clinical Research Srvs

Scottsdale, Arizona, United States

University of Arizona Cancer Center

Tucson, Arizona, United States

University of California Irvine Medical Center

Orange, California, United States

UC Davis; Comprehensive Cancer Center

Sacramento, California, United States

Sutter Health

San Francisco, California, United States

Yale University

New Haven, Connecticut, United States

Florida Cancer Specialists - Fort Myers (New Hampshire Ct)

Fort Myers, Florida, United States

Sarah Cannon Res Inst; FL

Sarasota, Florida, United States

Univ of Chicago

Chicago, Illinois, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Maine, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Dana Farber Cancer Inst.

Boston, Massachusetts, United States

Washington University; Division of Oncology

St Louis, Missouri, United States

New York Oncology Hematology, P.C.

Albany, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Sarah Cannon Res Inst; OK

Oklahoma City, Oklahoma, United States

West Cancer Center

Germantown, Tennessee, United States

Sarah Cannon Res Inst; TN Onc

Nashville, Tennessee, United States

Vanderbilt Breast Center; Vanderbilt Health Pharmacy

Nashville, Tennessee, United States

Vanderbilt

Nashville, Tennessee, United States

Texas Cancer Center

Abilene, Texas, United States

Mary Crowley Cancer Rsch Ctr

Dallas, Texas, United States

Baylor Sammons Cancer Center

Dallas, Texas, United States

MD Anderson Cancer Center

Houston, Texas, United States

USO - Tyler Cancer Ctr

Tyler, Texas, United States

Northwest Cancer Specialists - Vancouver

Vancouver, Washington, United States

Yakima Valley Memorial Hospital/North Star Lodge

Yakima, Washington, United States

University Health Network; Princess Margaret Hospital; Medical Oncology Dept

Toronto, Ontario, Canada

Institut Gustave Roussy

Villejuif, , France

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Sant Andreu de la Barca, Barcelona, Spain

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Countries

United States; Canada; France; Spain

References

Moein A, Jin JY, Wright MR, Wong H. Quantitative characterization of the effects of fulvestrant alone or in combination with taselisib (PI3Kinase inhibitor) on longitudinal tumor growth in patients with estrogen receptor-positive, HER2-negative, PIK3CA-mutant, advanced or metastatic breast cancer. Cancer Chemother Pharmacol. 2024 Sep;94(3):421-436. doi: 10.1007/s00280-024-04690-4. Epub 2024 Jun 27.

Reference Type: DERIVED

PMID: 38937298 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

GO00886

Identifier Type: OTHER

Identifier Source: secondary_id

2012-002042-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PMT4979g

Identifier Type: -

Identifier Source: org_study_id