Trial record 1 of 14 for:    gdc0032
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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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by Genentech, Inc.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01296555
First received: February 14, 2011
Last updated: July 1, 2016
Last verified: July 2016
  Purpose
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 (PO) 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 Intervention Phase
Non-Hodgkin's Lymphoma, Solid Cancers
Drug: Fulvestrant
Drug: GDC-0032
Drug: Letrozole
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Area under the concentration-time curve (AUC) of GDC-0032 [ Time Frame: Pre-dose and/or post-dose on Days 1, 2, 3, 4, 8, 9, 15, 16, 22, 23, and 29 of Cycle 1, then on Day 1 of each subsequent cycle ] [ Designated as safety issue: No ]
  • Minimum observed concentration (Cmin) of GDC-0032 [ Time Frame: Pre-dose and/or post-dose on Days 1, 2, 3, 4, 8, 9, 15, 16, 22, 23, and 29 of Cycle 1, then on Day 1 of each subsequent cycle ] [ Designated as safety issue: No ]
  • Maximum observed concentration (Cmax) of GDC-0032 [ Time Frame: Pre-dose and/or post-dose on Days 1, 2, 3, 4, 8, 9, 15, 16, 22, 23, and 29 of Cycle 1, then on Day 1 of each subsequent cycle ] [ Designated as safety issue: No ]
  • Incidence of adverse events by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4.0) grade and associated dose of GDC-0032 [ Time Frame: Up to approximately 3 years ] [ Designated as safety issue: No ]
  • Incidence of dose-limiting toxicities (DLTs) by NCI CTCAE v4.0 grade and associated dose of GDC-0032 [ Time Frame: Up to 35 days ] [ Designated as safety issue: No ]
  • Incidence of Grade 3 and 4 abnormalities in safety-related laboratory parameters and associated dose of GDC-0032 [ Time Frame: Up to approximately 3 years ] [ Designated as safety issue: No ]
  • Phase II: Clinical benefit rate with the combination GDC-0032 + fulvestrant [ Time Frame: Up to approximately 3 years ] [ Designated as safety issue: No ]
  • Phase II: Objective response rate with the combination GDC-0032 + fulvestrant [ Time Frame: Up to approximately 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Phase I: Best overall response [ Time Frame: Up to approximately 3 years ] [ Designated as safety issue: No ]
  • Phase I: Duration of objective response [ Time Frame: Up to approximately 3 years ] [ Designated as safety issue: No ]
  • Phase I: Progression-free survival (PFS) [ Time Frame: Up to approximately 3 years ] [ Designated as safety issue: No ]
  • Phase II: Duration of response with the combination GDC-0032 + fulvestrant [ Time Frame: Up to approximately 3 years ] [ Designated as safety issue: No ]
  • Phase II: PFS with the combination GDC-0032 + fulvestrant [ Time Frame: Up to approximately 3 years ] [ Designated as safety issue: No ]
  • Phase II: Overall survival with the combination GDC-0032 + fulvestrant [ Time Frame: Up to approximately 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 724
Study Start Date: March 2011
Estimated Study Completion Date: September 2019
Estimated Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 PO 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 PO once daily in 28-day cycles.
Experimental: Phase I, Stage 2: GDC-0032 + Fulvestrant
Select indication-specific cohorts (F, J, K, L, and M) will receive GDC-0032 administered PO in combination with fulvestrant until disease progression.
Drug: Fulvestrant
Select cohorts, as described in the Arms section, will receive fulvestrant 500 milligrams (mg) via intramuscular injection on Days 1 and 15 of Cycle 1, then on Day 1 of each subsequent cycle, 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 PO once daily in 28-day cycles.
Experimental: Phase I, Stage 2: GDC-0032 + Letrozole
Select indication-specific cohorts (E, N, P, Q, R, and S) will receive GDC-0032 administered PO 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 PO once daily in 28-day cycles.
Drug: Letrozole
Select cohorts, as described in the Arms section, will receive letrozole 2.5 mg PO once daily in 28-day cycles until disease progression.
Experimental: Phase I, Stage 2: GDC-0032 as Single Agent
Select indication-specific cohorts (A, B, C, D, G, H, T, and X) will receive GDC-0032 administered PO 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 PO once daily in 28-day cycles.
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 administered PO daily in combination with fulvestrant until disease progression.
Drug: Fulvestrant
Select cohorts, as described in the Arms section, will receive fulvestrant 500 milligrams (mg) via intramuscular injection on Days 1 and 15 of Cycle 1, then on Day 1 of each subsequent cycle, 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 PO once daily in 28-day cycles.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Phase I (Cohorts A through D, G, H, T, 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 patients 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 Response Evaluation Criteria version 1.1 (RECIST v1.1)
  • Phase I (Cohort T): Greater than or equal to (>/=) 1 bi-dimensionally measurable lesion on computed tomography (CT) scan
  • Phase I (Cohort X): 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 14 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01296555

Contacts
Contact: Reference Study ID Number: PMT4979g www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

  Show 34 Study Locations
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Genentech, Inc.
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01296555     History of Changes
Other Study ID Numbers: PMT4979g  GO00886 
Study First Received: February 14, 2011
Last Updated: July 1, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hormones
Estradiol
Letrozole
Fulvestrant
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Antineoplastic Agents, Hormonal
Estrogen Receptor Antagonists
Estrogens

ClinicalTrials.gov processed this record on July 28, 2016