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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

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

Trial Eligibility

Document

A Dose Escalation Study Evaluating the Safety and Tolerability of <span class="go-doc-concept go-doc-intervention">GDC-0032</span> in Participants With Locally Advanced or Metastatic Solid Tumors or Non-Hodgkin's <span class="go-doc-concept go-doc-disease">Lymphoma</span> (NHL) and in Combination With <span class="go-doc-concept go-doc-intervention">Endocrine Therapy</span> in Locally Advanced or Metastatic Hormone Receptor-Positive <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

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

    NCT ID: NCT01296555

    ORG ID: PMT4979g

    NCI ID: GO00886

    Trial Conditions

    Non-Hodgkin's Lymphoma, Solid Cancers

    Trial Interventions

    Drug Synonyms Arms
    Fulvestrant Phase I, Stage 2: GDC-0032 + Fulvestrant, Phase II: GDC-0032 + Fulvestrant
    GDC-0032 Phase I, Stage 1: GDC-0032 as Single Agent, Phase I, Stage 2: GDC-0032 + Fulvestrant, Phase I, Stage 2: GDC-0032 + Letrozole, Phase I, Stage 2: GDC-0032 as Single Agent, Phase II: GDC-0032 + Fulvestrant
    Letrozole Phase I, Stage 2: GDC-0032 + Letrozole

    Trial 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.

    Detailed Description

    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 PO 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 Select indication-specific cohorts (F, J, K, L, and M) will receive GDC-0032 administered PO in combination with fulvestrant until disease progression. Fulvestrant, GDC-0032
    Phase I, Stage 2: GDC-0032 + Letrozole Experimental Select indication-specific cohorts (E, N, P, Q, R, and S) will receive GDC-0032 administered PO in combination with letrozole until disease progression. GDC-0032, Letrozole
    Phase I, Stage 2: GDC-0032 as Single Agent Experimental Select indication-specific cohorts (A, B, C, D, G, H, T, and X) will receive GDC-0032 administered PO until disease progression. GDC-0032
    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 administered PO daily in combination with fulvestrant until disease progression. Fulvestrant, GDC-0032

    Eligibility 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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Area under the concentration-time curve (AUC) of GDC-0032

    Minimum observed concentration (Cmin) of GDC-0032

    Maximum observed concentration (Cmax) of GDC-0032

    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

    Incidence of dose-limiting toxicities (DLTs) by NCI CTCAE v4.0 grade and associated dose of GDC-0032

    Incidence of Grade 3 and 4 abnormalities in safety-related laboratory parameters and associated dose of GDC-0032

    Phase II: Clinical benefit rate with the combination GDC-0032 + fulvestrant

    Phase II: Objective response rate with the combination GDC-0032 + fulvestrant

    Secondary Outcome Measures

    Phase I: Best overall response

    Phase I: Duration of objective response

    Phase I: Progression-free survival (PFS)

    Phase II: Duration of response with the combination GDC-0032 + fulvestrant

    Phase II: PFS with the combination GDC-0032 + fulvestrant

    Phase II: Overall survival with the combination GDC-0032 + fulvestrant

    Trial Keywords