Clinical Trials /

Clinical Trial to Evaluate the Safety and Effectiveness of GDC-0032 When Given Alongside Tamoxifen

NCT02285179

Description:

This study is designed as a phase 1 dose escalation study followed by a randomised phase II study. The study will be performed in three different centres: Addenbrooke & Cambridge university (Cambridge, UK), Netherlands Cancer Institute Amsterdam), and Vall d'Hebron Hospital (Barcelona, Spain). Three to six patients will be followed for one completed cycle of therapy (28 days) and subsequent enrolment of new cohorts will be based on the safety assessment in that first cycle and the documentation of dose limiting toxicities. To determine the safety and efficacy of tamoxifen in combination with the isoform selective Pi3K inhibitor GDC-0032 compared with tamoxifen alone.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Clinical Trial to Evaluate the Safety and Effectiveness of <span class="go-doc-concept go-doc-intervention">GDC-0032</span> When Given Alongside <span class="go-doc-concept go-doc-intervention">Tamoxifen</span>

Title

  • Brief Title: Clinical Trial to Evaluate the Safety and Effectiveness of GDC-0032 When Given Alongside Tamoxifen
  • Official Title: Phase I/Prospective Randomized Phase II Trial Of the Safety and Efficacy of Tamoxifen in Combination With GDC-0032 Compared With Tamoxifen alONe.
  • Clinical Trial IDs

    NCT ID: NCT02285179

    ORG ID: M14POS

    Trial Conditions

    Breast Cancer

    Ovarian Cancer

    Cancer of the Uterus

    Trial Interventions

    Drug Synonyms Arms
    GDC-0032 tamoxifen and GDC-0032
    Tamoxifen tamoxifen and GDC-0032

    Trial Purpose

    This study is designed as a phase 1 dose escalation study followed by a randomised phase II
    study. The study will be performed in three different centres: Addenbrooke & Cambridge
    university (Cambridge, UK), Netherlands Cancer Institute Amsterdam), and Vall d'Hebron
    Hospital (Barcelona, Spain).

    Three to six patients will be followed for one completed cycle of therapy (28 days) and
    subsequent enrolment of new cohorts will be based on the safety assessment in that first
    cycle and the documentation of dose limiting toxicities. To determine the safety and
    efficacy of tamoxifen in combination with the isoform selective Pi3K inhibitor GDC-0032
    compared with tamoxifen alone.

    Detailed Description

    To determine the recommended phase II dose (RPTD) of GDC-0032 in combination with tamoxifen
    in hormone receptor positive, HER2 negative metastatic breast cancer patients who have
    progressed after prior endocrine treatment .Description of toxicity profile, severity and
    frequency of adverse events (observed with the combination of GDC-0032 and tamoxifen To
    evaluate the safety and tolerability of GDC-0032 in combination with tamoxifen, recording
    adverse events using CTCAE v. 4.0 criteria To describe the pharmacokinetics of GDC-0032 in
    combination with tamoxifen To investigate the possibility of major drug-drug interactions
    (PK) To obtain proof of target inhibition by selected pharmacodynamic measurements To look
    for preliminary evidence of anti-tumour activity To assess the status of potential
    biomarkers for drug response like PIK3CA gene mutations, relevant proteins and
    phospho-proteins in the PI3K pathway, circulating tumour DNA (ct-DNA) To assess germline DNA
    sequence for pharmacogenetics studies

    Trial Arms

    Name Type Description Interventions
    tamoxifen and GDC-0032 Experimental 20 mg tamoxifen QD and dose escalation GDC-0032 GDC-0032, Tamoxifen

    Eligibility Criteria

    Inclusion criteria:

    - Minimum age for inclusion 18 years and a WHO performance status 2

    - Patients with metastatic or incurable locally advanced disease

    - Female patients with Breast cancer patients with ER and/or PR positive tumours In the
    phase 1b part of the study, breast cancer patients may have either HER2 negative or
    HER2 positive disease.

    - Patients with other cancer types are eligible if the investigator considers that they
    might benefit from endocrine therapy combined with PI3K inhibition

    - During the dose escalation phase 1b, patients may have either measurable or
    non-measurable disease by RECIST criteria

    - Archival tumour tissue is allowed, however fresh biopsies are desirable whenever
    feasible and accessible according to the investigator's judgment

    - Life expectancy 12 weeks.

    - adequate organ and marrow function

    - understanding and complying with the protocol requirements and has signed the
    informed consent document.

    - child bearing potential must have a negative serum or urine pregnancy test within 14
    days prior to registration/randomisation, and must use an effective method of
    contraception during treatment and for at least 60 days after the final dose of study
    drug.

    exclusion criteria:

    - The following restrictions on prior anticancer therapy apply;

    - Endocrine therapies or small molecule targeted (non-cytotoxic) inhibitors within 2
    weeks or 5 half-lives of the compound or active metabolites, whichever is longer,
    before the first dose of the study treatment are not allowed

    --No more than 5 prior chemotherapeutic regimens for metastatic breast cancer

    - Radiation therapy within 2 weeks before the first dose of study treatment, unless of
    palliative intent, not compromising bone marrow function

    - Cytotoxic chemotherapy within 3 weeks, or nitrosoureas or mitomycin C within 6 weeks
    before the first dose of the study treatment

    - Antibody therapy within 4 weeks before the first dose of the study treatment

    - Major surgery or not recovered from major surgery, within 4 weeks before the first
    dose of study treatment

    - Other malignancy with the exclusion of carcinoma in situ.

    - The patient has not recovered from toxicity due to prior therapy to grade 1 or to
    pre-therapy baseline. Patients with grade 2 peripheral neuropathy or grade 2 alopecia
    related to prior therapies are eligible

    - The patient has untreated, symptomatic, or progressive brain metastases. -The patient
    has a history of thrombo-embolic disease or is currently receiving anticoagulation
    with therapeutic doses of warfarin.

    - The patient has prothrombin time/ International Normalized Ratio (PT/ INR) or partial
    thromboplastin time (PTT) test results at screening that are above 1.3 x the
    laboratory upper limit of normal.

    - Patients with a history of Crohn's disease or ulcerative colitis or other forms of
    autoimmune colitis

    - The patient has uncontrolled significant intercurrent illness

    - History of clinically significant cardiac or pulmonary dysfunction-The patient has a
    type 1 or 2 diabetes requiring daily antihyperglycemic medication

    - Corticosteroid use equivalent to more than 10mg prednisone daily

    - The patient is known to be positive for the human immunodeficiency virus (HIV).

    - The patient has a previously identified allergy or hypersensitivity to components of
    the study treatment formulation(s).

    - The patients is unable or unwilling to abide by the study protocol or cooperate fully
    with the investigator or designee

    - Pregnant or nursing women

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Number of patients with MTD toxicity

    Secondary Outcome Measures

    Safety Number of patients with adverse events

    Pharmacokinetics Number of patients with germline DNA sequence

    Response Number of patients with a response to protocol treatment

    Trial Keywords

    GDC-0032

    Pi3K inhibitor

    tamoxifen

    hormone receptor positive

    dose escalation

    RECIST

    pharmacodynamic