Clinical Trials /

A Study To Assess The Tolerability And Clinical Activity Of Gedatolisib In Combination With Palbociclib/Letrozole Or Palbociclib/Fulvestrant In Women With Metastatic Breast Cancer

NCT02684032

Description:

This is a multicenter, open label, Phase 1b study in patients with mBC. This study will have a dose escalation to identify the maximum tolerated dose (MTD) of the combination of gedatolisib plus palbociclib/fulvestrant and gedatolisib plus palbociclib/letrozole and expansion to estimate the objective response rate (OR) of the combination of gedatolisib plus palbociclib/letrozole or palbociclib/fulvestrant.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

A Study To Assess The Tolerability And Clinical Activity Of <span class="go-doc-concept go-doc-intervention">Gedatolisib</span> In Combination With <span class="go-doc-concept go-doc-intervention">Palbociclib</span>/<span class="go-doc-concept go-doc-intervention">Letrozole</span> Or <span class="go-doc-concept go-doc-intervention">Palbociclib</span>/<span class="go-doc-concept go-doc-intervention">Fulvestrant</span> In Women With <span class="go-doc-concept go-doc-disease">Metastatic Breast Cancer</span>

Title

  • Brief Title: A Study To Assess The Tolerability And Clinical Activity Of Gedatolisib In Combination With Palbociclib/Letrozole Or Palbociclib/Fulvestrant In Women With Metastatic Breast Cancer
  • Official Title: Phase 1b Study To Assess The Safety, Tolerability, And Clinical Activity Of Gedatolisib In Combination With Palbociclib And Either Letrozole Or Fulvestrant In Women With Metastatic Or Locally Advanced/Recurrent Breast Cancer (MBC)
  • Clinical Trial IDs

    NCT ID: NCT02684032

    ORG ID: B2151009

    Trial Conditions

    Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Gedatolisib Letrozole Cohort, Fulvestrant cohort, ARM A, ARM B, ARM C
    Palbociclib Letrozole Cohort, Fulvestrant cohort, ARM A, ARM B, ARM C
    Letrozole Letrozole Cohort, ARM A
    Fulvestrant Fulvestrant cohort, ARM B, ARM C

    Trial Purpose

    This is a multicenter, open label, Phase 1b study in patients with mBC. This study will have
    a dose escalation to identify the maximum tolerated dose (MTD) of the combination of
    gedatolisib plus palbociclib/fulvestrant and gedatolisib plus palbociclib/letrozole and
    expansion to estimate the objective response rate (OR) of the combination of gedatolisib
    plus palbociclib/letrozole or palbociclib/fulvestrant.

    Detailed Description

    This is a multicenter, open label, continuous Phase 1b study in patients with MBC. This
    study will have a dose escalation and expansion. The dose escalation will identify the
    maximum tolerated dose (MTD) of the combination of gedatolisib plus palbociclib/fulvestrant
    and gedatolisib plus palbociclib/letrozole. The expansion will estimate the objective
    response rate (OR) of the combination of gedatolisib plus palbociclib/letrozole and the
    combination of gedatolisib plus palbociclib/fulvestrant.

    Trial Arms

    Name Type Description Interventions
    Letrozole Cohort Experimental Letrozole combination cohort in dose escalation Gedatolisib, Palbociclib, Letrozole
    Fulvestrant cohort Experimental Fulvestrant combination cohort in dose escalation Gedatolisib, Palbociclib, Fulvestrant
    ARM A Experimental Gedatolisib + palbociclib + letrozole in dose expansion Gedatolisib, Palbociclib, Letrozole
    ARM B Experimental Gedatolisib + palbociclib + fulvestrant in dose expansion Gedatolisib, Palbociclib, Fulvestrant
    ARM C Experimental Gedatolisib + palbociclib + fulvestrant in dose expansion Gedatolisib, Palbociclib, Fulvestrant

    Eligibility Criteria

    Inclusion Criteria:

    - Women 18 years of age or older, who are either: Postmenopausal or Pre/perimenopausal
    women with medically-induced menopause by treatment with agents to induce chemical
    menopause.

    - Histologically or cytologically proven diagnosis of breast cancer with evidence of
    metastasis.

    - Documentation of estrogen receptor positive ((ER+), human epidermal growth factor
    receptor 2 (HER2 negative (HER2-)) tumor.

    - Dose Escalation Portion: Patients must satisfy one of the following criteria:

    - Letrozole combination cohort (L): metastatic breast cancer (MBC) with
    progression who are candidates for a letrozole-containing regimen, with
    palbociclib.

    - Fulvestrant combination cohort (F): MBC with progression who are candidates for
    a fulvestrant containing regimen, with palbociclib.

    - Dose Expansion Portion: Patients must satisfy one of the following criteria:

    - Arm A: MBC with progression and no prior endocrine based systemic therapy in the
    metastatic setting;

    - Arm B: MBC with progression during or following one prior endocrine based
    systemic therapy in the metastatic setting, with no prior therapy with any
    cyclin-dependent kinase (CDK) inhibitor;

    - Arm C: MBC with progression during or following one or two prior endocrine based
    systemic therapies in the metastatic setting, and following prior therapy with a
    CDK inhibitor.

    - Measurable disease as defined by Response Evaluation Criteria In Solid Tumors
    (RECIST) version 1.1.

    - Bone only patients during dose escalation portion.

    - Availability of archival tumor biopsy sample or willing to provide fresh biopsy if
    not available.

    - Eastern Cooperative Oncology Group [ECOG] performance must be 0 or 1.

    - Adequate bone marrow, renal and liver function.

    Exclusion Criteria:

    - Prior treatment with a mechanistic target of rapamycin (mTOR) inhibitor or
    phosphoinositide 3-kinase (PI3K) inhibitor.

    - More than 1 line of prior chemotherapy in the treatment of metastatic or locally
    advanced/recurrent disease.

    - Bone only patients during expansion/efficacy portion.

    - Patients with advanced/metastatic disease who have symptomatic visceral spread, and
    who have life threatening complications needing immediate therapy, such as massive
    uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis,
    and over 50% liver replacement with tumor.

    - Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases.

    - Active bacterial, fungal or viral infection.

    - Uncontrolled or significant cardiovascular disease.

    - Radiation therapy within 4 weeks of investigational product.

    - Cytotoxic chemotherapy within 4 weeks of investigational product (6 weeks for
    mitomycin C or nitrosoureas) if immediate prior regimen was administered on an every
    3 4 week schedule or 2 weeks of investigational product if immediate prior regimen
    consisted of weekly therapy.

    - Any other anti cancer agents (eg, hormonal, biological, investigational) within 5
    times the half life prior to investigational product.

    - Impairment of gastro intestinal (GI) function or GI disease.

    - Pregnant female patients; breastfeeding female patients; and female patients of
    childbearing potential who are unwilling or unable to use 2 highly effective methods
    of contraception as outlined in this protocol for the duration of the study and for
    90 days.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Number of participants with dose limiting toxicities

    Objective response rate observed in patients in the dose expansion portion

    Objective response rate observed in patients in the dose expansion portion

    Secondary Outcome Measures

    Tumor response observed in patients in the dose escalation portion

    Duration of response

    QTc interval (corrected QT interval)

    Maximum observed plasma concentration

    Progression free survival

    Trial Keywords

    PI3K (phosphoinositide 3-kinase)

    mTOR (mechanistic target of rapamycin)

    PI3K/mTOR

    metastatic breast cancer (MBC)

    ER+ (estrogen receptor positive)

    HER2- (human epidermal growth factor receptor 2 negative)