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
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT02684032
- Lead Sponsor
- Celcuity Inc
- Brief Summary
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 141
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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.
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Histologically or cytologically proven diagnosis of breast cancer with evidence of metastasis.
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Documentation of estrogen receptor positive ((ER+), human epidermal growth factor receptor 2 (HER2 negative (HER2-)) tumor.
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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.
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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/Arm D: 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.
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Measurable disease as defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
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Bone only patients during dose escalation portion.
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Availability of archival tumor biopsy sample or willing to provide fresh biopsy if not available.
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Eastern Cooperative Oncology Group [ECOG] performance must be 0 or 1.
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Adequate bone marrow, renal and liver function.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm D Fulvestrant Gedatolisib (3:1) + palbociclib + fulvestrant in dose expansion ARM A Letrozole Gedatolisib + palbociclib + letrozole in dose expansion Fulvestrant cohort Fulvestrant Fulvestrant combination cohort in dose escalation Letrozole Cohort Gedatolisib Letrozole combination cohort in dose escalation Letrozole Cohort Letrozole Letrozole combination cohort in dose escalation Letrozole Cohort Palbociclib Letrozole combination cohort in dose escalation Fulvestrant cohort Palbociclib Fulvestrant combination cohort in dose escalation ARM A Palbociclib Gedatolisib + palbociclib + letrozole in dose expansion ARM B Palbociclib Gedatolisib + palbociclib + fulvestrant in dose expansion ARM C Palbociclib Gedatolisib + palbociclib + fulvestrant in dose expansion ARM B Fulvestrant Gedatolisib + palbociclib + fulvestrant in dose expansion ARM C Fulvestrant Gedatolisib + palbociclib + fulvestrant in dose expansion Fulvestrant cohort Gedatolisib Fulvestrant combination cohort in dose escalation ARM A Gedatolisib Gedatolisib + palbociclib + letrozole in dose expansion ARM B Gedatolisib Gedatolisib + palbociclib + fulvestrant in dose expansion ARM C Gedatolisib Gedatolisib + palbociclib + fulvestrant in dose expansion
- Primary Outcome Measures
Name Time Method Objective response rate observed in patients in the dose expansion portion 16 weeks Number of patients for each response category, objective response rate (number of patients with a partial response (PR)) relative to the number of response evaluable patients)
Number of participants with dose limiting toxicities up to 28 days
- Secondary Outcome Measures
Name Time Method Tumor response observed in patients in the dose escalation portion 16 weeks Duration of response 16 weeks QTc interval (corrected QT interval) Screening up to 6 months The QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle.
Progression free survival 16 weeks Maximum observed plasma concentration Day 1: 0, 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 24, 72 and 168 hours. Cycle 2 Day 1: 0, 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 24, 72 and 168 hours
Trial Locations
- Locations (36)
The Emory Clinic
🇺🇸Atlanta, Georgia, United States
Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Karmanos Cancer Institute
🇺🇸Farmington Hills, Michigan, United States
Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
Emory University Hospital
🇺🇸Atlanta, Georgia, United States
Keck Hospital of USC - Norris Healthcare Center (HC3)
🇺🇸Los Angeles, California, United States
Keck Hospital of USC
🇺🇸Los Angeles, California, United States
Stefanie Spielman Comprehensive Breast Cancer
🇺🇸Columbus, Ohio, United States
Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc.
🇺🇸Riverside, California, United States
LAC+USC Medical Center
🇺🇸Los Angeles, California, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
UNC Hospitals, The University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
USC/Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Thomas Jefferson University - Clinical and Regulatory
🇺🇸Philadelphia, Pennsylvania, United States
UNC Cancer Hospital Infusion Pharmacy
🇺🇸Chapel Hill, North Carolina, United States
UCSF - Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Vanderbilt Breast Center at One Hundred Oaks
🇺🇸Nashville, Tennessee, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Henry-Joyce Cancer Clinic
🇺🇸Nashville, Tennessee, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
U.T. MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Seattle Cancer Care Alliance (SCCA) Investigational Drug Services
🇺🇸Seattle, Washington, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of Colorado Hospital - Anschutz Inpatient Pavilion (AiP)
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital - Clinical Trials Office (CTO)
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital- Anschutz Cancer Pavilion (ACP)
🇺🇸Aurora, Colorado, United States
Moffitt Cancer Center Richard M Schulze Family Foundation Outpatient Center at McKinley Campus
🇺🇸Tampa, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
The Ohio State University Wexner Medical Center James Cancer Hospital
🇺🇸Columbus, Ohio, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
USC/Norris Comprehensive Cancer Center / Investigational Drug Services
🇺🇸Los Angeles, California, United States
Emory University Hospital Midtown
🇺🇸Atlanta, Georgia, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States