Clinical trial NCT02684032: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
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)
Lead sponsor: Celcuity Inc
Sponsor class: INDUSTRY
First posted: 2016-02-17
Enrollment: 141
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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/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.
* 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.

Primary outcomes:
measure: Number of participants with dose limiting toxicities
timeFrame: up to 28 days
measure: Objective response rate observed in patients in the dose expansion portion
timeFrame: 16 weeks
measure: Objective response rate observed in patients in the dose expansion portion
timeFrame: 16 weeks
Secondary outcomes:
measure: Tumor response observed in patients in the dose escalation portion
timeFrame: 16 weeks
measure: Duration of response
timeFrame: 16 weeks
measure: QTc interval (corrected QT interval)
timeFrame: Screening up to 6 months
measure: Maximum observed plasma concentration
timeFrame: 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
measure: Progression free survival
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Corona
country: United States
facility: Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc.
state: California
city: Fountain Valley
country: United States
facility: Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc.
state: California
city: Los Angeles
country: United States
facility: Keck Hospital of USC - Norris Healthcare Center (HC3)
state: California
city: Los Angeles
country: United States
facility: Keck Hospital of USC
state: California
city: Los Angeles
country: United States
facility: LAC+USC Medical Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center / Investigational Drug Services
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Riverside
country: United States
facility: Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc.
state: California
city: San Francisco
country: United States
facility: UCSF - Helen Diller Family Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF - Helen Diller Family Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Inpatient Pavilion (AiP)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital - Clinical Trials Office (CTO)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital- Anschutz Cancer Pavilion (ACP)
state: Colorado
city: Tampa
country: United States
facility: Moffitt Cancer Center Richard M Schulze Family Foundation Outpatient Center at McKinley Campus
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: The Emory Clinic
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Farmington Hills
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Chapel Hill
country: United States
facility: UNC Cancer Hospital Infusion Pharmacy
state: North Carolina
city: Chapel Hill
country: United States
facility: UNC Hospitals, The University of North Carolina at Chapel Hill
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center James Cancer Hospital
state: Ohio
city: Columbus
country: United States
facility: Stefanie Spielman Comprehensive Breast Cancer
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University - Clinical and Regulatory
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Breast Center at One Hundred Oaks
state: Tennessee
city: Nashville
country: United States
facility: Henry-Joyce Cancer Clinic
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: U.T. MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance (SCCA) Investigational Drug Services
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: Celcuity Inc
name: Igor Gorbatchevsky, MD
role: STUDY_DIRECTOR
References: