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

Breast Cancer Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT02684032
• Other study ID #: B2151009
• Status: Completed
• Phase: Phase 1
• Start date: June 14, 2016
• Est. completion date: January 19, 2022

Study information

• Verified date: July 2022
• Source: Celcuity, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 141
• Est. completion date: January 19, 2022
• Est. primary completion date: January 19, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Gedatolisib
Gedatolisib weekly intravenous starting at 180 mg/week in a 4 week cycle.
• Palbociclib
Palbociclib initiated at 125 mg daily: 3 out of 4 weeks in a 4 week cycle.
• Letrozole
Letrozole at 2.5 mg daily
• Fulvestrant
Fulvestrant administered intramuscularly at 500 mg on Day 1, 15 and 28 and then every 28 days.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University Hospital	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	The Emory Clinic	Atlanta	Georgia
United States	Winship Cancer Institute	Atlanta	Georgia
United States	University of Colorado Hospital - Anschutz Inpatient Pavilion (AiP)	Aurora	Colorado
United States	University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)	Aurora	Colorado
United States	University of Colorado Hospital - Clinical Trials Office (CTO)	Aurora	Colorado
United States	University of Colorado Hospital- Anschutz Cancer Pavilion (ACP)	Aurora	Colorado
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	UNC Cancer Hospital Infusion Pharmacy	Chapel Hill	North Carolina
United States	UNC Hospitals, The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Stefanie Spielman Comprehensive Breast Cancer	Columbus	Ohio
United States	The Ohio State University Wexner Medical Center James Cancer Hospital	Columbus	Ohio
United States	Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc.	Corona	California
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Karmanos Cancer Institute	Farmington Hills	Michigan
United States	Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc.	Fountain Valley	California
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	U.T. MD Anderson Cancer Center	Houston	Texas
United States	Keck Hospital of USC	Los Angeles	California
United States	Keck Hospital of USC - Norris Healthcare Center (HC3)	Los Angeles	California
United States	LAC+USC Medical Center	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center / Investigational Drug Services	Los Angeles	California
United States	Henry-Joyce Cancer Clinic	Nashville	Tennessee
United States	Vanderbilt Breast Center at One Hundred Oaks	Nashville	Tennessee
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Thomas Jefferson University - Clinical and Regulatory	Philadelphia	Pennsylvania
United States	Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc.	Riverside	California
United States	UCSF - Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	UCSF - Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Seattle Cancer Care Alliance (SCCA) Investigational Drug Services	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Moffitt Cancer Center	Tampa	Florida
United States	Moffitt Cancer Center Richard M Schulze Family Foundation Outpatient Center at McKinley Campus	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Celcuity, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with dose limiting toxicities		up to 28 days
Primary	Objective response rate observed in patients in the dose expansion portion	Number of patients for each response category, objective response rate (number of patients with a complete response (CR)) relative to the number of response evaluable patients	16 weeks
Primary	Objective response rate observed in patients in the dose expansion portion	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)	16 weeks
Secondary	Tumor response observed in patients in the dose escalation portion		16 weeks
Secondary	Duration of response		16 weeks
Secondary	QTc interval (corrected QT interval)	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.	Screening up to 6 months
Secondary	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
Secondary	Progression free survival		16 weeks

External Links

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