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

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)

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Gedatolisib; Drug: Palbociclib; Drug: Letrozole; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 141
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham
  • California
    • Corona, California, United States, 92879
      • Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc.
    • Fountain Valley, California, United States, 92708
      • Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc.
    • Los Angeles, California, United States, 90033
      • USC/Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • Keck Hospital of USC
    • Los Angeles, California, United States, 90033
      • USC/Norris Comprehensive Cancer Center / Investigational Drug Services
    • Los Angeles, California, United States, 90033
      • LAC+USC Medical Center
    • Los Angeles, California, United States, 90033
      • Keck Hospital of USC - Norris Healthcare Center (HC3)
    • Riverside, California, United States, 92501
      • Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc.
    • San Francisco, California, United States, 94115
      • UCSF - Helen Diller Family Comprehensive Cancer Center
    • San Francisco, California, United States, 94158
      • UCSF - Helen Diller Family Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital - Clinical Trials Office (CTO)
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital- Anschutz Cancer Pavilion (ACP)
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center Richard M Schulze Family Foundation Outpatient Center at McKinley Campus
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown
    • Atlanta, Georgia, United States, 30322
      • The Emory Clinic
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
    • Farmington Hills, Michigan, United States, 48334
      • Karmanos Cancer Institute
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • UNC Cancer Hospital Infusion Pharmacy
    • Chapel Hill, North Carolina, United States, 27514
      • UNC Hospitals, The University of North Carolina at Chapel Hill
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
    • Columbus, Ohio, United States, 43212
      • Stefanie Spielman Comprehensive Breast Cancer
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center James Cancer Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University - Clinical and Regulatory
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Henry-Joyce Cancer Clinic
    • Nashville, Tennessee, United States, 37204
      • Vanderbilt Breast Center at One Hundred Oaks
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Md Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • U.T. MD Anderson Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists, PC
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance (SCCA) Investigational Drug Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Letrozole Cohort; Letrozole combination cohort in dose escalation	Drug: Gedatolisib; Gedatolisib weekly intravenous starting at 180 mg/week in a 4 week cycle.; Drug: Palbociclib; Palbociclib initiated at 125 mg daily: 3 out of 4 weeks in a 4 week cycle.; Drug: Letrozole; Letrozole at 2.5 mg daily
EXPERIMENTAL: Fulvestrant cohort; Fulvestrant combination cohort in dose escalation	Drug: Gedatolisib; Gedatolisib weekly intravenous starting at 180 mg/week in a 4 week cycle.; Drug: Palbociclib; Palbociclib initiated at 125 mg daily: 3 out of 4 weeks in a 4 week cycle.; Drug: Fulvestrant; Fulvestrant administered intramuscularly at 500 mg on Day 1, 15 and 28 and then every 28 days.
EXPERIMENTAL: ARM A; Gedatolisib + palbociclib + letrozole in dose expansion	Drug: Gedatolisib; Gedatolisib weekly intravenous starting at 180 mg/week in a 4 week cycle.; Drug: Palbociclib; Palbociclib initiated at 125 mg daily: 3 out of 4 weeks in a 4 week cycle.; Drug: Letrozole; Letrozole at 2.5 mg daily
EXPERIMENTAL: ARM B; Gedatolisib + palbociclib + fulvestrant in dose expansion	Drug: Gedatolisib; Gedatolisib weekly intravenous starting at 180 mg/week in a 4 week cycle.; Drug: Palbociclib; Palbociclib initiated at 125 mg daily: 3 out of 4 weeks in a 4 week cycle.; Drug: Fulvestrant; Fulvestrant administered intramuscularly at 500 mg on Day 1, 15 and 28 and then every 28 days.
EXPERIMENTAL: ARM C; Gedatolisib + palbociclib + fulvestrant in dose expansion	Drug: Gedatolisib; Gedatolisib weekly intravenous starting at 180 mg/week in a 4 week cycle.; Drug: Palbociclib; Palbociclib initiated at 125 mg daily: 3 out of 4 weeks in a 4 week cycle.; Drug: Fulvestrant; Fulvestrant administered intramuscularly at 500 mg on Day 1, 15 and 28 and then every 28 days.
EXPERIMENTAL: Arm D; Gedatolisib (3:1) + palbociclib + fulvestrant in dose expansion	Drug: Fulvestrant; Fulvestrant administered intramuscularly at 500 mg on Day 1, 15 and 28 and then every 28 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with dose limiting toxicities		up to 28 days
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor response observed in patients in the dose escalation portion		16 weeks
Duration of response		16 weeks
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
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
Progression free survival		16 weeks

Collaborators and Investigators

• Sponsor: Celcuity, Inc.
• Investigators: Study Director: Igor Gorbatchevsky, MD, Celcuity, Inc.

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 14, 2016
• Primary Completion (ACTUAL): January 19, 2022
• Study Completion (ACTUAL): January 19, 2022

Study Registration Dates

• First Submitted: February 10, 2016
• First Submitted That Met QC Criteria: February 11, 2016
• First Posted (ESTIMATE): February 17, 2016

Study Record Updates

• Last Update Posted (ACTUAL): July 27, 2022
• Last Update Submitted That Met QC Criteria: July 25, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: metastatic breast cancer (MBC); PI3K/mTOR; PI3K (phosphoinositide 3-kinase); mTOR (mechanistic target of rapamycin); ER+ (estrogen receptor positive); HER2- (human epidermal growth factor receptor 2 negative)
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protein Kinase Inhibitors; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Estrogen Receptor Antagonists; Letrozole; Fulvestrant; Palbociclib; Gedatolisib
• Other Study ID Numbers: B2151009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Celcuity will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions.