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

NCT ID: NCT02684032

Last Updated: 2022-07-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

141 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-06-14

Study Completion Date

2022-01-19

Brief Summary

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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

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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.

Conditions

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Breast Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Letrozole Cohort

Letrozole combination cohort in dose escalation

Group Type EXPERIMENTAL

Gedatolisib

Intervention Type DRUG

Gedatolisib weekly intravenous starting at 180 mg/week in a 4 week cycle.

Palbociclib

Intervention Type DRUG

Palbociclib initiated at 125 mg daily: 3 out of 4 weeks in a 4 week cycle.

Letrozole

Intervention Type DRUG

Letrozole at 2.5 mg daily

Fulvestrant cohort

Fulvestrant combination cohort in dose escalation

Group Type EXPERIMENTAL

Gedatolisib

Intervention Type DRUG

Gedatolisib weekly intravenous starting at 180 mg/week in a 4 week cycle.

Palbociclib

Intervention Type DRUG

Palbociclib initiated at 125 mg daily: 3 out of 4 weeks in a 4 week cycle.

Fulvestrant

Intervention Type DRUG

Fulvestrant administered intramuscularly at 500 mg on Day 1, 15 and 28 and then every 28 days.

ARM A

Gedatolisib + palbociclib + letrozole in dose expansion

Group Type EXPERIMENTAL

Gedatolisib

Intervention Type DRUG

Gedatolisib weekly intravenous starting at 180 mg/week in a 4 week cycle.

Palbociclib

Intervention Type DRUG

Palbociclib initiated at 125 mg daily: 3 out of 4 weeks in a 4 week cycle.

Letrozole

Intervention Type DRUG

Letrozole at 2.5 mg daily

ARM B

Gedatolisib + palbociclib + fulvestrant in dose expansion

Group Type EXPERIMENTAL

Gedatolisib

Intervention Type DRUG

Gedatolisib weekly intravenous starting at 180 mg/week in a 4 week cycle.

Palbociclib

Intervention Type DRUG

Palbociclib initiated at 125 mg daily: 3 out of 4 weeks in a 4 week cycle.

Fulvestrant

Intervention Type DRUG

Fulvestrant administered intramuscularly at 500 mg on Day 1, 15 and 28 and then every 28 days.

ARM C

Gedatolisib + palbociclib + fulvestrant in dose expansion

Group Type EXPERIMENTAL

Gedatolisib

Intervention Type DRUG

Gedatolisib weekly intravenous starting at 180 mg/week in a 4 week cycle.

Palbociclib

Intervention Type DRUG

Palbociclib initiated at 125 mg daily: 3 out of 4 weeks in a 4 week cycle.

Fulvestrant

Intervention Type DRUG

Fulvestrant administered intramuscularly at 500 mg on Day 1, 15 and 28 and then every 28 days.

Arm D

Gedatolisib (3:1) + palbociclib + fulvestrant in dose expansion

Group Type EXPERIMENTAL

Fulvestrant

Intervention Type DRUG

Fulvestrant administered intramuscularly at 500 mg on Day 1, 15 and 28 and then every 28 days.

Interventions

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Gedatolisib

Gedatolisib weekly intravenous starting at 180 mg/week in a 4 week cycle.

Intervention Type DRUG

Palbociclib

Palbociclib initiated at 125 mg daily: 3 out of 4 weeks in a 4 week cycle.

Intervention Type DRUG

Letrozole

Letrozole at 2.5 mg daily

Intervention Type DRUG

Fulvestrant

Fulvestrant administered intramuscularly at 500 mg on Day 1, 15 and 28 and then every 28 days.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Celcuity Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Igor Gorbatchevsky, MD

Role: STUDY_DIRECTOR

Celcuity Inc

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc.

Corona, California, United States

Site Status

Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc.

Fountain Valley, California, United States

Site Status

Keck Hospital of USC - Norris Healthcare Center (HC3)

Los Angeles, California, United States

Site Status

Keck Hospital of USC

Los Angeles, California, United States

Site Status

LAC+USC Medical Center

Los Angeles, California, United States

Site Status

USC/Norris Comprehensive Cancer Center / Investigational Drug Services

Los Angeles, California, United States

Site Status

USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc.

Riverside, California, United States

Site Status

UCSF - Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Site Status

UCSF - Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Site Status

University of Colorado Hospital - Anschutz Inpatient Pavilion (AiP)

Aurora, Colorado, United States

Site Status

University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)

Aurora, Colorado, United States

Site Status

University of Colorado Hospital - Clinical Trials Office (CTO)

Aurora, Colorado, United States

Site Status

University of Colorado Hospital- Anschutz Cancer Pavilion (ACP)

Aurora, Colorado, United States

Site Status

Moffitt Cancer Center Richard M Schulze Family Foundation Outpatient Center at McKinley Campus

Tampa, Florida, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Emory University Hospital Midtown

Atlanta, Georgia, United States

Site Status

Emory University Hospital

Atlanta, Georgia, United States

Site Status

The Emory Clinic

Atlanta, Georgia, United States

Site Status

Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Karmanos Cancer Institute

Farmington Hills, Michigan, United States

Site Status

UNC Cancer Hospital Infusion Pharmacy

Chapel Hill, North Carolina, United States

Site Status

UNC Hospitals, The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

The Ohio State University Wexner Medical Center James Cancer Hospital

Columbus, Ohio, United States

Site Status

Stefanie Spielman Comprehensive Breast Cancer

Columbus, Ohio, United States

Site Status

Thomas Jefferson University - Clinical and Regulatory

Philadelphia, Pennsylvania, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

Vanderbilt Breast Center at One Hundred Oaks

Nashville, Tennessee, United States

Site Status

Henry-Joyce Cancer Clinic

Nashville, Tennessee, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

U.T. MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status

Seattle Cancer Care Alliance (SCCA) Investigational Drug Services

Seattle, Washington, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Layman RM, Han HS, Rugo HS, Stringer-Reasor EM, Specht JM, Dees EC, Kabos P, Suzuki S, Mutka SC, Sullivan BF, Gorbatchevsky I, Wesolowski R. Gedatolisib in combination with palbociclib and endocrine therapy in women with hormone receptor-positive, HER2-negative advanced breast cancer: results from the dose expansion groups of an open-label, phase 1b study. Lancet Oncol. 2024 Apr;25(4):474-487. doi: 10.1016/S1470-2045(24)00034-2.

Reference Type DERIVED
PMID: 38547892 (View on PubMed)

Related Links

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https://pmiform.com/clinical-trial-info-request?StudyID=B2151009

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Other Identifiers

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B2151009

Identifier Type: -

Identifier Source: org_study_id

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