NCT02684032|CompletedPhase 1

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)

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1 other identifier

B2151009

Study Type

interventional

Target

141

Locations

1 country

Sites

Timeline

RegisteredFeb 2016

StartedJun 2016

CompletionJan 2022

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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

141

participants targeted

Target at P75+ for phase_1 breast-cancer

Timeline

Completed

Started Jun 2016

Typical duration for phase_1 breast-cancer

Geographic Reach

1 country

41 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

5.6 years study duration

First Submitted

Initial submission to the registry

February 10, 2016

Completed

7 days until next milestone

First Posted

Study publicly available on registry

February 17, 2016

Completed

4 months until next milestone

Study Start

First participant enrolled

June 14, 2016

Completed

5.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 19, 2022

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 19, 2022

Completed

Last Updated

July 27, 2022

Status Verified

July 1, 2022

Enrollment Period

5.6 years

First QC Date

February 10, 2016

Last Update Submit

July 25, 2022

Conditions

Breast Cancer

Keywords

PI3K (phosphoinositide 3-kinase)mTOR (mechanistic target of rapamycin)PI3K/mTORmetastatic breast cancer (MBC)ER+ (estrogen receptor positive)HER2- (human epidermal growth factor receptor 2 negative)

Outcome Measures

Primary Outcomes (3)

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 Outcomes (5)

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
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

Study Arms (6)

Letrozole Cohort

EXPERIMENTAL

Letrozole combination cohort in dose escalation

Drug: GedatolisibDrug: PalbociclibDrug: Letrozole

Fulvestrant cohort

EXPERIMENTAL

Fulvestrant combination cohort in dose escalation

Drug: GedatolisibDrug: PalbociclibDrug: Fulvestrant

ARM A

EXPERIMENTAL

Gedatolisib + palbociclib + letrozole in dose expansion

Drug: GedatolisibDrug: PalbociclibDrug: Letrozole

ARM B

EXPERIMENTAL

Gedatolisib + palbociclib + fulvestrant in dose expansion

Drug: GedatolisibDrug: PalbociclibDrug: Fulvestrant

ARM C

EXPERIMENTAL

Gedatolisib + palbociclib + fulvestrant in dose expansion

Drug: GedatolisibDrug: PalbociclibDrug: Fulvestrant

Arm D

EXPERIMENTAL

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

Drug: Fulvestrant

Interventions

GedatolisibDRUG

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

ARM AARM BARM CFulvestrant cohortLetrozole Cohort

PalbociclibDRUG

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

ARM AARM BARM CFulvestrant cohortLetrozole Cohort

LetrozoleDRUG

Letrozole at 2.5 mg daily

ARM ALetrozole Cohort

FulvestrantDRUG

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

ARM BARM CArm DFulvestrant cohort

Eligibility Criteria

Age18 Years+

Sexfemale(Gender-based eligibility)

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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.

You may not qualify if:

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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Celcuity Inclead

Study Sites (41)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

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

Corona, California, 92879, United States

Location

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

Fountain Valley, California, 92708, United States

Location

Keck Hospital of USC - Norris Healthcare Center (HC3)