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

Sponsor

Celcuity, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02684032

Collaborator

(none)

141

Enrollment

Locations

Arms

67.2

Actual Duration (Months)

3.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Gedatolisib Drug: Palbociclib Drug: Letrozole Drug: Fulvestrant	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

141 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Jun 14, 2016

Actual Primary Completion Date :

Jan 19, 2022

Actual Study Completion Date :

Jan 19, 2022

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

Number of participants with dose limiting toxicities [up to 28 days]
Objective response rate observed in patients in the dose expansion portion [16 weeks]
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
Objective response rate observed in patients in the dose expansion portion [16 weeks]
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)

Secondary Outcome Measures

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]
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.
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	University of Alabama at Birmingham	Birmingham	Alabama	United States	35249
3	Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc.	Corona	California	United States	92879
4	Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc.	Fountain Valley	California	United States	92708
5	Keck Hospital of USC - Norris Healthcare Center (HC3)	Los Angeles	California	United States	90033
6	Keck Hospital of USC	Los Angeles	California	United States	90033
7	LAC+USC Medical Center	Los Angeles	California	United States	90033
8	USC/Norris Comprehensive Cancer Center / Investigational Drug Services	Los Angeles	California	United States	90033
9	USC/Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
10	Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc.	Riverside	California	United States	92501
11	UCSF - Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94115
12	UCSF - Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94158
13	University of Colorado Hospital - Anschutz Inpatient Pavilion (AiP)	Aurora	Colorado	United States	80045
14	University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)	Aurora	Colorado	United States	80045
15	University of Colorado Hospital - Clinical Trials Office (CTO)	Aurora	Colorado	United States	80045
16	University of Colorado Hospital- Anschutz Cancer Pavilion (ACP)	Aurora	Colorado	United States	80045
17	Moffitt Cancer Center Richard M Schulze Family Foundation Outpatient Center at McKinley Campus	Tampa	Florida	United States	33612
18	Moffitt Cancer Center	Tampa	Florida	United States	33612
19	Emory University Hospital Midtown	Atlanta	Georgia	United States	30308
20	Emory University Hospital	Atlanta	Georgia	United States	30322
21	The Emory Clinic	Atlanta	Georgia	United States	30322
22	Winship Cancer Institute	Atlanta	Georgia	United States	30322
23	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
24	University of Michigan	Ann Arbor	Michigan	United States	48109
25	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
26	Karmanos Cancer Institute	Farmington Hills	Michigan	United States	48334
27	UNC Cancer Hospital Infusion Pharmacy	Chapel Hill	North Carolina	United States	27514
28	UNC Hospitals, The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27514
29	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
30	The Ohio State University Wexner Medical Center James Cancer Hospital	Columbus	Ohio	United States	43210
31	Stefanie Spielman Comprehensive Breast Cancer	Columbus	Ohio	United States	43212
32	Thomas Jefferson University - Clinical and Regulatory	Philadelphia	Pennsylvania	United States	19107
33	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
34	Vanderbilt Breast Center at One Hundred Oaks	Nashville	Tennessee	United States	37204
35	Henry-Joyce Cancer Clinic	Nashville	Tennessee	United States	37232
36	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
37	U.T. MD Anderson Cancer Center	Houston	Texas	United States	77030
38	Virginia Cancer Specialists, PC	Fairfax	Virginia	United States	22031
39	Seattle Cancer Care Alliance (SCCA) Investigational Drug Services	Seattle	Washington	United States	98109
40	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
41	University of Washington Medical Center	Seattle	Washington	United States	98195