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

• ClinicalTrials.gov Identifier: NCT02684032
• Recruitment Status: Completed
• First Posted: February 17, 2016
• Last Update Posted: July 27, 2022
• Sponsor: Celcuity Inc
• Information provided by (Responsible Party): Celcuity Inc

Tracking Information

• First Submitted Date: February 10, 2016
• First Posted Date: February 17, 2016
• Last Update Posted Date: July 27, 2022
• Actual Study Start Date: June 14, 2016
• Actual Primary Completion Date: January 19, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 11, 2016)

• Number of participants with dose limiting toxicities [ Time Frame: up to 28 days ]
• Objective response rate observed in patients in the dose expansion portion [ Time Frame: 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 [ Time Frame: 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)

Original Primary Outcome Measures (submitted: February 11, 2016)

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

Current Secondary Outcome Measures (submitted: February 11, 2016)

• Tumor response observed in patients in the dose escalation portion [ Time Frame: 16 weeks ]
• Duration of response [ Time Frame: 16 weeks ]
• QTc interval (corrected QT interval) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 16 weeks ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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)
• 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.
• 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
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

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

Study Arms

• Experimental: Letrozole Cohort
  Letrozole combination cohort in dose escalation
  Interventions:

  • Drug: Gedatolisib
  • Drug: Palbociclib
  • Drug: Letrozole
• Experimental: Fulvestrant cohort
  Fulvestrant combination cohort in dose escalation
  Interventions:

  • Drug: Gedatolisib
  • Drug: Palbociclib
  • Drug: Fulvestrant
• Experimental: ARM A
  Gedatolisib + palbociclib + letrozole in dose expansion
  Interventions:

  • Drug: Gedatolisib
  • Drug: Palbociclib
  • Drug: Letrozole
• Experimental: ARM B
  Gedatolisib + palbociclib + fulvestrant in dose expansion
  Interventions:

  • Drug: Gedatolisib
  • Drug: Palbociclib
  • Drug: Fulvestrant
• Experimental: ARM C
  Gedatolisib + palbociclib + fulvestrant in dose expansion
  Interventions:

  • Drug: Gedatolisib
  • Drug: Palbociclib
  • Drug: Fulvestrant
• Experimental: Arm D
  Gedatolisib (3:1) + palbociclib + fulvestrant in dose expansion
  Intervention: Drug: Fulvestrant

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 21, 2020): 141
• Original Estimated Enrollment (submitted: February 11, 2016): 121
• Actual Study Completion Date: January 19, 2022
• Actual Primary Completion Date: January 19, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02684032
• Other Study ID Numbers: B2151009
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No
• 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.

• Current Responsible Party: Celcuity Inc
• Original Responsible Party: Pfizer
• Current Study Sponsor: Celcuity Inc
• Original Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Igor Gorbatchevsky, MD; Celcuity Inc

• PRS Account: Celcuity Inc
• Verification Date: July 2022