Clinical Trial - NCT02684032

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

Recruiting

Sponsor: Pfizer

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT02684032

Protocol Info

Short Description: 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
Long Description: 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)
MGH Status: Open
Sponsor: Pfizer
Disease Program: Breast

Next Steps


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Purpose

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 Title Intervention Phase
Breast Cancer Gedatolisib Palbociclib Letrozole Fulvestrant Phase 1
Study Type Interventional
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)

Primary Outcome Measures

Number of participants with dose limiting toxicities [Time Frame: up to 28 days] [Designated as safety issue: ]

Objective response rate observed in patients in the dose expansion portion [Time Frame: 16 weeks] [Designated as safety issue: ]

Objective response rate observed in patients in the dose expansion portion [Time Frame: 16 weeks] [Designated as safety issue: ]


Secondary Outcome Measures

Tumor response observed in patients in the dose escalation portion [Time Frame: 16 weeks] [Designated as safety issue: ]

Duration of response [Time Frame: 16 weeks] [Designated as safety issue: ]

QTc interval (corrected QT interval) [Time Frame: Screening up to 6 months] [Designated as safety issue: ]

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] [Designated as safety issue: ]

Progression free survival [Time Frame: 16 weeks] [Designated as safety issue: ]

Estimated Enrollment: 148
Study Start Date: June 2016
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: June 2020
Arms Assigned Interventions

Experimental:Letrozole Cohort

Letrozole combination cohort in dose escalation
Drug:Letrozole
Letrozole at 2.5 mg daily

Experimental:Fulvestrant cohort

Fulvestrant combination cohort in dose escalation
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

Experimental:ARM B

Gedatolisib + palbociclib + fulvestrant in dose expansion

Experimental:ARM C

Gedatolisib + palbociclib + fulvestrant in dose expansion

Experimental:Arm D

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

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: Female

Accepts Healthly Volunteers: No

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT02684032

Locations

  • United States, Alabama
    • University of Alabama at Birmingham Birmingham, Alabama, United States, 35233
    • University of Alabama at Birmingham Birmingham, Alabama, United States, 35249
  • United States, California
    • Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc. Corona, California, United States, 92879
    • Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc. Fountain Valley, California, United States, 92708
    • Keck Hospital of USC Los Angeles, California, United States, 90033
    • LAC+USC Medical Center Los Angeles, California, United States, 90033
    • USC/Norris Comprehensive Cancer Center / Investigational Drug Services Los Angeles, California, United States, 90033
    • USC/Norris Comprehensive Cancer Center Los Angeles, California, United States, 90033
    • Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc. Riverside, California, United States, 92501
    • UCSF - Helen Diller Family Comprehensive Cancer Center San Francisco, California, United States, 94115
    • UCSF Medical Center San Francisco, California, United States, 94115
  • United States, Colorado
    • University of Colorado Hospital - Anschutz Inpatient Pavillion (AIP) Aurora, Colorado, United States, 80045
    • University of Colorado Hospital - Anschutz Outpatient Pavilllion (AOP) Aurora, Colorado, United States, 80045
    • University of Colorado Hospital - Clinical Trials Office (CTO) Aurora, Colorado, United States, 80045
    • University of Colorado Hospital- Anschutz Caner Pavilion (ACP) Aurora, Colorado, United States, 80045
  • United States, Florida
    • H. Lee Moffitt Cancer Center & Research Institute Tampa, Florida, United States, 33612
    • Moffitt McKinley Outpatient Center Tampa, Florida, United States, 33612
  • United States, Georgia
    • Emory University Hospital Midtown Atlanta, Georgia, United States, 30308
    • Emory University Hospital Atlanta, Georgia, United States, 30322
    • The Emory Clinic Atlanta, Georgia, United States, 30322
    • Winship Cancer Institute/Emory University-Investigational Drug Service Atlanta, Georgia, United States, 30322
    • Winship Cancer Institute Atlanta, Georgia, United States, 30322
  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02114
  • United States, Michigan
    • University of Michigan Hospitals Ann Arbor, Michigan, United States, 48109-5008
    • University of Michigan Ann Arbor, Michigan, United States, 48109
    • Karmanos Cancer Institute Detroit, Michigan, United States, 48201
    • Karmanos Cancer Insutitute - Investigation Pharmacy Detroit, Michigan, United States, 48201
    • Karmanos Cancer Institute Farmington Hills, Michigan, United States, 48334
  • United States, North Carolina
    • UNC Cancer Hospital Infusion Pharmacy Chapel Hill, North Carolina, United States, 27514
    • UNC Hospitals, The University of North Carolina at Chapel Hill Chapel Hill, North Carolina, United States, 27599-7600
  • United States, Ohio
    • Ohio State University Comprehensive Cancer Center Columbus, Ohio, United States, 43210
    • The Ohio State University Wexner Medical Center James Cancer Hospital Columbus, Ohio, United States, 43210
    • Stephanie Spielman Comprehensive Breast Cancer Columbus, Ohio, United States, 43212
  • United States, Pennsylvania
    • Thomas Jefferson University - Clinical and Regulatory Philadelphia, Pennsylvania, United States, 19107
    • Thomas Jefferson University Investigational Drug Services Philadelphia, Pennsylvania, United States, 19107
    • Thomas Jefferson University, Investigational Drug Service Philadelphia, Pennsylvania, United States, 19107
    • Thomas Jefferson University Philadelphia, Pennsylvania, United States, 19107
  • United States, Tennessee
    • Vanderbilt Breast Center at One Hundred Oaks Nashville, Tennessee, United States, 37204
    • Vanderbilt Health Pharmacy One Hundred Oaks Nashville, Tennessee, United States, 37204
    • Henry-Joyce Cancer Clinic Nashville, Tennessee, United States, 37232
  • United States, Texas
    • The University of Texas MD Anderson Cancer Center Houston, Texas, United States, 77030
    • U.T. MD Anderson Cancer Center Houston, Texas, United States, 77030
  • United States, Virginia
    • Virginia Cancer Specialists, PC Fairfax, Virginia, United States, 22031
  • United States, Washington
    • Seattle Cancer Care Alliance (SCCA) Investigational Drug Services Seattle, Washington, United States, 98109
    • Seattle Cancer Care Alliance Seattle, Washington, United States, 98109
    • University of Washington Medical Center Seattle, Washington, United States, 98195

Sponsors and Collaborators

Pfizer

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT02684032
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Pfizer:

PI3K (phosphoinositide 3-kinase)

mTOR (mechanistic target of rapamycin)

PI3K/mTOR

metastatic breast cancer (MBC)

ER+ (estrogen receptor positive)

HER2- (human epidermal growth factor receptor 2 negative)

Additional relevant MeSH terms:

Breast Neoplasms

Letrozole

Fulvestrant

Palbociclib

Gedatolisib

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on August 15, 2019