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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

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ClinicalTrials.gov Identifier: NCT02684032
Recruitment Status : Recruiting
First Posted : February 17, 2016
Last Update Posted : January 17, 2018
Sponsor:
Information provided by (Responsible Party):

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  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Non-Randomized
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 : June 14, 2016
Estimated Primary Completion Date : November 24, 2019
Estimated Study Completion Date : November 24, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
U.S. FDA Resources

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.


Outcome Measures

Primary Outcome Measures :
  1. Number of participants with dose limiting toxicities [ Time Frame: up to 28 days ]
  2. 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

  3. 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)


Secondary Outcome Measures :
  1. Tumor response observed in patients in the dose escalation portion [ Time Frame: 16 weeks ]
  2. Duration of response [ Time Frame: 16 weeks ]
  3. 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.

  4. 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 ]
  5. Progression free survival [ Time Frame: 16 weeks ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
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: 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02684032


Contacts
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35233
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35249
United States, California
Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc. Recruiting
Corona, California, United States, 92879
Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc. Recruiting
Fountain Valley, California, United States, 92708
Keck Hospital of USC Recruiting
Los Angeles, California, United States, 90033
LAC+USC Medical Center Recruiting
Los Angeles, California, United States, 90033
USC/Norris Comprehensive Cancer Center / Investigational Drug Services Recruiting
Los Angeles, California, United States, 90033
USC/Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc. Recruiting
Riverside, California, United States, 92501
UCSF - Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94115
UCSF Medical Center Recruiting
San Francisco, California, United States, 94115
United States, Colorado
DRUG SHIPMENT: ATTN: Research Pharmacist Recruiting
Aurora, Colorado, United States, 80045
University of Colorado Hospital - Anschutz Inpatient Pavillion (AIP) Recruiting
Aurora, Colorado, United States, 80045
University of Colorado Hospital - Anschutz Outpatient Pavilllion (AOP) Recruiting
Aurora, Colorado, United States, 80045
University of Colorado Hospital - Clinical Trials Office (CTO) Recruiting
Aurora, Colorado, United States, 80045
University of Colorado Hospital- Anschutz Caner Pavilion (ACP) Recruiting
Aurora, Colorado, United States, 80045
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute Recruiting
Tampa, Florida, United States, 33612
Moffitt McKinley Outpatient Center Recruiting
Tampa, Florida, United States, 33612
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
United States, Michigan
Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Karmanos Cancer Insutitute - Investigation Pharmacy Recruiting
Detroit, Michigan, United States, 48201
Karmanos Cancer Institute Recruiting
Farmington Hills, Michigan, United States, 48334
United States, North Carolina
UNC Healthcare, NC Cancer Hospital Recruiting
Chapel Hill, North Carolina, United States, 27514
UNC Hospitals, The University of North Carolina at Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599-7600
United States, Ohio
Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
The Ohio State University Wexner Medical Center James Cancer Hospital Recruiting
Columbus, Ohio, United States, 43210
Stephanie Spielman Comprehensive Breast Cancer Recruiting
Columbus, Ohio, United States, 43212
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
U.T. MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02684032     History of Changes
Other Study ID Numbers: B2151009
First Posted: February 17, 2016    Key Record Dates
Last Update Posted: January 17, 2018
Last Verified: January 2018

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
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Fulvestrant
Palbociclib
Estradiol
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Estrogen Receptor Antagonists
Estrogens
Hormones
Protein Kinase Inhibitors