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
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
- Breast Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Female
- Accepts Healthy 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.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
Arm | Description | Assigned Intervention |
---|---|---|
Experimental Letrozole Cohort |
Letrozole combination cohort in dose escalation |
|
Experimental Fulvestrant cohort |
Fulvestrant combination cohort in dose escalation |
|
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 |
|
More Details
- Status
- Completed
- Sponsor
- Celcuity Inc
Study Contact
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.