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 |
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Recruitment Status :
Completed
First Posted : February 17, 2016
Last Update Posted : July 27, 2022
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Sponsor:
Celcuity Inc
Information provided by (Responsible Party):
Celcuity Inc
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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 |
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 (Clinical Trial) |
| 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 : | June 14, 2016 |
| Actual Primary Completion Date : | January 19, 2022 |
| Actual Study Completion Date : | January 19, 2022 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Breast cancer
MedlinePlus related topics:
Breast Cancer
| Arm | Intervention/treatment |
|---|---|
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Experimental: Letrozole Cohort
Letrozole combination cohort in dose escalation
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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 |
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Experimental: Fulvestrant cohort
Fulvestrant combination cohort in dose escalation
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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. |
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Experimental: ARM A
Gedatolisib + palbociclib + letrozole in dose expansion
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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 |
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Experimental: ARM B
Gedatolisib + palbociclib + fulvestrant in dose expansion
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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. |
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Experimental: ARM C
Gedatolisib + palbociclib + fulvestrant in dose expansion
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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. |
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Experimental: Arm D
Gedatolisib (3:1) + palbociclib + fulvestrant in dose expansion
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Drug: Fulvestrant
Fulvestrant administered intramuscularly at 500 mg on Day 1, 15 and 28 and then every 28 days. |
Primary Outcome Measures :
- 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)
Secondary Outcome Measures :
- 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 ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| 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.
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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.
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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.
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
Locations
Show 41 study locations
Sponsors and Collaborators
Celcuity Inc
Investigators
| Study Director: | Igor Gorbatchevsky, MD | Celcuity Inc |
Additional Information:
| Responsible Party: | Celcuity Inc |
| ClinicalTrials.gov Identifier: | NCT02684032 |
| Other Study ID Numbers: |
B2151009 |
| First Posted: | February 17, 2016 Key Record Dates |
| Last Update Posted: | July 27, 2022 |
| Last Verified: | July 2022 |
| Individual Participant Data (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. |
Keywords provided by Celcuity Inc:
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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:
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Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Letrozole Fulvestrant Palbociclib Gedatolisib 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 Protein Kinase Inhibitors |