Abexinostat, Palbociclib, and Fulvestrant for the Treatment of Breast or Gynecologic Cancer
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|ClinicalTrials.gov Identifier: NCT04498520|
Recruitment Status : Not yet recruiting
First Posted : August 4, 2020
Last Update Posted : August 4, 2020
|Condition or disease||Intervention/treatment||Phase|
|Anatomic Stage III Breast Cancer AJCC v8 Anatomic Stage IIIA Breast Cancer AJCC v8 Anatomic Stage IIIB Breast Cancer AJCC v8 Anatomic Stage IIIC Breast Cancer AJCC v8 Anatomic Stage IV Breast Cancer AJCC v8 Hormone Receptor Positive Breast Carcinoma Locally Advanced Breast Carcinoma Metastatic Breast Carcinoma Metastatic Endometrioid Adenocarcinoma Metastatic Fallopian Tube Carcinoma Metastatic HER2 Negative Breast Carcinoma Metastatic Malignant Solid Neoplasm Metastatic Ovarian Carcinoma Metastatic Primary Peritoneal Carcinoma Prognostic Stage III Breast Cancer AJCC v8 Prognostic Stage IIIA Breast Cancer AJCC v8 Prognostic Stage IIIB Breast Cancer AJCC v8 Prognostic Stage IIIC Breast Cancer AJCC v8 Prognostic Stage IV Breast Cancer AJCC v8 Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Refractory Breast Carcinoma Stage IV Fallopian Tube Cancer AJCC v8 Stage IV Ovarian Cancer AJCC v8 Stage IV Primary Peritoneal Cancer AJCC v8 Stage IV Uterine Corpus Cancer AJCC v8 Stage IVA Fallopian Tube Cancer AJCC v8 Stage IVA Ovarian Cancer AJCC v8 Stage IVA Primary Peritoneal Cancer AJCC v8 Stage IVA Uterine Corpus Cancer AJCC v8 Stage IVB Fallopian Tube Cancer AJCC v8 Stage IVB Ovarian Cancer AJCC v8 Stage IVB Primary Peritoneal Cancer AJCC v8 Stage IVB Uterine Corpus Cancer AJCC v8||Drug: Abexinostat Tosylate Drug: Fulvestrant Drug: Palbociclib||Phase 1|
- To determine the safety and tolerability of abexinostat tosylate (abexinostat) and palbociclib in combination with fulvestrant.
- To determine the maximum tolerated dose (MTD) for abexinostat and palbociclib when combined with fulvestrant at standard dose.
- To describe the pharmacokinetics associated with abexinostat.
- To describe the efficacy of abexinostat and palbociclib in combination with fulvestrant in patients with antiestrogen refractory estrogen receptor positive (ER+), HER2 negative(-) breast cancer and gynecological metastatic tumors.
- To assess the clinical benefit rate (CBR) defined as complete response (CR), partial response (PR), and stable disease (SD) at 6 months and progression free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.
- To assess correlations between overall response rate (ORR), CBR at 6 months, and progression free survival (PFS) with genomic aberrations assessed as cell free tumor deoxyribonucleic acid (DNA) and histone acetylation on peripheral blood.
- To assess correlations between ORR, CBR at 6 months, and PFS endpoints and peripheral blood mononuclear cell (PBMC) histone deacetylase (HDAC) gene expression, PBMC acetylation in vivo and ex vivo.
OUTLINE: This is a dose-escalation study of abexinostat and palbociclib.
Patients receive abexinostat orally (PO) twice daily (BID) on days 1-4, 8-11, and 15-18, palbociclib PO once daily (QD) on days 1-21, and fulvestrant intramuscularly (IM) on days 1 and 15 of cycle 1 and day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients will be followed for 90 days after completion of treatment or removal from study, or until death, whichever occurs first.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||70 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Trial of Abexinostat Combined With Palbociclib and Fulvestrant in Patients With Antiestrogen Refractory ER+, HER2- Breast Cancer and Gynecological Metastatic Tumors|
|Estimated Study Start Date :||September 1, 2020|
|Estimated Primary Completion Date :||October 31, 2021|
|Estimated Study Completion Date :||January 31, 2022|
Experimental: Treatment (abexinostat tosylate, palbociclib, fulvestrant)
Patients receive abexinostat PO BID on days 1-4, 8-11, and 15-18, palbociclib PO QD on days 1-21, and fulvestrant IM on days 1 and 15 of cycle 1 and day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Abexinostat Tosylate
Other Name: PCI-24781 Tosylate
- Dose limiting toxicities (DLTs) [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]An occurrence of any of the protocol specified toxicities occurring during cycle 1: (1) Hematologic - Grade 4 neutropenia lasting > 5 consecutive days, Grade 3/4 febrile neutropenia, Grade 4 thrombocytopenia lasting >=7 days, or Grade 3 or 4 thrombocytopenia w/ clinically significant bleeding or requirement for platelet transfusion, (2) Non-hematologic: Any adverse event (AE) >= Grade 3, with the exceptions of Grade 3 nausea, vomiting, diarrhea, clinically insignificant laboratory abnormality, or fatigue resolving to Grade <=2 w/in 72 hours (3) Any AE that results in delay in administration of abexinostat or palbociclib of less than 75% and a delay of more than 7 days before starting cycle 2 unless the AE can be clearly attributed to an extraneous cause. DLTs are classified according to Medical Dictionary for Regulatory Activities (MedDRA) version 20 and graded for severity according to the NCI Common Terminology Criteria for Adverse Events (CTCAE).
- Maximum tolerated dose (MTD) [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]Defined as the dose at which fewer than one-third of participants experience a DLT or the highest dose at which no more than one instance of DLT is observed among 6 participants treated.
- Incidence of treatment-related adverse events (AE) [ Time Frame: From initiation of study treatment until 30 days after completion of study treatment, up to 1 year ]Adverse events will be classified using MedDRA version 20.0 and graded for severity using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Will be summarized with descriptive statistics.
- Abexinostat: Maximum concentration (Cmax) [ Time Frame: Cycle 1, Days 1 and 11; Cycle 2, Day 11 (each cycle is 28 days) ]Serum samples will be collected in order to obtain the Cmax of abexinostat over the course of 2 cycles under the following schedule: Pre-dose, immediately post-admin, 4 hrs (+/- 30 min) post-start of drug administration, and after completion of study drug administration on Cycle 1, Day 11 and Cycle 2, Day 11
- Abexinostat: Trough concentration (Ctrough) [ Time Frame: Cycle 1, Days 1 and 11; Cycle 2, Day 11 (each cycle is 28 days) ]Serum samples will be collected in order to obtain the Ctrough of abexinostat over the course of 2 cycles under the following schedule: Pre-dose, immediately post-admin, 4 hrs (+/- 30 min) post-start of drug administration, and after completion of study drug administration on Cycle 1, Day 11 and Cycle 2, Day 11
- Objective response rates (ORR) [ Time Frame: Up to 1 year ]An objective response is defined as Complete Response (CR), Partial Response (PR), assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 from initiation of study therapy until disease progression or study discontinuation, . ORR will be estimated using an exact method based on the binomial distribution (Clopper-Pearson interval) with a 90% confidence interval.
- Clinical benefit rate (CBR) [ Time Frame: Up to 6 months ]CBR is defined as the proportion of participants who displayed a clinical benefit (CR, PR, or Stable Disease (SD)) per RECIST v 1.1 and without disease progression at 6 months after initiation of study therapy.
- Median progression-free survival (PFS) [ Time Frame: Up to 1 year ]PFS will be determined according to RECIST v 1.1 and measured as the time from first objective response after initiation of study therapy until the time of progression or death, which ever occurs first . Will be estimated using Kaplan-Meier analysis.
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): NCT04498520
|Contact: Denisha Otisemail@example.com|
|United States, California|
|University of California, San Francisco|
|San Francisco, California, United States, 94115|
|Contact: Denisha Otis 877-827-3222 firstname.lastname@example.org|
|Principal Investigator: Pamela N. Munster, MD|
|United States, Florida|
|Moffitt Cancer Center|
|Tampa, Florida, United States, 33612|
|Contact: Ricardo L. Costa, MD, MSc 813-745-6100|
|Principal Investigator: Ricardo L. Costa, MD, MSc|
|Principal Investigator:||Pamela N Munster, MD||University of California, San Francisco|