Trials / Withdrawn
WithdrawnNCT04498520
Abexinostat, Palbociclib, and Fulvestrant for the Treatment of Breast or Gynecologic Cancer
Phase I Trial of Abexinostat Combined With Palbociclib and Fulvestrant in Patients With Antiestrogen Refractory ER+, HER2- Breast Cancer and Gynecological Metastatic Tumors
- Status
- Withdrawn
- Phase
- Phase 1
- Study type
- Interventional
- Enrollment
- 0 (actual)
- Sponsor
- Pamela Munster · Academic / Other
- Sex
- All
- Age
- 18 Years
- Healthy volunteers
- Not accepted
Summary
This phase I trial investigates the side effects and best dose of abexinostat and palbociclib when given together with fulvestrant in treating patients with breast or gynecologic cancer. Abexinostat may prevent tumor cells from growing and multiplying and may kill tumor cells. Palbociclib may prevent or slow the growth of tumor cells when used with other anti-hormonal therapy. Estrogen can cause the growth of breast and gynecologic tumor cells. Fulvestrant may help fight breast or gynecologic cancer by blocking the use of estrogen by the tumor cells. Giving abexinostat, palbociclib, and fulvestrant may work better in treating patients with breast or gynecologic cancer.
Detailed description
PRIMARY OBJECTIVES: 1. To determine the safety and tolerability of abexinostat tosylate (abexinostat) and palbociclib in combination with fulvestrant. 2. To determine the maximum tolerated dose (MTD) for abexinostat and palbociclib when combined with fulvestrant at standard dose. SECONDARY OBJECTIVES: 1. To describe the pharmacokinetics associated with abexinostat. 2. 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. 3. 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. EXPLORATORY OBJECTIVES: 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. 2. 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.
Conditions
- 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
Interventions
| Type | Name | Description |
|---|---|---|
| DRUG | Abexinostat Tosylate | Given PO |
| DRUG | Fulvestrant | Given IM |
| DRUG | Palbociclib | Given PO |
Timeline
- Start date
- 2021-03-31
- Primary completion
- 2025-06-30
- Completion
- 2025-06-30
- First posted
- 2020-08-04
- Last updated
- 2021-05-18
Regulatory
- FDA-regulated drug study
Source: ClinicalTrials.gov record NCT04498520. Inclusion in this directory is not an endorsement.