Recruitment

Recruitment Status
Active, not recruiting
Estimated Enrollment
158

Summary

Conditions
  • Fallopian Tube Clear Cell Adenocarcinoma
  • Fallopian Tube Endometrioid Adenocarcinoma
  • FIGO Stage III Ovarian Cancer
  • Ovarian Clear Cell Adenocarcinoma
  • Stage IIIB Primary Peritoneal Cancer AJCC v7
  • Stage IIIB Fallopian Tube Cancer AJCC v7
  • Primary Peritoneal High Grade Serous Adenocarcinoma
  • Stage III Fallopian Tube Cancer AJCC v7
  • FIGO Stage IIIA Ovarian Cancer
  • Stage IIIC Fallopian Tube Cancer AJCC v7
  • Primary Peritoneal Endometrioid Adenocarcinoma
  • Stage IV Primary Peritoneal Cancer AJCC v7
  • FIGO Stage IIIA1 Ovarian Cancer
  • FIGO Stage IIIA2 Ovarian Cancer
  • FIGO Stage IIIB Ovarian Cancer
  • FIGO Stage IIIC Ovarian Cancer
  • Stage IIIC Primary Peritoneal Cancer AJCC v7
  • Stage IV Fallopian Tube Cancer AJCC v6 and v7
  • High Grade Ovarian Serous Adenocarcinoma
  • Stage IIIA Fallopian Tube Cancer AJCC v7
  • Stage IIIA Primary Peritoneal Cancer AJCC v7
  • Stage III Primary Peritoneal Cancer AJCC v7
  • FIGO Stage IVA Ovarian Cancer
  • FIGO Stage IVB Ovarian Cancer
  • Ovarian Endometrioid Adenocarcinoma
  • High Grade Fallopian Tube Serous Adenocarcinoma
Type
Interventional
Phase
Phase 1Phase 2
Design
Allocation: RandomizedIntervention Model: Parallel AssignmentMasking: None (Open Label)Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 125 years
Gender
Only males

Description

PRIMARY OBJECTIVES: I. Determine whether treatment with ruxolitinib phosphate (ruxolitinib) in combination with conventional neoadjuvant and post-surgical chemotherapy is safe and tolerable in the primary therapy for epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. (Phase I) II. ...

PRIMARY OBJECTIVES: I. Determine whether treatment with ruxolitinib phosphate (ruxolitinib) in combination with conventional neoadjuvant and post-surgical chemotherapy is safe and tolerable in the primary therapy for epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. (Phase I) II. Demonstrate whether treatment with ruxolitinib in combination with conventional neoadjuvant and post-surgical chemotherapy results in a prolonged progression-free survival when compared to chemotherapy alone, in primary therapy for epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. (Phase II) SECONDARY OBJECTIVES: I. Determine frequency of patients who do not receive surgery within 6 weeks of completing cycle 3 therapy for reasons other than non-response, disease progression, or medical contraindications. (Phase I) II. Determine if continuation of ruxolitinib as maintenance therapy in participants who complete 6 cycles of standard chemotherapy in combination with ruxolitinib and have not experienced unacceptable toxicity or disease progression is safe and tolerable. (Phase I) III. Determine the impact of ruxolitinib in combination with chemotherapy on progression-free survival as a function of proposed exploratory biomarkers - ALDH+ CD133+ (possibly also CD24+ CK19+) co-staining by AQUA immunofluorescence (IF); ratio of tumor expression of CD8:FOXP3 by immunohistochemistry (IHC); and tumor CD3, CD4, TAI-1, HLA class I and II, CD68 expression by IHC in archived tumor tissue, BRCA status, and serum C-reactive protein (CRP) and IL-6 levels in pre-treatment serum. (Phase II) IV. Investigate the prognostic significance of exploratory laboratory parameters in terms of both progression-free survival and overall survival in women receiving conventional chemotherapy alone. (Phase II) V. Determine whether treatment with ruxolitinib in combination with conventional chemotherapy is associated with total gross resection rate at time of interval cytoreductive surgery. (Phase II) VI. Determine whether treatment with ruxolitinib in combination with conventional chemotherapy is associated with complete pathologic response defined at interval cytoreductive surgery. (Phase II) VII. Demonstrate whether treatment with ruxolitinib in combination with conventional chemotherapy results in an improvement in overall survival in primary management of epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. (Phase II) OUTLINE: This is a phase I, dose-escalation study of ruxolitinib phosphate, followed by a phase II study. PHASE I PORTION OF STUDY IS COMPLETE (04/06/2018) PHASE I (CYCLES 1-3): Patients receive ruxolitinib phosphate orally (PO) twice daily (BID) on days 1-21, paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Within 6 weeks after completion of cycle 3, patients undergo tumor reductive surgery (TRS). PHASE I (CYCLES 4-6): Within 6 weeks of TRS, patients receive ruxolitinib phosphate PO BID on days 1-21, paclitaxel IV over 1 hour on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. If TRS is not performed due to non-response or medical contraindications and criteria for discontinuation of protocol therapy have not been met, patients should resume ruxolitinib phosphate, paclitaxel, and carboplatin within 6 weeks of completing cycle 3 of therapy. MAINTENANCE THERAPY: Within 3 weeks after completion of cycle 6, patients receive ruxolitinib phosphate PO BID. Treatment continues in the absence of disease progression or unacceptable toxicity. PHASE II: Patients are randomized to 1 of 2 treatment arms. ARM I (CYCLES 1-3): Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Within 6 weeks after completion of cycle 3, patients undergo TRS. ARM I (CYCLES 4-6): Within 4 weeks of surgery (or within 6 weeks of completion of cycle 3 in patients who do not undergo TRS), patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. ARM II (CYCLES 1-3): Patients receive ruxolitinib phosphate PO BID on days 1-21 and paclitaxel and carboplatin as in arm I. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Within 6 weeks after completion of cycle 3, patients undergo TRS. ARM II (CYCLES 4-6): Within 4 weeks of surgery (or within 6 weeks of completion of cycle 3 in patients who do not undergo TRS), patients receive ruxolitinib phosphate PO BID on days 1-21 and paclitaxel and carboplatin as in arm I. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients in phase I are followed up until resolution of adverse events, and patients in phase II are followed up every 3 months for 2 years and then every 6 months for 3 years.

Tracking Information

NCT #
NCT02713386
Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Robert A Burger NRG Oncology