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.