Ruxolitinib Phosphate, Paclitaxel, and Carboplatin in Treating Patients with Stage III-IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Status: Active

Description

This phase I / II partially randomized trial studies the side effects and the best dose of ruxolitinib phosphate when given together with paclitaxel and carboplatin and to see how well they work in treating patients with stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer. Ruxolitinib phosphate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ruxolitinib phosphate together with paclitaxel and carboplatin may be a better treatment for epithelial ovarian, fallopian tube, or primary peritoneal cancer compared to paclitaxel and carboplatin alone.

Eligibility Criteria

Inclusion Criteria

  • Patients must have clinically and radiographically suspected and previously untreated International Federation of Gynecologic and Obstetrics (FIGO) stage III or IV epithelial ovarian, primary peritoneal or fallopian tube cancer, high grade, for whom the plan of management will include neoadjuvant chemotherapy (NACT) with interval tumor reductive surgery (TRS) who have undergone biopsies for histologic confirmation
  • Institutional confirmation of Mullerian epithelial adenocarcinoma on core biopsy (not cytology or fine needle aspiration) or laparoscopic biopsy; (for phase II of the study formalin-fixed paraffin-embedded [FFPE] tissue should be available for laboratory analysis); patients with the following histologic epithelial cell types are eligible: high grade serous carcinoma, high grade endometrioid carcinoma, clear cell carcinoma, or a combination of these
  • All patients must have measurable disease as defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI
  • Appropriate stage for study entry based on the following diagnostic workup: * History/physical examination within 28 days prior to registration * Radiographic imaging of the chest, abdomen and pelvis within 28 days prior to registration documenting disease consistent with FIGO stage III or IV disease * Further protocol-specific assessments
  • Eastern Cooperative Oncology Group (ECOG)/Karnofsky performance status of 0, 1, or 2 within 28 days prior to registration
  • Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl; this ANC cannot have been induced by granulocyte colony stimulating factors (within 14 days prior to registration)
  • Platelets greater than or equal to 100,000/mcl (within 14 days prior to registration)
  • Hemoglobin greater than 9.0 mg/dl (transfusions are permitted to achieve baseline hemoglobin level) (within 14 days prior to registration)
  • Estimated creatinine clearance (CrCl) >= 50 mL/min according to the Cockcroft-Gault formula (within 14 days prior to registration)
  • Bilirubin =< 1.5 x upper limit of normal (ULN) (within 14 days prior to registration)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN (within 14 days prior to registration)
  • Alkaline phosphatase =< 2.5 x ULN (within 14 days prior to registration)
  • Neurologic function: neuropathy (sensory and motor) less than or equal to Common Terminology Criteria for Adverse Events (CTCAE) grade 1
  • Ability to swallow and retain oral medication
  • The patient must provide study-specific informed consent prior to study entry
  • BRCA testing results (i.e., comprehensive BRCA1 and BRCA2 sequencing, including assessment of gene rearrangements) must be submitted for all patients enrolled to Amendment 7 and subsequent amendments; BRCA testing results are optional for all patients enrolled prior to Amendment 7; due to the long acceptance of germline BRCA testing through Myriad, Myriad testing reports will be accepted without additional documentation; if testing for germline BRCA is done by other organizations, in addition to the testing report, documentation from a qualified medical professional (e.g., ovarian cancer specialty physician involved in the field, high risk genetics physician, genetics counselor) detailing the laboratory results is required; please retain a copy of all reports (positive, variants of unknown significance [VUS], or negative)

Exclusion Criteria

  • Patients with suspected non-gynecologic malignancy, such as gastrointestinal
  • Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies are excluded if there is any evidence of other malignancy being present within the last three years (2 years for breast cancer); patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
  • Patients who have received prior chemotherapy for any abdominal or pelvic tumor within the last three years are excluded; patients may have received prior adjuvant chemotherapy and radiotherapy for localized breast cancer, provided that it was completed more than 2 years prior to registration, the patient remains free of recurrent or metastatic disease and hormonal therapy has been discontinued
  • Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis or thoracic cavity within the last three years are excluded; prior radiation for localized cancer of the head and neck or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
  • Patients who have received any targeted therapy (including but not limited to vaccines, antibodies, tyrosine kinase inhibitors) or hormonal therapy for management of their epithelial ovarian, fallopian tube or peritoneal primary cancer
  • Patients with mucinous carcinoma, low grade endometrioid carcinoma, low grade serous carcinoma or carcinosarcoma
  • Patients with synchronous primary endometrial cancer, or a past history of primary endometrial cancer, unless all of the following conditions are met: stage not greater than I-A, grade 1 or 2, no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including serous, clear cell or other FIGO grade 3 lesions
  • Severe, active co-morbidity defined as follows: * Chronic or current active infectious disease requiring systemic antibiotics, antifungal or antiviral treatment * Known brain or central nervous system metastases or history of uncontrolled seizures * Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months from enrollment, New York Heart Association class III or IV congestive heart failure, and serious arrhythmia requiring medication (this does not include asymptomatic atrial fibrillation with controlled ventricular rate) * Partial or complete gastrointestinal obstruction
  • Patients who are not candidates for major abdominal surgery due to known medical comorbidities
  • Patients with any condition that in the judgment of the investigator would jeopardize safety or patient compliance with the protocol
  • Patients who are unwilling to be transfused with blood components
  • Concurrent anticancer therapy (e.g. chemotherapy, radiation therapy, biologic therapy, immunotherapy, hormonal therapy, investigational therapy)
  • Receipt of an investigational study drug for any indication within 30 days or 5 half-lives (whichever is longer) prior to day 1 of protocol therapy
  • Patients who, in the opinion of the investigator, are unable or unlikely to comply with the dosing schedule and study evaluations
  • Patients who are pregnant or nursing; the effects of ruxolitinib on the developing human fetus are unknown; for this reason, women of child-bearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; WOCBP must have a screening negative serum or urine pregnancy test within 14 days of registration; a second pregnancy test must be done within 24 hours prior to the start of the first cycle of study treatment; women must not be breastfeeding * Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) do not require contraception * Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy and/or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 month amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level greater than 40mIU/mL
  • Known history of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection or known history of tuberculosis; (This exclusion criterion is necessary because the treatments involved in this protocol may be immunosuppressive)

Locations & Contacts

California

Auburn
Sutter Auburn Faith Hospital
Status: Active
Contact: Site Public Contact
Phone: 415-209-2686
Email: bernicl@sutterhealth.org
La Jolla
UC San Diego Moores Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 858-822-5354
Email: cancercto@ucsd.edu
Roseville
Sutter Roseville Medical Center
Status: Active
Contact: Site Public Contact
Phone: 415-209-2686
Email: bernicl@sutterhealth.org
Sacramento
Sutter Medical Center Sacramento
Status: Active
Contact: Site Public Contact
Phone: 415-209-2686
Email: bernicl@sutterhealth.org
San Francisco
California Pacific Medical Center-Pacific Campus
Status: Active
Contact: Site Public Contact
Phone: 415-209-2686
Email: bernicl@sutterhealth.org

Connecticut

Danbury
Danbury Hospital
Status: Active
Contact: Site Public Contact
Phone: 203-739-8074
Norwalk
Norwalk Hospital
Status: Active
Contact: Site Public Contact
Phone: 203-852-2996
Email: jennifer.long@norwalkhealth.org

Delaware

Newark
Christiana Care Health System-Christiana Hospital
Status: Active
Contact: Site Public Contact
Phone: 302-623-4450
Email: KDempsey@christianacare.org
Helen F Graham Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 302-623-4450
Email: KDempsey@christianacare.org
Rehoboth Beach
Beebe Health Campus
Status: Active
Contact: Site Public Contact
Phone: 302-645-3100
Email: Dmiskin@Beebehealthcare.org

Florida

Sarasota
Sarasota Memorial Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 941-917-2225

Georgia

Atlanta
Northside Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 404-303-3355
Email: ClinicalTrials@northside.com
Augusta
Augusta University Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 706-721-2388
Email: ga_cares@augusta.edu
Savannah
Lewis Cancer and Research Pavilion at Saint Joseph's / Candler
Status: Active
Contact: Site Public Contact
Phone: 912-819-5704
Email: underberga@sjchs.org
Memorial Health University Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 912-350-7887
Email: clayter1@memorialhealth.com
Summit Cancer Care-Candler
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 412-339-5294
Email: Roster@nrgoncology.org

Illinois

Chicago
John H Stroger Jr Hospital of Cook County
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 312-864-5204
Northwestern University
Status: Active
Contact: Site Public Contact
Phone: 312-695-1301
Email: cancer@northwestern.edu
University of Chicago Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 773-702-8222
Email: cancerclinicaltrials@bsd.uchicago.edu
Danville
Carle on Vermilion
Status: Active
Contact: Site Public Contact
Phone: 800-446-5532
Email: Research@carle.com
Effingham
Carle Physician Group-Effingham
Status: Active
Contact: Site Public Contact
Phone: 800-446-5532
Email: Research@carle.com
Lake Forest
Northwestern Medicine Lake Forest Hospital
Status: Active
Contact: Site Public Contact
Email: cancertrials@northwestern.edu
Mattoon
Carle Physician Group-Mattoon / Charleston
Status: Active
Contact: Site Public Contact
Phone: 800-446-5532
Email: Research@carle.com
Orland Park
University of Chicago Medicine-Orland Park
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 773-702-8222
Email: cancerclinicaltrials@bsd.uchicago.edu
Urbana
Carle Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-446-5532
Email: Research@carle.com
The Carle Foundation Hospital
Status: Active
Contact: Site Public Contact
Phone: 800-446-5532
Email: Research@carle.com

Indiana

Fort Wayne
Parkview Regional Medical Center
Status: Active
Contact: Site Public Contact
Phone: 877-784-4673
Indianapolis
Saint Vincent Hospital and Health Care Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 317-338-2194
Email: research@stvincent.org

Iowa

Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-237-1225

Kentucky

Louisville
Norton Hospital Pavilion and Medical Campus
Status: Active
Contact: Site Public Contact
Phone: 502-629-2500
Norton Suburban Hospital and Medical Campus
Status: Active
Contact: Site Public Contact
Phone: 502-629-3465

Louisiana

Covington
Women's Cancer Care-Covington
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 225-215-1353
Email: clinicalresearch@marybird.com
New Orleans
Ochsner Medical Center Jefferson
Status: Active
Contact: Site Public Contact
Phone: 504-703-8712
Email: Gregory.Johnstone@ochsner.org

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 410-955-8804
Email: jhcccro@jhmi.edu

Massachusetts

Worcester
University of Massachusetts Memorial Health Care
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 508-856-6265

Michigan

Brownstown
Henry Ford Cancer Institute-Downriver
Status: Active
Contact: Site Public Contact
Phone: 313-916-3721
Email: CTOResearch@hfhs.org
Dearborn
Henry Ford Medical Center-Fairlane
Status: Active
Contact: Site Public Contact
Phone: 313-916-3721
Email: CTOResearch@hfhs.org
Detroit
Henry Ford Hospital
Status: Active
Contact: Site Public Contact
Phone: 313-916-3721
Email: CTOResearch@hfhs.org
Grand Rapids
Spectrum Health at Butterworth Campus
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Kalamazoo
West Michigan Cancer Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Novi
Henry Ford Medical Center-Columbus
Status: Active
Contact: Site Public Contact
Phone: 313-916-3721
Email: CTOResearch@hfhs.org
Traverse City
Munson Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
West Bloomfield
Henry Ford West Bloomfield Hospital
Status: Active
Contact: Site Public Contact
Phone: 313-916-3721
Email: CTOResearch@hfhs.org

Minnesota

Burnsville
Fairview Ridges Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Edina
Fairview-Southdale Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Maple Grove
Fairview Maple Grove Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Minneapolis
Abbott-Northwestern Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Saint Louis Park
Park Nicollet Clinic - Saint Louis Park
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Saint Paul
Regions Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
United Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Woodbury
Minnesota Oncology Hematology PA-Woodbury
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com

Missouri

Saint Louis
Barnes-Jewish Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-600-3606
Email: info@ccadmin.wustl.edu
Washington University School of Medicine
Status: Active
Contact: Site Public Contact
Phone: 800-600-3606
Email: info@siteman.wustl.edu
Springfield
CoxHealth South Hospital
Status: Active
Contact: Site Public Contact
Phone: 417-269-4520
Mercy Hospital Springfield
Status: Active
Contact: Site Public Contact
Phone: 417-269-4520

Nebraska

Omaha
Nebraska Methodist Hospital
Status: Active
Contact: Site Public Contact
Phone: 402-354-5144

Nevada

Las Vegas
Women's Cancer Center of Nevada
Status: Active
Contact: Site Public Contact
Phone: 702-693-6870
Email: kmcwhirter@wccenter.com

New Jersey

Hackensack
Hackensack University Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 201-996-2879

New Mexico

Albuquerque
Southwest Gynecologic Oncology Associates Inc
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 505-272-0530
Email: RDraper@nmcca.org
University of New Mexico Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 505-925-0366
Email: LByatt@nmcca.org

New York

Buffalo
Roswell Park Cancer Institute
Status: Active
Contact: Site Public Contact
Phone: 800-767-9355
Email: askroswell@roswellpark.org
Rochester
University of Rochester
Status: Active
Contact: Site Public Contact
Phone: 585-275-5830

North Carolina

Winston-Salem
Wake Forest University Health Sciences
Status: Active
Contact: Site Public Contact
Phone: 336-713-6771

Ohio

Centerville
Miami Valley Hospital South
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 937-775-1350
Email: som_dcop@wright.edu
Cleveland
Cleveland Clinic Cancer Center / Fairview Hospital
Status: Active
Contact: Site Public Contact
Phone: 866-223-8100
Email: CancerAnswer@ccf.org
Cleveland Clinic Foundation
Status: Active
Contact: Site Public Contact
Phone: 866-223-8100
Email: CancerAnswer@ccf.org
Columbus
Riverside Methodist Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 614-566-4475
Email: sheree@columbusccop.org
The Mark H Zangmeister Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 614-488-2118
Email: sheree@columbusccop.org
Mayfield Heights
Hillcrest Hospital Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 866-223-8100
Email: CancerAnswer@ccf.org

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 405-271-8777
Email: ou-clinical-trials@ouhsc.edu

Oregon

Portland
Legacy Good Samaritan Hospital and Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-220-4937
Email: cancer@lhs.org
Tualatin
Legacy Meridian Park Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 503-413-1742

Pennsylvania

Philadelphia
University of Pennsylvania / Abramson Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-474-9892
Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 412-647-8073
Willow Grove
Abington Memorial Hospital-Asplundh Cancer Pavilion
Status: Active
Contact: Site Public Contact
Phone: 215-481-2402

Rhode Island

Providence
Women and Infants Hospital
Status: Active
Contact: Site Public Contact
Phone: 401-274-1122

Tennessee

Nashville
Vanderbilt University / Ingram Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-811-8480

Texas

Dallas
Parkland Memorial Hospital
Status: Active
Contact: Site Public Contact
Phone: 214-590-5582
Email: canceranswerline@UTSouthwestern.edu
UT Southwestern / Simmons Cancer Center-Dallas
Status: Active
Contact: Site Public Contact
Phone: 214-648-7097
Email: canceranswerline@UTSouthwestern.edu

Virginia

Charlottesville
University of Virginia Cancer Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 434-243-6303
Email: PAS9E@virginia.edu

Washington

Seattle
Fred Hutchinson Cancer Research Center
Status: Active
Contact: Site Public Contact
Phone: 800-804-8824
Seattle Cancer Care Alliance
Status: Active
Contact: Site Public Contact
Phone: 800-804-8824
University of Washington Medical Center
Status: Active
Contact: Site Public Contact
Phone: 800-804-8824
Vancouver
Legacy Salmon Creek Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 503-413-2150

West Virginia

Charleston
West Virginia University Charleston Division
Status: Active
Contact: Site Public Contact
Phone: 304-388-9944

Wisconsin

Eau Claire
Marshfield Medical Center-EC Cancer Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-782-8581
Email: oncology.clinical.trials@marshfieldresearch.org
Madison
University of Wisconsin Hospital and Clinics
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-622-8922
Marshfield
Marshfield Medical Center-Marshfield
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-782-8581
Email: oncology.clinical.trials@marshfieldresearch.org
Milwaukee
Froedtert and the Medical College of Wisconsin
Status: Active
Contact: Site Public Contact
Phone: 414-805-4380
Minocqua
Marshfield Clinic-Minocqua Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-782-8581
Email: oncology.clinical.trials@marshfieldresearch.org
Rice Lake
Marshfield Medical Center-Rice Lake
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-782-8581
Email: oncology.clinical.trials@marshfieldresearch.org
Stevens Point
Marshfield Clinic Stevens Point Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-782-8581
Email: oncology.clinical.trials@marshfieldresearch.org
Wausau
Marshfield Clinic-Wausau Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-782-8581
Email: oncology.clinical.trials@marshfieldresearch.org
Weston
Marshfield Clinic - Weston Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-782-8581
Email: oncology.clinical.trials@marshfieldresearch.org

Trial Objectives and Outline

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.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
NRG Oncology

Principal Investigator
Robert Allen Burger

Trial IDs

Primary ID NRG-GY007
Secondary IDs NCI-2016-00203
Clinicaltrials.gov ID NCT02713386