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

A Phase I/II Study of Ruxolitinib With Front-Line Neoadjuvant and Post-Surgical Therapy in Patients With Advanced Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer

This phase I/II 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Ovarian Endometrioid Adenocarcinoma; Ovarian Clear Cell Adenocarcinoma; Primary Peritoneal High Grade Serous Adenocarcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Stage III Fallopian Tube Cancer AJCC v7; Stage III Primary Peritoneal Cancer AJCC v7; Stage IIIA Fallopian Tube Cancer AJCC v7; Stage IIIA Primary Peritoneal Cancer AJCC v7; Stage IIIB Fallopian Tube Cancer AJCC v7; Stage IIIB Primary Peritoneal Cancer AJCC v7; Stage IIIC Fallopian Tube Cancer AJCC v7; Stage IIIC Primary Peritoneal Cancer AJCC v7; Stage IV Fallopian Tube Cancer AJCC v6 and v7; Stage IV Primary Peritoneal Cancer AJCC v7; Ovarian High Grade Serous Adenocarcinoma; Fallopian Tube High Grade Serous Adenocarcinoma; Primary Peritoneal Endometrioid Adenocarcinoma; FIGO Stage III Ovarian Cancer; FIGO Stage IIIA Ovarian Cancer; FIGO Stage IIIA1 Ovarian Cancer; FIGO Stage IIIA2 Ovarian Cancer; FIGO Stage IIIB Ovarian Cancer; FIGO Stage IIIC Ovarian Cancer; FIGO Stage IVA Ovarian Cancer; FIGO Stage IVB Ovarian Cancer
• Intervention / Treatment: Drug: Carboplatin; Drug: Paclitaxel; Drug: Ruxolitinib Phosphate; Procedure: Therapeutic Conventional Surgery

Detailed 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. 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.

• Study Type: Interventional
• Enrollment (Anticipated): 147
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Goodyear, Arizona, United States, 85338
      • CTCA at Western Regional Medical Center
  • California
    • Auburn, California, United States, 95602
      • Sutter Auburn Faith Hospital
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90095
      • UCLA / Jonsson Comprehensive Cancer Center
    • Roseville, California, United States, 95661
      • Sutter Roseville Medical Center
    • Sacramento, California, United States, 95816
      • Sutter Medical Center Sacramento
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center-Pacific Campus
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Danbury Hospital
    • Norwalk, Connecticut, United States, 06856
      • Norwalk Hospital
  • Delaware
    • Newark, Delaware, United States, 19713
      • Helen F Graham Cancer Center
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
    • Rehoboth Beach, Delaware, United States, 19971
      • Beebe Health Campus
  • Florida
    • Sarasota, Florida, United States, 34239
      • Sarasota Memorial Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
    • Augusta, Georgia, United States, 30912
      • Augusta University Medical Center
    • Savannah, Georgia, United States, 31405
      • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
    • Savannah, Georgia, United States, 31404
      • Memorial Health University Medical Center
    • Savannah, Georgia, United States, 31405
      • Summit Cancer Care-Candler
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Chicago, Illinois, United States, 60612
      • John H Stroger Jr Hospital of Cook County
    • Danville, Illinois, United States, 61832
      • Carle on Vermilion
    • Effingham, Illinois, United States, 62401
      • Carle Physician Group-Effingham
    • Lake Forest, Illinois, United States, 60045
      • Northwestern Medicine Lake Forest Hospital
    • Mattoon, Illinois, United States, 61938
      • Carle Physician Group-Mattoon/Charleston
    • New Lenox, Illinois, United States, 60451
      • UC Comprehensive Cancer Center at Silver Cross
    • Orland Park, Illinois, United States, 60462
      • University of Chicago Medicine-Orland Park
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
    • Urbana, Illinois, United States, 61801
      • The Carle Foundation Hospital
    • Zion, Illinois, United States, 60099
      • Midwestern Regional Medical Center
  • Indiana
    • Fort Wayne, Indiana, United States, 46845
      • Parkview Regional Medical Center
    • Indianapolis, Indiana, United States, 46260
      • Saint Vincent Hospital and Health Care Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Hospital Pavilion and Medical Campus
    • Louisville, Kentucky, United States, 40207
      • Norton Suburban Hospital and Medical Campus
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Mary Bird Perkins Cancer Center
    • Baton Rouge, Louisiana, United States, 70817
      • Woman's Hospital
    • Covington, Louisiana, United States, 70433
      • Women's Cancer Care-Covington
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center Jefferson
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • UMass Memorial Medical Center - Memorial Division
  • Michigan
    • Brownstown, Michigan, United States, 48183
      • Henry Ford Cancer Institute-Downriver
    • Dearborn, Michigan, United States, 48126
      • Henry Ford Medical Center-Fairlane
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health at Butterworth Campus
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Novi, Michigan, United States, 48377
      • Henry Ford Medical Center-Columbus
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • West Bloomfield, Michigan, United States, 48322
      • Henry Ford West Bloomfield Hospital
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Maple Grove, Minnesota, United States, 55369
      • Fairview Clinics and Surgery Center Maple Grove
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology PA-Woodbury
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63110
      • Barnes-Jewish Hospital
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Women's Cancer Center of Nevada
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
    • Somerville, New Jersey, United States, 08876
      • Robert Wood Johnson University Hospital Somerset
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico Cancer Center
    • Albuquerque, New Mexico, United States, 87106
      • Southwest Gynecologic Oncology Associates Inc
    • Rio Rancho, New Mexico, United States, 87124
      • Presbyterian Rust Medical Center/Jorgensen Cancer Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • UHHS-Chagrin Highlands Medical Center
    • Centerville, Ohio, United States, 45459
      • Miami Valley Hospital South
    • Chardon, Ohio, United States, 44024
      • Geauga Hospital
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Cancer Center/Fairview Hospital
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43219
      • The Mark H Zangmeister Center
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Hospital Cancer Center
    • Westlake, Ohio, United States, 44145
      • UHHS-Westlake Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Portland, Oregon, United States, 97210
      • Legacy Good Samaritan Hospital and Medical Center
    • Tualatin, Oregon, United States, 97062
      • Legacy Meridian Park Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania/Abramson Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Pennsylvania Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute (UPCI)
    • Willow Grove, Pennsylvania, United States, 19090
      • Asplundh Cancer Pavilion
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women and Infants Hospital
  • South Carolina
    • Hilton Head Island, South Carolina, United States, 29926-3827
      • South Carolina Cancer Specialists PC
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University/Ingram Cancer Center
  • Texas
    • Dallas, Texas, United States, 75235
      • Parkland Memorial Hospital
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center-Dallas
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center - Montlake
    • Vancouver, Washington, United States, 98686
      • Legacy Salmon Creek Hospital
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • West Virginia University Charleston Division
  • Wisconsin
    • Eau Claire, Wisconsin, United States, 54701
      • Marshfield Medical Center-EC Cancer Center
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Medical Center-Marshfield
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Minocqua, Wisconsin, United States, 54548
      • Marshfield Clinic-Minocqua Center
    • Rice Lake, Wisconsin, United States, 54868
      • Marshfield Medical Center-Rice Lake
    • Stevens Point, Wisconsin, United States, 54482
      • Marshfield Clinic Stevens Point Center
    • Wausau, Wisconsin, United States, 54401
      • Marshfield Clinic-Wausau Center
    • Weston, Wisconsin, United States, 54476
      • Marshfield Medical Center - Weston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I (paclitaxel and carboplatin); See Detailed Description.	Drug: Carboplatin; Given IV; Other Names: Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carboplatinum; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo; Drug: Paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat; Procedure: Therapeutic Conventional Surgery; Undergo TRS
Experimental: Arm II (ruxolitinib, paclitaxel, and carboplatin); See Detailed Description.	Drug: Carboplatin; Given IV; Other Names: Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carboplatinum; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo; Drug: Paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat; Drug: Ruxolitinib Phosphate; Given PO; Other Names: Jakafi; INCB-18424 Phosphate; Procedure: Therapeutic Conventional Surgery; Undergo TRS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of hematologic (heme) dose-limiting toxicity (Phase I)	Will be assessed according to Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (CTCAE version 5.0 will be used starting 04/01/2018).	42 days (2 cycles)
Progression-free survival (PFS) (Phase II)	Will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. A log-rank test utilizing the categorized values of the exploratory laboratory parameters or a Cox proportional hazards (PH) model to estimate of the hazard ratio for progression or death in PFS. If feasible, the PH model will examine the effect of continuous measures.	From study entry to time of progression or death, whichever occurs first, assessed up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events (Phase I)	Will be assessed according to CTEP CTCAE version 4.03 (CTCAE version 5.0 will be used starting 04/01/2018).	Up to 5 years
Frequency of patients who could not receive surgery within the defined timeframe for reasons other than non-response, disease progression, or medical contraindications (Phase I)	Frequencies will be given by the dose-level administered.	Up to 6 weeks
Number of patients who discontinue ruxolitinib in the first 3 months of maintenance therapy due to toxicity (Phase I)		Up to 3 months in the maintenance phase
Progression-free survival (PFS) (Phase II)	Will be assessed according to RECIST 1.1. Subset analyses within categorized, important exploratory laboratory parameters will examine the treatment effect on PFS. The effect of treatment on PFS will be examined within each of these subsets using a log-rank test or a Cox PH model. Interest will center on whether the hazard of PFS changes from one group to another. The impact of the biomarkers on PFS will be assessed using log-rank tests or Cox PH models.	From study entry to time of progression or death, whichever occurs first, assessed up to 5 years
Proportion of patients who have total gross resection (Phase II)	Will be defined as no visible or palpable tumor remaining after completion of surgery. Differences in the proportion who have total gross resection by treatment arm will be examined with Fisher's Exact Test. The results of this analysis will be presented in terms of the odds ratio (maximum-likelihood estimations and confidence intervals). Multivariate logistic modeling will be conducted if feasible.	At the time of surgery
Complete pathological response (Phase II)	Will be defined as no evidence of disease on radiographic imaging at the time of radiographic tumor measurement. Differences in the proportion who have complete pathological response by treatment arm will be examined with Fisher's Exact Test. Multivariate logistic modeling will be conducted if feasible.	Up to 5 years
Overall survival (OS) (Phase II)	The effect of treatment on OS will be conducted with the log-rank statistic and characterized with a Cox PH model. The impact of the biomarkers on OS will be assessed using log-rank tests or Cox PH models.	From randomization until death or date last seen, assessed up to 5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cancer stem cells (CSC) observed in tissue	Landmark analyses will be conducted to see if changes in CSC are associated with PFS. The predictive value of CSC will be formally examined with a Cox model using an interaction term with treatment. Subset analyses will be conducted as well in the event that a formal analysis fails to reject the null hypothesis.	Baseline up to 63 days (3 cycles)
Change in serum C-reactive protein (CRP)	The impact of baseline values on PFS and OS can be assessed for prognostic and predictive significance with log-rank statistics and Cox models. The impact of changes in CRP values on PFS and OS can be examined with landmark analyses or as time dependent covariates.	Baseline up to 63 days (3 cycles)

Collaborators and Investigators

• Sponsor: NRG Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Charles N Landen, NRG Oncology

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2016
• Primary Completion (Actual): September 30, 2021
• Study Completion (Anticipated): September 30, 2022

Study Registration Dates

• First Submitted: March 15, 2016
• First Submitted That Met QC Criteria: March 15, 2016
• First Posted (Estimate): March 18, 2016

Study Record Updates

• Last Update Posted (Actual): June 2, 2022
• Last Update Submitted That Met QC Criteria: June 1, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Peritoneal Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Digestive System Neoplasms; Endocrine Gland Neoplasms; Fallopian Tube Diseases; Abdominal Neoplasms; Cystadenocarcinoma; Neoplasms, Cystic, Mucinous, and Serous; Endometrial Neoplasms; Adenocarcinoma; Ovarian Neoplasms; Fallopian Tube Neoplasms; Peritoneal Neoplasms; Carcinoma, Ovarian Epithelial; Cystadenocarcinoma, Serous; Carcinoma, Endometrioid; Adenocarcinoma, Clear Cell; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel; Albumin-Bound Paclitaxel
• Other Study ID Numbers: NRG-GY007 (Other Identifier: CTEP); U10CA180868 (U.S. NIH Grant/Contract); NCI-2016-00203 (Registry Identifier: CTRP (Clinical Trial Reporting Program))