Fallopian Tube Clear Cell AdenocarcinomaPhase 1/2NCT02713386
Ruxolitinib Phosphate, Paclitaxel, and Carboplatin in Treating Patients With Stage III-IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
A Phase 1/2 study testing Carboplatin, Paclitaxel and Ruxolitinib Phosphate in people with Fallopian Tube Clear Cell Adenocarcinoma and Fallopian Tube Endometrioid Adenocarcinoma, run by NRG Oncology at 110 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Fallopian Tube Clear Cell Adenocarcinoma, Fallopian Tube Endometrioid Adenocarcinoma, Fallopian Tube High Grade Serous Adenocarcinoma
- What is being tested?
- Carboplatin, Paclitaxel and Ruxolitinib Phosphate
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 147 participants
- Where
- 110 sitesUnited States
- Study dates
- 14 Nov 2016to 22 May 2024
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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
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- 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)
Trial locations and contacts
110 sites in 1 country.
110 sites in 1 country
United States110 sites
Southwest Gynecologic Oncology Associates Inc
Albuquerque, New Mexico, 87106
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
Northside Hospital
Atlanta, Georgia, 30342
Sutter Auburn Faith Hospital
Auburn, California, 95602
Augusta University Medical Center
Augusta, Georgia, 30912
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Mary Bird Perkins Cancer Center
Baton Rouge, Louisiana, 70809
Woman's Hospital
Baton Rouge, Louisiana, 70817
UHHS-Chagrin Highlands Medical Center
Beachwood, Ohio, 44122
Henry Ford Cancer Institute-Downriver
Brownstown, Michigan, 48183
Roswell Park Cancer Institute
Buffalo, New York, 14263
Fairview Ridges Hospital
Burnsville, Minnesota, 55337
Miami Valley Hospital South
Centerville, Ohio, 45459
Geauga Hospital
Chardon, Ohio, 44024
West Virginia University Charleston Division
Charleston, West Virginia, 25304
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
Northwestern University
Chicago, Illinois, 60611
John H Stroger Jr Hospital of Cook County
Chicago, Illinois, 60612
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Case Western Reserve University
Cleveland, Ohio, 44106
MetroHealth Medical Center
Cleveland, Ohio, 44109
Cleveland Clinic Cancer Center/Fairview Hospital
Cleveland, Ohio, 44111
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Riverside Methodist Hospital
Columbus, Ohio, 43214
The Mark H Zangmeister Center
Columbus, Ohio, 43219
Mercy Hospital
Coon Rapids, Minnesota, 55433
Women's Cancer Care-Covington
Covington, Louisiana, 70433
Parkland Memorial Hospital
Dallas, Texas, 75235
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Danbury Hospital
Danbury, Connecticut, 06810
Carle at The Riverfront
Danville, Illinois, 61832
Henry Ford Medical Center-Fairlane
Dearborn, Michigan, 48126
Henry Ford Hospital
Detroit, Michigan, 48202
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, 54701
Fairview Southdale Hospital
Edina, Minnesota, 55435
Carle Physician Group-Effingham
Effingham, Illinois, 62401
Parkview Regional Medical Center
Fort Wayne, Indiana, 46845
CTCA at Western Regional Medical Center
Goodyear, Arizona, 85338
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Grand Rapids, Michigan, 49503
Hackensack University Medical Center
Hackensack, New Jersey, 07601
South Carolina Cancer Specialists PC
Hilton Head Island, South Carolina, 29926-3827
Ascension Saint Vincent Indianapolis Hospital
Indianapolis, Indiana, 46260
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
West Michigan Cancer Center
Kalamazoo, Michigan, 49007
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois, 60045
Women's Cancer Center of Nevada
Las Vegas, Nevada, 89106
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095
Norton Hospital Pavilion and Medical Campus
Louisville, Kentucky, 40202
Norton Suburban Hospital and Medical Campus
Louisville, Kentucky, 40207
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Fairview Clinics and Surgery Center Maple Grove
Maple Grove, Minnesota, 55369
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938
Hillcrest Hospital Cancer Center
Mayfield Heights, Ohio, 44124
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407
Marshfield Medical Center - Minocqua
Minocqua, Wisconsin, 54548
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, 60451
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121
Helen F Graham Cancer Center
Newark, Delaware, 19713
Christiana Care Health System-Christiana Hospital
Newark, Delaware, 19718
Norwalk Hospital
Norwalk, Connecticut, 06856
Henry Ford Medical Center-Columbus
Novi, Michigan, 48377
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Nebraska Methodist Hospital
Omaha, Nebraska, 68114
University of Nebraska Medical Center
Omaha, Nebraska, 68198
University of Chicago Medicine-Orland Park
Orland Park, Illinois, 60462
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
Pennsylvania Hospital
Philadelphia, Pennsylvania, 19107
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232
Legacy Good Samaritan Hospital and Medical Center
Portland, Oregon, 97210
Women and Infants Hospital
Providence, Rhode Island, 02905
Beebe Health Campus
Rehoboth Beach, Delaware, 19971
Marshfield Medical Center-Rice Lake
Rice Lake, Wisconsin, 54868
Presbyterian Rust Medical Center/Jorgensen Cancer Center
Rio Rancho, New Mexico, 87124
University of Rochester
Rochester, New York, 14642
Sutter Roseville Medical Center
Roseville, California, 95661
Sutter Medical Center Sacramento
Sacramento, California, 95816
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416
Regions Hospital
Saint Paul, Minnesota, 55101
United Hospital
Saint Paul, Minnesota, 55102
California Pacific Medical Center-Pacific Campus
San Francisco, California, 94115
Sarasota Memorial Hospital
Sarasota, Florida, 34239
Memorial Health University Medical Center
Savannah, Georgia, 31404
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
Savannah, Georgia, 31405
Summit Cancer Care-Candler
Savannah, Georgia, 31405
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
University of Washington Medical Center - Montlake
Seattle, Washington, 98195
Robert Wood Johnson University Hospital Somerset
Somerville, New Jersey, 08876
Mercy Hospital Springfield
Springfield, Missouri, 65804
CoxHealth South Hospital
Springfield, Missouri, 65807
Barnes-Jewish Hospital
St Louis, Missouri, 63110
Washington University School of Medicine
St Louis, Missouri, 63110
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, 54482
Munson Medical Center
Traverse City, Michigan, 49684
Legacy Meridian Park Hospital
Tualatin, Oregon, 97062
Carle Cancer Center
Urbana, Illinois, 61801
The Carle Foundation Hospital
Urbana, Illinois, 61801
Legacy Salmon Creek Hospital
Vancouver, Washington, 98686
Marshfield Clinic-Wausau Center
Wausau, Wisconsin, 54401
Henry Ford West Bloomfield Hospital
West Bloomfield, Michigan, 48322
UHHS-Westlake Medical Center
Westlake, Ohio, 44145
Marshfield Medical Center - Weston
Weston, Wisconsin, 54476
Asplundh Cancer Pavilion
Willow Grove, Pennsylvania, 19090
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Minnesota Oncology Hematology PA-Woodbury
Woodbury, Minnesota, 55125
UMass Memorial Medical Center - Memorial Division
Worcester, Massachusetts, 01605
Midwestern Regional Medical Center
Zion, Illinois, 60099
About this study
Official title: 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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Conditions
- Fallopian Tube Clear Cell Adenocarcinoma, Fallopian Tube Endometrioid Adenocarcinoma, Fallopian Tube High Grade Serous Adenocarcinoma, FIGO Stage III Ovarian Cancer 2014, FIGO Stage IIIA Ovarian Cancer 2014, FIGO Stage IIIA1 Ovarian Cancer
- Being tested
- Carboplatin, Paclitaxel, Ruxolitinib Phosphate, Therapeutic Conventional Surgery
- Medical subject headings
- Fallopian Tube Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarboplatinDrug
Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino
Given IV
PaclitaxelDrug
Also called Anzatax, Asotax, Bristaxol, Praxel
Given IV
Ruxolitinib PhosphateDrug
Also called INCB-18424 Phosphate, Jakafi, Jakavi
Given PO
Therapeutic Conventional SurgeryProcedure or surgery
Undergo TRS
| Study group | Role | What they receive |
|---|---|---|
| Arm I (paclitaxel and carboplatin) | Active comparator | See Detailed Description. Receives: Drug: Carboplatin; Drug: Paclitaxel; Procedure: Therapeutic Conventional Surgery |
| Arm II (ruxolitinib, paclitaxel, and carboplatin) | Experimental | See Detailed Description. Receives: Drug: Carboplatin; Drug: Paclitaxel; Drug: Ruxolitinib Phosphate; Procedure: Therapeutic Conventional Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting Toxicities (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), or delays in treatment caused by toxicities. A DLT is defined as either hematologic or non-hematologic toxicity (assessed in accordance with the CTEP CTCAE Version 4.0), which cause any of the following (any toxicity): a dose delay > 7 days related to any toxicity, an omission of day 8 or day 15 paclitaxel, any treatment related death. For hematologic toxicity: study treatment-related febrile neutropenia, grade 4 neutropenia lasting > 7 days, study treatment-related grade 4 thrombocytopenia or bleeding associated with grade 3 thrombocytopenia. For non-hematologic toxicity: study treatment related grade 3 or grade 4 non-hematologic toxicity.
Measured: 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.
All patients must have measurable disease, and at least one "target lesion" to be used to assess response as defined by 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
Measured: The maximum follow-up time for PFS is 57 months.
Secondary outcomes (7)
Number of Participants With Grade 3 or Higher AE (Phase I and II)
Will be assessed according to CTEP CTCAE version 4.03 (CTCAE version 5.0 will be used starting 04/01/2018). Count of Participants with grade 3 or higher AE. The participants included are the patients in Arm I and the patients in Arm II (DL1 and phase 2). The patients in phase 1 DL2 are not included because they are at a different dose level.
The first 17 patients were entered between 11/14/2016 and 10/19/2017. These are the phase 1 patients. Group in DL1 entered 7 patients between 11/14/2016 - 2/17/2017. The DL2 patients were entered between 4/21/2017 and 10/19/2017. There were 10 entered in DL2 because we had a few (3 patients) who were not evaluable and needed to be replaced. From 6/28/2018 to 2/3/2020, we entered the phase 2 patients (42 vs. 88). The first 7 patients were combined with the active therapy on phase 2, for the toxicity comparison (42 vs. 88+7=95 patients).
Measured: Serious and other adverse events were collected from baseline until 30 days after last treatment, an average of 10 months.
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.
Measured: Up to 6 weeks
Number of Patients Who Discontinue Ruxolitinib in the First 3 Months of Maintenance Therapy Due to Toxicity (Phase I)
Number of patients who discontinue ruxolitinib in the first 3 months of maintenance therapy due to toxicity (Phase I)
Measured: Up to 3 months in the maintenance phase
Progression-free Survival (PFS) (Phase II) (Subset Analysis)
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.
Measured: From study entry to time of progression or death, whichever occurs first, assessed up to 5 years
Number of Patients Who Have Total Gross Resection (Phase II)
The outcome is whether there is a total gross resection rate at time of interval cytoreductive surgery among those who had surgery.
Measured: At the time of surgery (surgery occurred within 6 weeks after completion of cycle 3, as soon as nadir counts permit and surgery deemed safe by investigator)
Number of Participants With Complete Pathological Response (Phase II)
At the time of TRS, complete pathologic response is defined as no evidence of disease on radiographic imaging at the time of radiographic tumor measurement just prior to TRS, no visible or palpable tumor at the time of surgical exploration, and no pathologic evidence of disease in tissue specimens obtained from TRS.
Measured: At the time of tumor reductive surgery or biopsy after 3 cycles (i.e. after 63 days).
Overall Survival (OS) (Phase II)
The effect of treatment on OS will be conducted with a Kaplan-Meier analysis and reported as median survival times.
Measured: The average (median) OS follow-up time is 38 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2016 (estimated)
- Study start14 Nov 2016
- Primary completion30 Sep 2021
- Study completion22 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fallopian Tube Clear Cell AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by NRG OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 147 participants (actual)
Sponsor and investigators
- Lead sponsor
- NRG Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Charles N Landen, Principal investigator, NRG Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02713386
- Sponsor's protocol ID
- NRG-GY007
- Other IDs
- NCI-2016-00203, NRG-GY007, NRG-GY007, NRG-GY007, U10CA180868
- Status last verified
- May 2025
- First submitted
- 15 Mar 2016
- Last updated
- 25 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Landen CN, Buckanovich RJ, Sill MW, Mannel RS, Walker JL, DiSilvestro PA, Mathews CA, Mutch DG, Hernandez ML, Martin LP, Bishop E, Gill SE, Gordinier ME, Burger RA, Aghajanian C, Liu JF, Moore KN, Bookman MA. Phase I and Randomized Phase II Study of Ruxolitinib With Frontline Neoadjuvant Therapy in Advanced Ovarian Cancer: An NRG Oncology Group Study. J Clin Oncol. 2024 Jul 20;42(21):2537-2545. doi: 10.1200/JCO.23.02076. Epub 2024 May 22.
PubMed 38776484