Ruxolitinib Phosphate, Paclitaxel, and Carboplatin in Treating Patients With Stage III-IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
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|ClinicalTrials.gov Identifier: NCT02713386|
Recruitment Status : Active, not recruiting
First Posted : March 18, 2016
Last Update Posted : June 2, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Fallopian Tube Clear Cell Adenocarcinoma Fallopian Tube Endometrioid Adenocarcinoma Fallopian Tube High Grade Serous 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 Ovarian Clear Cell Adenocarcinoma Ovarian Endometrioid Adenocarcinoma Ovarian High Grade Serous Adenocarcinoma Primary Peritoneal Endometrioid Adenocarcinoma Primary Peritoneal High Grade Serous 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||Drug: Carboplatin Drug: Paclitaxel Drug: Ruxolitinib Phosphate Procedure: Therapeutic Conventional Surgery||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||147 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||November 14, 2016|
|Actual Primary Completion Date :||September 30, 2021|
|Estimated Study Completion Date :||September 30, 2022|
Active Comparator: Arm I (paclitaxel and carboplatin)
See Detailed Description.
Procedure: Therapeutic Conventional Surgery
Experimental: Arm II (ruxolitinib, paclitaxel, and carboplatin)
See Detailed Description.
Drug: Ruxolitinib Phosphate
Procedure: Therapeutic Conventional Surgery
- Incidence of hematologic (heme) dose-limiting toxicity (Phase I) [ Time Frame: 42 days (2 cycles) ]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).
- Progression-free survival (PFS) (Phase II) [ Time Frame: From study entry to time of progression or death, whichever occurs first, assessed up to 5 years ]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.
- Incidence of adverse events (Phase I) [ Time Frame: Up to 5 years ]Will be assessed according to CTEP CTCAE version 4.03 (CTCAE version 5.0 will be used starting 04/01/2018).
- 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) [ Time Frame: Up to 6 weeks ]Frequencies will be given by the dose-level administered.
- Number of patients who discontinue ruxolitinib in the first 3 months of maintenance therapy due to toxicity (Phase I) [ Time Frame: Up to 3 months in the maintenance phase ]
- Progression-free survival (PFS) (Phase II) [ Time Frame: From study entry to time of progression or death, whichever occurs first, assessed up to 5 years ]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.
- Proportion of patients who have total gross resection (Phase II) [ Time Frame: At the time of surgery ]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.
- Complete pathological response (Phase II) [ Time Frame: Up to 5 years ]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.
- Overall survival (OS) (Phase II) [ Time Frame: From randomization until death or date last seen, assessed up to 5 years ]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.
- Change in cancer stem cells (CSC) observed in tissue [ Time Frame: Baseline up to 63 days (3 cycles) ]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.
- Change in serum C-reactive protein (CRP) [ Time Frame: Baseline up to 63 days (3 cycles) ]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.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||Female|
|Accepts Healthy Volunteers:||No|
- 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)
- 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)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02713386
|Principal Investigator:||Charles N Landen||NRG Oncology|
|Responsible Party:||NRG Oncology|
|Other Study ID Numbers:||
NCI-2016-00203 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-GY007 ( Other Identifier: NRG Oncology )
NRG-GY007 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
|First Posted:||March 18, 2016 Key Record Dates|
|Last Update Posted:||June 2, 2022|
|Last Verified:||June 2022|
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Adenocarcinoma, Clear Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Neoplasms by Site
Genital Diseases, Female
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Genital Neoplasms, Female
Endocrine System Diseases
Fallopian Tube Diseases
Digestive System Neoplasms
Digestive System Diseases