Outcomes After Secondary Cytoreductive Surgery With or Without Carboplatin Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Followed by Systemic Combination Chemotherapy for Recurrent Platinum-Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01767675
First received: January 10, 2013
Last updated: July 2, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to see if the investigators can improve the treatment of this type of cancer. They want to find out what effects, good and/or bad, giving heated chemotherapy into the belly, known as hyperthermic intraperitoneal chemotherapy (HIPEC), has on the patient and this type of cancer.

The goal of HIPEC is to expose any cancer left in the abdomen after surgery to high doses of chemotherapy. The chemotherapy is heated in the hope that this will make it easier for it to get into and kill the cancer cells. The drug used for HIPEC will be carboplatin, a Food and Drug Administration (FDA) approved drug for use in ovarian, fallopian tube or primary peritoneal cancer.


Condition Intervention Phase
Ovarian Cancer
Fallopian Tubes Cancer
Peritoneal Cancer
Procedure: Secondary Cytoreductive Surgery
Drug: Carboplatin Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
Drug: platinum-based systemic chemotherapy postoperatively
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Randomized Study: Outcomes After Secondary Cytoreductive Surgery With or Without Carboplatin Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Followed by Systemic Combination Chemotherapy for Recurrent Platinum-Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • determine the proportion of patients who are without evidence of disease progression [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    A proportion of patients > 40%, who are without evidence of disease progression at 24 months, is considered acceptable, whereas a proportion of < 25% is considered not acceptable in this patient population.


Secondary Outcome Measures:
  • To determine the toxicity and postoperative complications rate [ Time Frame: 4 weeks post op ] [ Designated as safety issue: Yes ]
    The safety endpoint of our trial is to determine toxicity and postoperative complication rates in both arms using NCI Common Terminology Criteria for Adverse Events version 4.0.

  • determine the completion rate of four cycles [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    A secondary analysis of estimating the completion rate will be conducted. The completion rate and a 95% confidence interval will be calculated for each arm separately. Completion is defined as patients being able to complete >4 out of 5 or 6 cycles of a standard systemic chemotherapy.

  • pharmacokinetics [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    in a subset of patients randomized to receive HIPEC in the OR. In patients randomized to HIPEC, peritoneal fluid and blood samples will be drawn before, during and after the HIPEC procedure.


Estimated Enrollment: 98
Study Start Date: January 2013
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Secondary Cytoreductive Surgery with HIPEC
secondary cytoreductive surgery (CRS) with or without carboplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) followed by systemic combination chemotherapy for recurrent platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer. Patients will be randomized intraoperatively to undergo CRS with HIPEC (arm A) or CRS only (arm B) in a manner 1:1. Both arms will receive a standard platinum-based systemic chemotherapy postoperatively (5 cycles in arm A and 6 cycles in arm B). In patients randomized to HIPEC, peritoneal fluid and blood samples will be drawn before, during and after the HIPEC procedure.
Procedure: Secondary Cytoreductive Surgery Drug: Carboplatin Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Drug: platinum-based systemic chemotherapy postoperatively
5 cycles
Experimental: Secondary Cytoreductive Surgery without HIPEC
secondary cytoreductive surgery (CRS) with or without carboplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) followed by systemic combination chemotherapy for recurrent platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer. Patients will be randomized intraoperatively to undergo CRS with HIPEC (arm A) or CRS only (arm B) in a manner 1:1. Both arms will receive a standard platinum-based systemic chemotherapy postoperatively (5 cycles in arm A and 6 cycles in arm B).
Procedure: Secondary Cytoreductive Surgery Drug: platinum-based systemic chemotherapy postoperatively
6 cycles

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age > 21 years old.
  • Patients with histologic diagnosis of epithelial ovarian carcinoma, primary peritoneal carcinoma, or fallopian tube carcinoma that has recurred >6 months since platinum-based chemotherapy (first recurrence) and who are scheduled for secondary surgical evaluation/cytoreduction.
  • Histologic epithelial cell types include serous, endometrioid, clear cell, or undifferentiated carcinomas, transitional cell carcinoma, mixed epithelial carcinoma, malignant Brenner's tumor, or adenocarcinoma N.O.S.
  • Karnofsky Performance Status (KPS) of ≥ 70%.
  • Disease-free interval < 30 months.
  • No prior chemotherapy in the recurrent setting. Prior hormonal therapy is permitted. Concomitant anti-neoplastic anti-hormonal therapy (including tamoxifen, aromatase inhibitors etc.) is not allowed for patients participating in study treatment. Low-dose (physiologic) estrogen hormone-replacement therapy (HRT) may be given.
  • Patients receiving maintenance biologic therapy are eligible, provided their recurrence is documented more than 6 months from completion of primary cytotoxic chemotherapy (includes maintenance chemotherapy) and a minimum of 3 weeks has elapsed since their last infusion of biologic therapy at the start of protocol intervention, day 1.
  • Patients will be consented prior to the surgical evaluation/cytoreductive surgery.
  • Patients must have less than or equal to 0.5 cm residual disease at the completion of the secondary surgery to be eligible for the study.
  • Patients must be, after evaluation by the investigator, appropriate candidates for the administration of 5 to 6 cycles of standard platinum-based combination chemotherapy (carboplatin and paclitaxel, carboplatin and liposomal doxorubicin, or carboplatin and gemcitabine) following CRS with or without HIPEC.
  • Bone marrow function:
  • Hemoglobin ≥ 8.5 g/dL.
  • Absolute neutrophil count (ANC) ≥ 1,000/mm3.
  • Platelets ≥ 100,000/mm3.
  • Renal function:
  • Creatinine ≤ 1.5 times the upper limit of normal (ULN) or calculated creatinine clearance ≥ 60ml/min.
  • Hepatic function:
  • Bilirubin ≤ 1.5 times ULN.
  • ALT ≤ 3 times the ULN.
  • AST ≤ 3 times the ULN.
  • Neurologic function:

Peripheral neuropathy ≤ CTC AE grade 2.

  • Blood coagulation parameters:
  • PT with an INR of ≤ 1.5 and a PTT ≤ 1.5 times the ULN. For patients on full-dose warfarin, in-range INR (usually between 2 and 3) and a PTT <1.2 times the ULN.
  • Patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to CRS and must be practicing an effective form of contraception during the study period.

Exclusion Criteria:

  • Tumors of low malignant potential (borderline carcinomas).
  • Subjects who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded.
  • Patients with a history of primary endometrial cancer are excluded unless the following conditions are met:
  • Stage not greater than IA.
  • Not a poorly differentiated subtype (including papillary serous, clear cell or other FIGO grade 3 lesions)
  • With the exception of non-melanoma skin cancer and other specific malignancies as noted above, subjects with other invasive malignancies, who had any evidence of the other cancer present within the last 3 years or whose previous cancer treatment contraindicates this protocol therapy, are excluded.
  • Subjects with known active acute hepatitis.
  • Subjects with active infection that requires parenteral antibiotics.
  • Active coronary artery disease (defined as unstable angina or a positive cardiac stress test).
  • Patients with a history of coronary artery disease may be included if they have had a normal stress test within 30 days of enrollment.
  • Uncontrolled hypertension defined as > 140/90 and not cleared for surgery at the time of consent..
  • New York Heart Association (NYHA) Class II or higher Congestive heart failure.
  • Renal insufficiency with serum creatinine level ≥ 1.5 times the upper limit of normal or calculated creatinine clearance < 60 ml/min.
  • History of cerebrovascular disease.
  • Immune deficiency.
  • Patients with other concurrent severe medical problems unrelated to the malignancy that would significantly limit full compliance with the study or places them at an unacceptable risk for participation in the study.
  • Patients under the age of 21. This protocol does not include children because the number of children with these types of cancer is limited, and because the majority is already part of a nationwide pediatric cancer research network.
  • Patients with known carboplatin or cisplatin allergy.
  • Evidence of extensive intraperitoneal adhesions at the time of surgery, as determined by the operating surgeon which prohibits intraperitoneal therapy.
  • Life expectancy < 12 weeks.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01767675

Contacts
Contact: Dennis Chi, MD 212-639-5016
Contact: Roisin O'Cearbhaill, MB BCh 646-888-4227

Locations
United States, New Jersey
Memoral Sloan Kettering Cancer Center Recruiting
Basking Ridge, New Jersey, United States
Contact: Dennis Chi, MD    212-639-5016      
United States, New York
Memorial Sloan-Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Dennis Chi, MD    212-639-5016      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Dennis Chi, MD    212-639-5016      
Contact: Roisin O'Cearbhaill, MB BCh    646-888-4227      
Principal Investigator: Dennis Chi, MD         
Memorial Sloan-Kettering at Mercy Medical Center Recruiting
Rockville Centre, New York, United States
Contact: Dennis Chi, MD    212-639-5016      
Memorial Sloan-Kettering Cancer Center at Mercy Medical Center Recruiting
Rockville Centre, New York, United States, 11570
Contact: Dennis Chi, MD    212-639-5016      
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: Dennis Chi, MD    212-639-5016      
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Dennis Chi, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01767675     History of Changes
Other Study ID Numbers: 12-275
Study First Received: January 10, 2013
Last Updated: July 2, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
Secondary Cytoreductive Surgery
Carboplatin
Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
12-175

Additional relevant MeSH terms:
Fever
Ovarian Neoplasms
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Body Temperature Changes
Signs and Symptoms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Fallopian Tube Diseases
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014