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

Ovarian Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01767675
• Other study ID #: 12-275
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 8, 2013
• Est. completion date: January 2025

Study information

• Verified date: February 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 99
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

Inclusion Criteria for Eligibility Prior to Surgery:

• 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 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 = 1.5mg/dl
• 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 oral anti-coagulation (such as warfarin or rivaroxaban), 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.

Inclusion Criteria for Eligibility Post-Surgery:

• Patients will be consented prior to the surgical evaluation/cytoreductive surgery. Patients must have less than or equal to 0.5cm residual disease at the completion of the secondary surgery to be eligible for the study. Exclusion Criteria:

Exclusion Criteria for Eligibility Prior to Surgery:

• 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 1 year 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.
• History of cerebrovascular disease.
• Immune deficiency: Clinically significant primary or acquired immune deficiency (i.e. AIDS or on immunosuppressive medication after organ transplant).
• 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 with known carboplatin or cisplatin allergy.
• Life expectancy < 12 weeks.

Exclusion Criteria for Eligibility Post-Surgery:

• Evidence of extensive intraperitoneal adhesions at the time of surgery, as determined by the operating surgeon which prohibits intraperitoneal therapy.

Related Conditions & MeSH terms

• Fallopian Tube Neoplasms
• Fallopian Tubes Cancer
• Fever
• Hyperthermia
• Ovarian Cancer
• Peritoneal Cancer
• Peritoneal Neoplasms

Intervention

Procedure:
• Secondary Cytoreductive Surgery

Drug:
• Carboplatin Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

• platinum-based systemic chemotherapy postoperatively
5 cycles
• platinum-based systemic chemotherapy postoperatively
6 cycles

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Hartford Healthcare Cancer Institute @ Hartford Hospital	Hartford	Connecticut
United States	Baptist Health South Florida	Miami	Florida
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	Memorial Sloan Kettering Nassau (All protocol activities, except surgery)	Uniondale	New York

Sponsors (6)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Baptist Health South Florida, Hartford HealthCare, Mayo Clinic, University of Chicago, University of Pittsburgh

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	determine the proportion of patients who are without evidence of disease progression	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.	24 months
Secondary	To determine the toxicity and postoperative complications rate	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. and MSKCC Surgical Secondary Events Grading System for complications.	4 weeks post op
Secondary	determine the completion rate of four cycles	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.	5 years
Secondary	pharmacokinetics	in a subset of patients randomized to receive HIPEC in the OR. In patients randomized to HIPEC, peritoneal fluid and blood samples only from MSKCC patients will be drawn before, during and after the HIPEC procedure.	5 years

External Links

•   Memorial Sloan Kettering Cancer Center