A Phase II Combined Modality Protocol of Debulking Surgery With HIPEC Followed by Intraperitoneal Chemotherapy for the Treatment of Recurrent Ovarian, Primary Peritoneal & Fallopian Tube Cancers (HIPEC)

• ClinicalTrials.gov Identifier: NCT01659554
• Recruitment Status: Terminated
• First Posted: August 8, 2012
• Results First Posted: March 3, 2015
• Last Update Posted: March 10, 2017
• Sponsor: Columbia University
• Information provided by (Responsible Party): Columbia University

Study Description

Brief Summary:

The primary objective of this study is to investigate the feasibility, tolerability and safety of surgical debulking and resection with heated intraoperative chemotherapy (HIPEC) followed by repeated intraperitoneal chemotherapy for treatment of recurrent ovarian, primary peritoneal, and fallopian tube carcinomas.

Condition or disease	Intervention/treatment	Phase
Recurrent Ovarian Cancer; Fallopian Tube Cancer	Drug: Cisplatin; Drug: Doxorubicin	Phase 2

Detailed Description:

This is a phase II , open label, single center study of surgery followed by heated intraoperative cisplatin in patients with recurrent ovarian, primary peritoneal or fallopian tube cancers. Approximately twenty patients will receive surgery and intraoperative (hyperthermic) cisplatin followed by four consecutive courses of outpatient intraperitoneal cisplatin and doxorubicin given on days 1 and 8 during a 3 week cycle.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Combined Modality Protocol of Debulking Surgery With Heated Intraoperative Chemotherapy (HIPEC) Followed by Intraperitoneal Chemotherapy for the Treatment of Recurrent Ovarian, Primary Peritoneal and Fallopian Tube Cancers
• Study Start Date: March 2012
• Actual Primary Completion Date: April 2014
• Actual Study Completion Date: April 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Out-Patient Intraperitoneal Chemotherapy; Intraoperative (hyperthermic) cisplatin followed by 4 courses of intraperitoneal cisplatin and doxorubicin given on days 1 & 8 during a 3 week cycle.	Drug: Cisplatin; Cisplatin (75 mg/m2) prepared in 2L normal saline.; Other Names: cis-diamminedichloroplatinum(II) (CDDP); Platinol; Platinol-AQ; Drug: Doxorubicin; Doxorubicin (25 mg flat dose) prepared in 500 ml dialysis fluid (glucose or icodextrin-based).; Other Names: hydroxyldaunorubicin; Adriamycin

Outcome Measures

Primary Outcome Measures :

1. Adverse Event Rate and/or Laboratory Changes [ Time Frame: 5 years ]
   The adverse event rate and laboratory changes will be used to investigate the safety of surgical debulking with heated intraperitoneal chemotherapy (HIPEC) combined with repeated intraperitoneal chemotherapy.
2. Toxicity Rating Based on NCI Common Toxicity Criteria [ Time Frame: Up to 5 years ]
   Patients will be rated for toxicity prior to each cycle using the NCI Common Toxicity Criteria (NCICTC; see the CTCAE, Version 4.0).

Secondary Outcome Measures :

1. Time to Serum Ca-125 Nadir and/or CT Response (RECIST Criteria) [ Time Frame: Up to 5 years (survival) ]
   Efficacy of surgical resection with HIPEC combined with repeated intraperitoneal chemotherapy: The end point will be the objective response rate and progression-free survival as well as the overall survival, if feasible. We will analyze the time to serum Ca 125 nadir and/or CT response based on Recist criteria.
2. Kaplan-Meier Curves for Patient Overall Survival [ Time Frame: Up to 5 years, survival ]
   Kaplan-Meier analysis will be done using PROC LIFETEST in Statistical Application Software (SAS).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patients must have histologically confirmed ovarian, primary peritoneal or fallopian tube carcinoma.
2. Patients must have measurable evidence of recurrent intraabdominal disease based on Computed tomography (CT scan) findings.

3. Patients must fulfill the following with regard to prior chemotherapy:

   1. 4 weeks or greater since conclusion of prior chemotherapy;
   2. Prior intraperitoneal chemotherapy with cisplatin is acceptable; and,
   3. Prior systemic chemotherapy is acceptable.
4. Patients must have a Karnofsky Performance Status of > 70%
5. Patients must have an estimated life expectancy of at least 16 weeks.
6. Patient assurance of study compliance and geographic proximity that allows for adequate follow-up.

7. Patients must have adequate organ function at the screening visit as defined by the following laboratory values:

   Absolute neutrophil count (ANC) ≥1.5 x 109/L Platelet count ≥100 x 109/L Hemoglobin ≥8 g/dL Albumin ≥ 2 g/dL Total Bilirubin ≤ 2.5 x ULN* Alkaline phosphatase ≤ 3.0 x ULN* Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN Creatinine ≤ 1.5 x ULN

8. Patient must have signed informed consent
9. Patient must be at least 18 years of age
10. Following cytoreductive surgery, patient's residual disease should be no larger than 1cm to Receive HIPEC and continue with normothermic IP chemotherapy

Exclusion criteria:

1. Have active peripheral neuropathy of Grade 2 or greater intensity, as defined by the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE; Version 4).
2. Have experienced myocardial infarction within 6 months prior to enrollment or have New York Hospital Association (NYHA) Class III or IV heart failure (see section 16.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
3. Prior radiation therapy within 4 weeks of enrollment.
4. Have uncontrolled active systemic infection requiring therapy.
5. Have a history of allergic reaction attributable to compounds containing boron or mannitol or hypersensitivity reactions to drugs formulated with polysorbate 80.
6. Have had a serious concomitant systemic disorders (including oncologic emergencies) incompatible with the study (at the discretion of the investigator).
7. Have had a "currently active" second malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix are not to be registered. Patients who are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse.
8. Have had any investigational agent within 4 weeks before enrollment into the study.
9. Have a history of a serious medical or psychiatric illness preventing informed consent or, in the opinion of the investigator, would make the patient a poor study candidate.
10. Evidence of extraabdominal metastasis on preinclusion thoracic computed tomography (CT) scans (i.e. brain or chest disease).

Contacts and Locations

Locations

United States, New York

Columbia University Medical Center

New York, New York, United States, 10032

Sponsors and Collaborators

Columbia University

Investigators

• Principal Investigator: Sharyn Lewin, MD; Columbia University

More Information

• Responsible Party: Columbia University
• ClinicalTrials.gov Identifier: NCT01659554
• Other Study ID Numbers: AAAI1246
• First Posted: August 8, 2012
• Results First Posted: March 3, 2015
• Last Update Posted: March 10, 2017
• Last Verified: January 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Columbia University:

Primary peritoneal

Additional relevant MeSH terms:

Fallopian Tube Neoplasms; Neoplasms by Site; Neoplasms; Adnexal Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Fallopian Tube Diseases; Cisplatin; Doxorubicin; Liposomal doxorubicin; Antineoplastic Agents; Antibiotics, Antineoplastic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action