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)

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

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.

Study Overview

• Status: Terminated
• Conditions: Fallopian Tube Cancer; Recurrent Ovarian Cancer
• Intervention / Treatment: Drug: Cisplatin; Drug: Doxorubicin

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 Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

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

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: Platinol; Platinol-AQ; cis-diamminedichloroplatinum(II) (CDDP); Drug: Doxorubicin; Doxorubicin (25 mg flat dose) prepared in 500 ml dialysis fluid (glucose or icodextrin-based).; Other Names: Adriamycin; hydroxyldaunorubicin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event Rate and/or Laboratory Changes	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.	5 years
Toxicity Rating Based on NCI Common Toxicity Criteria	Patients will be rated for toxicity prior to each cycle using the NCI Common Toxicity Criteria (NCICTC; see the CTCAE, Version 4.0).	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Serum Ca-125 Nadir and/or CT Response (RECIST Criteria)	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.	Up to 5 years (survival)
Kaplan-Meier Curves for Patient Overall Survival	Kaplan-Meier analysis will be done using PROC LIFETEST in Statistical Application Software (SAS).	Up to 5 years, survival

Collaborators and Investigators

• Sponsor: Columbia University
• Investigators: Principal Investigator: Sharyn Lewin, MD, Columbia University

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: July 10, 2012
• First Submitted That Met QC Criteria: August 3, 2012
• First Posted (Estimate): August 8, 2012

Study Record Updates

• Last Update Posted (Actual): March 10, 2017
• Last Update Submitted That Met QC Criteria: January 30, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Primary peritoneal
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Disease Attributes; Adnexal Diseases; Fallopian Tube Diseases; Recurrence; Fallopian Tube Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cisplatin; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: AAAI1246

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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