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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

Primary Purpose

Ovarian Cancer, Fallopian Tubes Cancer, Peritoneal Cancer

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Secondary Cytoreductive Surgery
Carboplatin Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
platinum-based systemic chemotherapy postoperatively
platinum-based systemic chemotherapy postoperatively
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Cancer focused on measuring Secondary Cytoreductive Surgery, Carboplatin, Hyperthermic Intraperitoneal Chemotherapy (HIPEC), 12-275

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Hartford Healthcare Cancer Institute @ Hartford Hospital
  • Baptist Health South Florida
  • University of Chicago Medical Center
  • Mayo Clinic
  • Memorial Sloan Kettering Basking Ridge
  • Memorial Sloan Kettering Monmouth
  • Memorial Sloan Kettering Bergen
  • Memorial Sloan Kettering Commack
  • Memorial Sloan Kettering Westchester
  • Memorial Sloan Kettering Cancer Center
  • Memorial Sloan Kettering Nassau (All protocol activities, except surgery)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Secondary Cytoreductive Surgery with HIPEC

Secondary Cytoreductive Surgery without HIPEC

Arm Description

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 some patients randomized to HIPEC at MSKCC only , peritoneal fluid and blood samples will be drawn before, during and after the HIPEC procedure.

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
January 10, 2013
Last Updated
July 6, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Mayo Clinic, Baptist Health South Florida, Hartford HealthCare, University of Pittsburgh, University of Chicago
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1. Study Identification

Unique Protocol Identification Number
NCT01767675
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 8, 2013 (undefined)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
January 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Mayo Clinic, Baptist Health South Florida, Hartford HealthCare, University of Pittsburgh, University of Chicago

4. Oversight

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer, Fallopian Tubes Cancer, Peritoneal Cancer
Keywords
Secondary Cytoreductive Surgery, Carboplatin, Hyperthermic Intraperitoneal Chemotherapy (HIPEC), 12-275

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
99 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Secondary Cytoreductive Surgery with HIPEC
Arm Type
Experimental
Arm Description
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 some patients randomized to HIPEC at MSKCC only , peritoneal fluid and blood samples will be drawn before, during and after the HIPEC procedure.
Arm Title
Secondary Cytoreductive Surgery without HIPEC
Arm Type
Experimental
Arm Description
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).
Intervention Type
Procedure
Intervention Name(s)
Secondary Cytoreductive Surgery
Intervention Type
Drug
Intervention Name(s)
Carboplatin Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
Intervention Type
Drug
Intervention Name(s)
platinum-based systemic chemotherapy postoperatively
Intervention Description
5 cycles
Intervention Type
Drug
Intervention Name(s)
platinum-based systemic chemotherapy postoperatively
Intervention Description
6 cycles
Primary Outcome Measure Information:
Title
determine the proportion of patients who are without evidence of disease progression
Description
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.
Time Frame
24 months
Secondary Outcome Measure Information:
Title
To determine the toxicity and postoperative complications rate
Description
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.
Time Frame
4 weeks post op
Title
determine the completion rate of four cycles
Description
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.
Time Frame
5 years
Title
pharmacokinetics
Description
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.
Time Frame
5 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dennis Chi, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hartford Healthcare Cancer Institute @ Hartford Hospital
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06102
Country
United States
Facility Name
Baptist Health South Florida
City
Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Memorial Sloan Kettering Basking Ridge
City
Basking Ridge
State/Province
New Jersey
Country
United States
Facility Name
Memorial Sloan Kettering Monmouth
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Facility Name
Memorial Sloan Kettering Bergen
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Facility Name
Memorial Sloan Kettering Commack
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Facility Name
Memorial Sloan Kettering Westchester
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Memorial Sloan Kettering Nassau (All protocol activities, except surgery)
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
34019431
Citation
Zivanovic O, Chi DS, Zhou Q, Iasonos A, Konner JA, Makker V, Grisham RN, Brown AK, Nerenstone S, Diaz JP, Schroeder ED, Langstraat CL, Paroder V, Lakhman Y, Soldan K, Su K, Gardner GJ, Andikyan V, Guo J, Jewell EL, Long Roche K, Troso-Sandoval T, Lichtman SM, Moukarzel LA, Dessources K, Abu-Rustum NR, Aghajanian C, Tew WP, Beumer J, Sonoda Y, O'Cearbhaill RE. Secondary Cytoreduction and Carboplatin Hyperthermic Intraperitoneal Chemotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: An MSK Team Ovary Phase II Study. J Clin Oncol. 2021 Aug 10;39(23):2594-2604. doi: 10.1200/JCO.21.00605. Epub 2021 May 21.
Results Reference
derived
Links:
URL
http://www.mskcc.org/
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

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

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