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Intraperitoneal Hyperthermic Perfusion With Oxaliplatin in Treating Patients With Stage IV Peritoneal Cancer Due to Appendix Cancer or Colorectal Cancer

Primary Purpose

Carcinoma of the Appendix, Colorectal Cancer, Primary Peritoneal Cavity Cancer

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

oxaliplatin

About this trial

This is an interventional treatment trial for Carcinoma of the Appendix focused on measuring recurrent colon cancer, stage IV colon cancer, carcinoma of the appendix, recurrent rectal cancer, stage IV rectal cancer, primary peritoneal cavity cancer

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed colorectal or appendiceal cancer
- Stage IV disease
- Peritoneal surface dissemination of disease (peritoneal carcinomatosis)
Measurable disease according to RECIST criteria
No active CNS metastases

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Absolute neutrophil count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Creatinine ≤ 1.5 mg/dL OR creatinine clearance > 60 mL/min
Bilirubin ≤ 1.5 mg/dL
Alkaline phosphatase ≤ 3 times upper limit of normal (ULN)
AST and ALT ≤ 3 times ULN
No active infection or fever ≥ 101.3°F within the past 3 days
No other malignancy within the past 5 years except curatively treated basal cell skin cancer, cervical intra-epithelial neoplasia, or localized prostate cancer with a current prostate-specific antigen of < 1.0 mg/dL on 2 successive evaluations, ≥ 3 months apart, with the last evaluation within the past 4 weeks
No peripheral neuropathy ≥ grade 2
No other medical condition, mental illness, or substance abuse that, in the opinion of the principal investigator, would preclude study compliance
No known hypersensitivity to any component of oxaliplatin
No known HIV positivity
No hepatitis B or C positivity (active, previously treated, or both)
Not pregnant or nursing
Negative pregnancy test
Fertile patients and their partners must use effective contraception during and for 90 days after completion of study treatment

PRIOR CONCURRENT THERAPY:

Recovered from prior surgery, radiotherapy, and other anticancer therapies
More than 30 days since prior and no other concurrent investigational therapy
No prior radiotherapy to > 25% of bone marrow
No prior allogeneic stem cell transplantation
No concurrent antiretroviral therapy

Sites / Locations

Wake Forest University Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Hyperthermic Chemoperfusion with Oxaliplatin 200 mg/m2

Hyperthermic Chemoperfusion with Oxaliplatin 250 mg/m2

Arm Description

Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin 200 mg/m2

Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin 250 mg/m2

Outcomes

Primary Outcome Measures

Maximum tolerated dose

Maximum tolerated dose will be determined by the absence of dose limiting toxicites (serious adverse events related to Oxaplatin dosing within 18 days of administration)

Secondary Outcome Measures

Pharmacokinetics

Evaluation of the pharmacokinetics of oxaliplatin in perfusate, normal peritoneum, and peritoneal surface tumors during intraperitoneal hyperthermic chemoperfusion

Change in the phenotypic expression of proteins involved in the apoptotic and heat-stress inducible pathways

Analysis of the expression of proteins involved in the apoptotic and stress-inducible heat shock protein pathways before and after intraperitoneal hyperthermic chemoperfusion with oxaliplatin. These proteins shall include cellular levels of Fas and TRAIL, components of the DISC (FADD, TRADD, FLIP, and Caspase 8), mitochondrial proteins (Bax, Bak, Bcl-2, and Bcl-XL), and the heat shock protein family (HSPs 27, 40, 70, and 90).

Full Information

NCT ID

NCT00458809

First Posted

April 9, 2007

Last Updated

August 7, 2018

Sponsor

Wake Forest University Health Sciences

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00458809

Brief Title

Intraperitoneal Hyperthermic Perfusion With Oxaliplatin in Treating Patients With Stage IV Peritoneal Cancer Due to Appendix Cancer or Colorectal Cancer

Official Title

A Phase I Evaluation of Intraperitoneal Hyperthermic Chemoperfusion With Oxaliplatin for Peritoneal Surface Disemmination of Appendiceal and Colorectal Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

August 2018

Overall Recruitment Status

Completed

Study Start Date

March 2007 (undefined)

Primary Completion Date

November 2007 (Actual)

Study Completion Date

November 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Wake Forest University Health Sciences

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Hyperthermia therapy kills tumor cells by heating them to several degrees above normal body temperature. Adding chemotherapy to hyperthermia and infusing it directly into the abdomen may kill more tumor cells. Giving this treatment after surgery may kill any tumor cells that remain after surgery. PURPOSE: This phase I trial is studying the side effects and best dose of intraperitoneal hyperthermic perfusion with oxaliplatin in treating patients with stage IV peritoneal cancer due to appendix cancer or colorectal cancer.

Detailed Description

OBJECTIVES: Determine the toxicity of intraperitoneal hyperthermic chemoperfusion with oxaliplatin in patients with stage IV peritoneal surface malignancies from primary colorectal or appendiceal cancer. Determine the pharmacokinetics of this drug in perfusate, normal peritoneum, and peritoneal surface tumors in these patients. Evaluate the expression of proteins involved in the apoptotic and stress-inducible heat shock protein pathways (e.g., Fas, TRAIL, DISC components [FADD, TRADD, FLIP, and caspase 8], mitochondrial proteins [Bax, Bak, Bcl-2, Bcl-X_L], and heat shock proteins [HSPs 27, 40, 70 and 90]) before and after drug therapy. OUTLINE: This is a nonrandomized, open-label, dose-escalation study. Patients undergo gross tumor resection on day 1. After tumor debulking, patients receive oxaliplatin over 2 hours by intraperitoneal hyperthermic chemotherapy (IPHC). Cohorts of 3-6 patients in each stratum receive escalating doses of oxaliplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD. Patients undergo blood and tissue sampling before and after IPHC for pharmacokinetic studies and for evaluation of proteins involved in apoptosis and heat-shock-mediated cell death (e.g., Fas, TRAIL, FADD, TRADD, FLIP, caspase 8, Bax, Bak, Bcl-X, and heat shock proteins 27, 40, 70, and 90). After completion of study treatment, patients are followed periodically for at least 1 year. PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Carcinoma of the Appendix, Colorectal Cancer, Primary Peritoneal Cavity Cancer

Keywords

recurrent colon cancer, stage IV colon cancer, carcinoma of the appendix, recurrent rectal cancer, stage IV rectal cancer, primary peritoneal cavity cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

16 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Hyperthermic Chemoperfusion with Oxaliplatin 200 mg/m2

Arm Type

Experimental

Arm Description

Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin 200 mg/m2

Arm Title

Hyperthermic Chemoperfusion with Oxaliplatin 250 mg/m2

Arm Type

Experimental

Arm Description

Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin 250 mg/m2

Intervention Type

Drug

Intervention Name(s)

oxaliplatin

Intervention Description

Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin

Primary Outcome Measure Information:

Title

Maximum tolerated dose

Description

Maximum tolerated dose will be determined by the absence of dose limiting toxicites (serious adverse events related to Oxaplatin dosing within 18 days of administration)

Time Frame

18 days

Secondary Outcome Measure Information:

Title

Pharmacokinetics

Description

Evaluation of the pharmacokinetics of oxaliplatin in perfusate, normal peritoneum, and peritoneal surface tumors during intraperitoneal hyperthermic chemoperfusion

Time Frame

day of surgery (day one)

Title

Change in the phenotypic expression of proteins involved in the apoptotic and heat-stress inducible pathways

Description

Time Frame

Day of surgery (day one)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

Eligibility Criteria

DISEASE CHARACTERISTICS: Histologically or cytologically confirmed colorectal or appendiceal cancer Stage IV disease Peritoneal surface dissemination of disease (peritoneal carcinomatosis) Measurable disease according to RECIST criteria No active CNS metastases PATIENT CHARACTERISTICS: ECOG performance status 0-2 Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Creatinine ≤ 1.5 mg/dL OR creatinine clearance > 60 mL/min Bilirubin ≤ 1.5 mg/dL Alkaline phosphatase ≤ 3 times upper limit of normal (ULN) AST and ALT ≤ 3 times ULN No active infection or fever ≥ 101.3°F within the past 3 days No other malignancy within the past 5 years except curatively treated basal cell skin cancer, cervical intra-epithelial neoplasia, or localized prostate cancer with a current prostate-specific antigen of < 1.0 mg/dL on 2 successive evaluations, ≥ 3 months apart, with the last evaluation within the past 4 weeks No peripheral neuropathy ≥ grade 2 No other medical condition, mental illness, or substance abuse that, in the opinion of the principal investigator, would preclude study compliance No known hypersensitivity to any component of oxaliplatin No known HIV positivity No hepatitis B or C positivity (active, previously treated, or both) Not pregnant or nursing Negative pregnancy test Fertile patients and their partners must use effective contraception during and for 90 days after completion of study treatment PRIOR CONCURRENT THERAPY: Recovered from prior surgery, radiotherapy, and other anticancer therapies More than 30 days since prior and no other concurrent investigational therapy No prior radiotherapy to > 25% of bone marrow No prior allogeneic stem cell transplantation No concurrent antiretroviral therapy

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John H. Stewart, MD

Organizational Affiliation

Wake Forest University Health Sciences

Official's Role

Study Chair

Facility Information:

Facility Name

Wake Forest University Comprehensive Cancer Center

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27157-1096

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

18493824

Citation

Stewart JH 4th, Shen P, Russell G, Fenstermaker J, McWilliams L, Coldrun FM, Levine KE, Jones BT, Levine EA. A phase I trial of oxaliplatin for intraperitoneal hyperthermic chemoperfusion for the treatment of peritoneal surface dissemination from colorectal and appendiceal cancers. Ann Surg Oncol. 2008 Aug;15(8):2137-45. doi: 10.1245/s10434-008-9967-1. Epub 2008 May 21. Erratum In: Ann Surg Oncol. 2012 Jul;19(7):2421.

Results Reference

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Intraperitoneal Hyperthermic Perfusion With Oxaliplatin in Treating Patients With Stage IV Peritoneal Cancer Due to Appendix Cancer or Colorectal Cancer

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