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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
Sponsored by
Wake Forest University Health Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

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

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

First Posted
April 9, 2007
Last Updated
August 7, 2018
Sponsor
Wake Forest University Health Sciences
Collaborators
National Cancer Institute (NCI)
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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
No
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
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).
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
No
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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