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| ID | Type | Description | Link |
|---|---|---|---|
| P30CA012197 | U.S. NIH Grant/Contract | View source | |
| CCCWFU-59106 | |||
| CCCWFU-IRB00000847 | |||
| CCCWFU-59106 IPHC |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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.
OBJECTIVES:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Hyperthermic Chemoperfusion with Oxaliplatin 200 mg/m2 | Experimental | Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin 200 mg/m2 |
|
| Hyperthermic Chemoperfusion with Oxaliplatin 250 mg/m2 | Experimental | Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin 250 mg/m2 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| oxaliplatin | Drug | Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) | 18 days |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics | Evaluation of the pharmacokinetics of oxaliplatin in perfusate, normal peritoneum, and peritoneal surface tumors during intraperitoneal hyperthermic chemoperfusion | day of surgery (day one) |
| Change in the phenotypic expression of proteins involved in the apoptotic and heat-stress inducible pathways |
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DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed colorectal or appendiceal cancer
Measurable disease according to RECIST criteria
No active CNS metastases
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
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| Name | Affiliation | Role |
|---|---|---|
| John H. Stewart, MD | Wake Forest University Health Sciences | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Wake Forest University Comprehensive Cancer Center | Winston-Salem | North Carolina | 27157-1096 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18493824 | Result | 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. |
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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). |
| Day of surgery (day one) |
| ID | Term |
|---|---|
| D001063 | Appendiceal Neoplasms |
| D015179 | Colorectal Neoplasms |
| D003110 | Colonic Neoplasms |
| D012004 | Rectal Neoplasms |
| ID | Term |
|---|---|
| D002430 | Cecal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D002429 | Cecal Diseases |
| D007410 | Intestinal Diseases |
| D003108 | Colonic Diseases |
| D012002 | Rectal Diseases |
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| ID | Term |
|---|---|
| D000077150 | Oxaliplatin |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
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