Hepatic Arterial Infusion of Melphalan With Hepatic Perfusion in Treating Patients With Unresectable Liver Cancer

NCT00096083 | Completed Phase 2

• 4 other identifiers: CDR0000391827NCI-04-C-0273NCI-6332DELCATH-G990039
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Hepatic arterial infusion uses a catheter to deliver anticancer substances directly into the liver. Drugs used in chemotherapy, such as melphalan, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving drugs in different ways may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving an hepatic arterial infusion of melphalan together with hepatic perfusion works in treating patients with unresectable liver cancer.

Conditions

Cancer

Keywords

advanced adult primary liver cancer; localized unresectable adult primary liver cancer; recurrent adult primary liver cancer; liver metastases; adenocarcinoma of the colon; adenocarcinoma of the esophagus; adenocarcinoma of the extrahepatic bile duct; adenocarcinoma of the gallbladder; adenocarcinoma of the pancreas; adenocarcinoma of the rectum; adenocarcinoma of the stomach; carcinoma of the appendix; recurrent gallbladder cancer; unresectable gallbladder cancer; recurrent colon cancer; stage IV colon cancer; recurrent esophageal cancer; stage IV esophageal cancer; recurrent extrahepatic bile duct cancer; unresectable extrahepatic bile duct cancer; recurrent gastric cancer; stage IV gastric cancer; recurrent rectal cancer; stage IV rectal cancer; small intestine adenocarcinoma; recurrent small intestine cancer; recurrent islet cell carcinoma; recurrent pheochromocytoma; metastatic pheochromocytoma; pulmonary carcinoid tumor; thyroid gland medullary carcinoma; metastatic gastrointestinal carcinoid tumor; recurrent gastrointestinal carcinoid tumor; recurrent pancreatic cancer; insulinoma; WDHA syndrome; glucagonoma; pancreatic polypeptide tumor; somatostatinoma; stage IV pancreatic cancer; intraocular melanoma; conjunctival melanoma; iris melanoma; recurrent melanoma; stage IV melanoma

Outcome Measures

Primary Outcomes (1)

• To determine the response rate and duration of response to intra-hepatic infusion of melphalan with subsequent venous hemofiltration in patients with primary and metastatic hepatic malignancies

  Survivial

Secondary Outcomes (2)

• To determine the patterns of recurrence following percutaneous hepatic perfusions (PHP) with melphalan

  Survival

• To determine the progression free and overall survival in patients with hepatic malignancies following this therapy

  Survivial

Study Arms (1)

Melphalan Administration PHP

ACTIVE COMPARATOR

Drug: isolated perfusion; Drug: melphalan

Interventions

isolated perfusion DRUG

Melphalan Administration PHP

melphalan DRUG

Melphalan Administration PHP

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed hepatic malignancy * Unresectable disease * Disease predominantly in the parenchyma of the liver * One of the following primary tumor histologies: * Adenocarcinoma of gastrointestinal or other origin * Neuroendocrine tumor (except gastrinoma) * Primary hepatic malignancy (e.g., hepatocellular cancer or intra-hepatic cholangiocarcinoma) * Cutaneous or ocular melanoma (patients must have received prior regional melphalan therapy) * Hepatic metastases from colorectal tumors allowed provided patient has undergone prior first-line chemotherapy, including irinotecan or oxaliplatin * Limited unresectable extrahepatic disease on preoperative radiological studies allowed if life-limiting component of progressive disease is in the liver * Limited extrahepatic disease includes, but is not limited to, the following: * Up to 4 pulmonary nodules each \< 1 cm in diameter * Retroperitoneal lymph nodes each \< 3 cm in diameter * Less than 10 skin or subcutaneous metastases each \< 1 cm in diameter * Asymptomatic bone metastases that have been or could be palliatively treated with external beam radiotherapy * Resectable solitary metastasis to any site * Hormone receptor status: * Not specified PATIENT CHARACTERISTICS: Age * 16 and over Sex * Male or Female Menopausal status * Not specified Performance status * ECOG 0-2 Life expectancy * Not specified Hematopoietic * Platelet count ≥ 75,000/mm\^3 * Hematocrit \> 27% * Absolute neutrophil count ≥ 1,300/mm\^3 Hepatic * Bilirubin ≤ 2.0 mg/dL * PT ≤ 2 seconds of upper limit of normal (ULN) * AST and ALT ≤ 10 times ULN * No Childs class B or C cirrhosis * No portal hypertension by history, endoscopy, or radiologic studies Renal * Creatinine ≤ 1.5 mg/dL OR * Creatinine clearance \> 60 mL/min Cardiovascular * No congestive heart failure * LVEF ≥ 40% Pulmonary * No chronic obstructive pulmonary disease * FEV\_1 ≥ 30% of predicted * DLCO ≥ 40% of predicted Immunologic * No active infection * No severe allergic reaction to iodine contrast agent that is not controlled by premedication with antihistamines or steroids * No known hypersensitivity reaction to melphalan or heparin in the presence of a heparin induced thrombocytopenia (HIT) antibody Other * Weight \> 35 kg * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No documented latex allergy * No evidence of intracranial abnormalities which would lead to risk for bleeding with anticoagulation (e.g., stroke or active metastasis) * No evidence of active ulcer disease PRIOR CONCURRENT THERAPY: Biologic therapy * More than 1 month since prior biologic therapy and recovered Chemotherapy * See Disease Characteristics * More than 1 month since prior chemotherapy and recovered Endocrine therapy * Premenopausal women (i.e., have had a period within the past 12 months) must be willing to undergo hormonal suppression during study treatment Radiotherapy * See Disease Characteristics * More than 1 month since prior radiotherapy and recovered Surgery * No prior Whipple resection Other * Prior intrahepatic perfusion (with or without arterial infusion with floxuridine) or peripheral hepatic perfusion allowed provided the patient had a radiographic partial response of 3 months' duration after therapy * No concurrent immunosuppressive drugs * No concurrent chronic anticoagulation therapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Delcath Systems Inc.: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, 20892-1182, United States

Location

MeSH Terms

Conditions

Neoplasms; Carcinoma, Hepatocellular; Colonic Neoplasms; Adenocarcinoma Of Esophagus; Rectal Neoplasms; Appendiceal Neoplasms; Gallbladder Neoplasms; Esophageal Neoplasms; Bile Duct Neoplasms; Stomach Neoplasms; Carcinoma, Islet Cell; Pheochromocytoma; Carcinoma, Medullary; Pancreatic Neoplasms; Insulinoma; Vipoma; Glucagonoma; Somatostatinoma; Uveal Melanoma; Melanoma

Interventions

Melphalan

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Cecal Neoplasms; Cecal Diseases; Biliary Tract Neoplasms; Biliary Tract Diseases; Gallbladder Diseases; Head and Neck Neoplasms; Esophageal Diseases; Bile Duct Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Paraganglioma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Neuroendocrine; Neoplasms, Ductal, Lobular, and Medullary; Adenoma, Islet Cell; Adenoma; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal Diseases; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Marybeth Hughes, MD

  NCI - Surgery Branch

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2004
• First Posted: November 9, 2004
• Study Start: September 1, 2004
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: October 23, 2013

Record last verified: 2013-10

Locations

US (1)