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A Phase II Study Of Hepatic Arterial Infusion Of Melphalan With Venous Filtration Via Peripheral Hepatic Perfusion (PHP) For Unresectable Primary And Metastatic Cancers Of The Liver

Phase 2
16 Years
Open (Enrolling)

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Trial Information

A Phase II Study Of Hepatic Arterial Infusion Of Melphalan With Venous Filtration Via Peripheral Hepatic Perfusion (PHP) For Unresectable Primary And Metastatic Cancers Of The Liver



- Determine the response rate and duration of response in patients with unresectable
primary or metastatic liver cancer treated with intrahepatic arterial infusion of
melphalan with venous filtration via peripheral hepatic perfusion.


- Determine the patterns of recurrence in patients treated with this regimen.

- Determine progression-free and overall survival of patients treated with this regimen.

- Evaluate the safety and tolerability of this regimen in these patients.

- Assess the filter characteristics including melphalan pharmacokinetics and filtration
of cytokines and clotting factors during and after treatment.

OUTLINE: Patients are stratified according to primary tumor histology (neuroendocrine tumor
vs primary hepatic malignancy vs adenocarcinoma of gastrointestinal or other origin).

Patients undergo peripheral isolated hepatic perfusion in which a catheter is placed via the
groin into the hepatic artery and another into the hepatic vein. Patients then receive
melphalan as an intrahepatic arterial infusion over 15-30 minutes. Treatment repeats
approximately every 3-8 weeks for up to 6 total infusions in the absence of disease
progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 4 months for 1 year, and then
periodically thereafter.

PROJECTED ACCRUAL: A total of 105 patients will be accrued for this study within 4-5 years.

Inclusion Criteria


- 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

- 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



- 16 and over


- Male or Female

Menopausal status

- Not specified

Performance status

- ECOG 0-2

Life expectancy

- Not specified


- Platelet count ≥ 75,000/mm^3

- Hematocrit > 27%

- Absolute neutrophil count ≥ 1,300/mm^3


- 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


- Creatinine ≤ 1.5 mg/dL OR

- Creatinine clearance > 60 mL/min


- No congestive heart failure

- LVEF ≥ 40%


- No chronic obstructive pulmonary disease

- FEV_1 ≥ 30% of predicted

- DLCO ≥ 40% of predicted


- 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


- 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


Biologic therapy

- More than 1 month since prior biologic therapy and recovered


- 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


- See Disease Characteristics

- More than 1 month since prior radiotherapy and recovered


- No prior Whipple resection


- 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

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:


Safety Issue:


Principal Investigator

Marybeth Hughes, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

NCI - Surgery Branch


United States: Food and Drug Administration

Study ID:




Start Date:

September 2004

Completion Date:

August 2014

Related Keywords:

  • Cancer
  • 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
  • Liver Neoplasms



Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office Bethesda, Maryland  20892-1182