Cyclophosphamide, Radiation Therapy, and Poly ICLC in Treating Patients With Unresectable, Recurrent, Primary, or Metastatic Liver Cancer

January 11, 2014 updated by: Andrew de la Torre, Rutgers, The State University of New Jersey

Phase I/II Study of Autologous Tumor Cell Vaccination Using Metronomic Cyclophosphamide, 3-Dimensional Conformal Radiotherapy, Intra/Peri-Tumor Injection of Poly ICLC With Trans-Hepatic Arterial Embolization Followed by Poly ICLC Boosting in Patients With Unresectable, Recurrent, or Metastatic Cancers in the Liver (Hepatoma, Cholangiocarcinoma, Neuroendocrine, Breast, Colon, Gastric, and Esophageal Cancer)

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Poly ICLC may stop the growth of liver cancer by blocking blood flow to the tumor. Giving the drug directly into the arteries around the tumor may kill more tumor cells. Giving cyclophosphamide and radiation therapy together with poly ICLC may be an effective treatment for liver cancer.

PURPOSE: This phase I/II trial is studying the side effects of giving cyclophosphamide, radiation therapy, and poly ICLC together and to see how well they work in treating patients with unresectable, recurrent, primary, or metastatic liver cancer.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • To study the safety and effectiveness of a strategy to establish robust anticancer immunologic body defenses by using low-dose radiation therapy to the liver cancer in order to increase tumor targetability; inject a body defense activator, polyinosinic-polycytidylic acid polylysine carboxymethylcellulose (poly ICLC, hiltonol, oncovir), into and around the cancer to activate sentinel dendritic cells to alarm body defenses; and shut down local production of factors that suppress the body's natural anticancer defenses by starving the cancer of its blood supply within the liver.

OUTLINE: Patients receive low-dose oral cyclophosphamide once daily on days 1-21 and undergo 3-dimensional conformal radiotherapy on days 21-23. On day 24, patients undergo an intra- or peri-tumoral polyinosinic-polycytidylic acid polylysine carboxymethylcellulose (poly ICLC) injection directly into the tumor followed by trans-hepatic artery embolization to the designated tumor. Patients receive poly ICLC subcutaneously on days 26, 35, 37, 42, 44, 49, and 51. Treatment repeats every 57 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months thereafter.

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Jersey
      • Newark, New Jersey, United States, 07101
        • Rutgrers University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Radiologically or histologically confirmed hepatocellular carcinoma

    • Stage III or IV primary disease

    • Recurrent, unresectable, or metastatic disease meeting any of the following criteria:

      • Pancreatic cancer that underwent prior surgical resection and progressed with recurrent metastatic disease to the liver
      • Gastric, colon, breast, or ovarian cancer or melanoma with metastatic disease to the liver
      • Primary or recurrent disease that cannot be surgically resected leaving the patient disease-free
  • Radiologically measurable disease

  • Ineligible for liver transplantation according to University of San Francisco listing criteria:

    • Single lesion > 6.5 cm
    • Three or more tumors > 4.5 cm
    • Cumulative tumor diameter > 8 cm

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 60-100%
  • ANC ≥ 1,500/mm³
  • Platelets ≥ 75,000/mm³
  • Creatinine ≤ 1.7 mg/dL
  • Total bilirubin ≤ 1.5 mg/dL
  • AST and ALT ≤ 3 times the upper limit of normal
  • INR < 1.5
  • LVEF ≥ 50%
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No serious concurrent infection or medical illness that would render the protocol treatment unsafe
  • LVEF ≥ 50%

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No concurrent steroids

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: poly ICLC
Drug: cyclophosphamide
Procedure: hepatic artery embolization
Radiation: 3-dimensional conformal radiation therapy
Drug: poly ICLC

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Overall tolerability
Time Frame: up to 90 days
up to 90 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Progression-free survival at 6, 12, and 24 months
Time Frame: up to 24 months
up to 24 months
Overall survival at 6, 12, and 24 months
Time Frame: up to 24 months
up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rutgers, The State University of New Jersey

Investigators

  • Study Chair: Andrew N. de la Torre, MD, UMDNJ University Hospital / St Joseph Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2007

Primary Completion (Anticipated)

February 1, 2014

Study Completion (Anticipated)

July 1, 2014

Study Registration Dates

First Submitted

November 2, 2007

First Submitted That Met QC Criteria

November 2, 2007

First Posted (Estimate)

November 4, 2007

Study Record Updates

Last Update Posted (Estimate)

January 14, 2014

Last Update Submitted That Met QC Criteria

January 11, 2014

Last Verified

January 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000573370
  • UMDNJ-0120070076

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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