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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Andrew de la Torre, Rutgers, The State University of New Jersey
ClinicalTrials.gov Identifier:
NCT00553683
First received: November 2, 2007
Last updated: January 11, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Colorectal Cancer
Gastric Cancer
Liver Cancer
Melanoma (Skin)
Metastatic Cancer
Ovarian Cancer
Pancreatic Cancer
Drug: cyclophosphamide
Drug: poly ICLC
Procedure: hepatic artery embolization
Radiation: 3-dimensional conformal radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Rutgers, The State University of New Jersey:

Primary Outcome Measures:
  • Overall tolerability [ Time Frame: up to 90 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression-free survival at 6, 12, and 24 months [ Time Frame: up to 24 months ] [ Designated as safety issue: No ]
  • Overall survival at 6, 12, and 24 months [ Time Frame: up to 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: October 2007
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: poly ICLC Drug: cyclophosphamide Drug: poly ICLC Procedure: hepatic artery embolization Radiation: 3-dimensional conformal radiation therapy

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00553683

Locations
United States, New Jersey
Rutgrers University Hospital
Newark, New Jersey, United States, 07101
Sponsors and Collaborators
Rutgers, The State University of New Jersey
Investigators
Study Chair: Andrew N. de la Torre, MD UMDNJ University Hospital / St Joseph Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Andrew de la Torre, Associate Professor, Rutgers, The State University of New Jersey
ClinicalTrials.gov Identifier: NCT00553683     History of Changes
Other Study ID Numbers: CDR0000573370, UMDNJ-0120070076
Study First Received: November 2, 2007
Last Updated: January 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Rutgers, The State University of New Jersey:
stage IV pancreatic cancer
adult primary hepatocellular carcinoma
advanced adult primary liver cancer
recurrent adult primary liver cancer
localized unresectable adult primary liver cancer
recurrent pancreatic cancer
recurrent colon cancer
recurrent breast cancer
recurrent gastric cancer
recurrent ovarian epithelial cancer
recurrent melanoma
stage IV breast cancer
stage IV gastric cancer
stage IV colon cancer
stage IV ovarian epithelial cancer
stage IV melanoma
liver metastases

Additional relevant MeSH terms:
Breast Neoplasms
Colorectal Neoplasms
Liver Neoplasms
Stomach Neoplasms
Melanoma
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Ovarian Neoplasms
Pancreatic Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Liver Diseases
Stomach Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplastic Processes

ClinicalTrials.gov processed this record on August 20, 2014