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

Breast Cancer Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00553683
• Other study ID #: CDR0000573370
• Secondary ID: UMDNJ-0120070076
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: November 2, 2007
• Last updated: January 11, 2014
• Start date: October 2007
• Est. completion date: July 2014

Study information

• Verified date: January 2014
• Source: Rutgers, The State University of New Jersey
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: July 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Breast Cancer
• Colorectal Cancer
• Gastric Cancer
• Liver Cancer
• Liver Neoplasms
• Melanoma (Skin)
• Metastatic Cancer
• Neoplasm Metastasis
• Neoplasms
• Neoplasms, Second Primary
• Ovarian Cancer
• Pancreatic Cancer
• Pancreatic Neoplasms
• Stomach Neoplasms

Intervention

Drug:
• cyclophosphamide

• poly ICLC

Procedure:
• hepatic artery embolization

Radiation:
• 3-dimensional conformal radiation therapy

Locations

Country	Name	City	State
United States	Rutgrers University Hospital	Newark	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Rutgers, The State University of New Jersey

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall tolerability		up to 90 days	Yes
Secondary	Progression-free survival at 6, 12, and 24 months		up to 24 months	No
Secondary	Overall survival at 6, 12, and 24 months		up to 24 months	No