Mouse Cancer Cell-containing Macrobeads in the Treatment of Human Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
The Rogosin Institute
ClinicalTrials.gov Identifier:
NCT00283075
First received: January 26, 2006
Last updated: February 11, 2016
Last verified: February 2016
  Purpose
This is a phase 1 trial to evaluate the safety and toxicity of mouse kidney cancer cell-containing agarose-agarose macrobeads that are implanted in the abdominal cavity as a proposed biological treatment of patients with end-stage, treatment-resistant cancer. The macrobeads have been extensively tested in tumor models in mice and rats, as well as in forty-five veterinary patients (cats and dogs) with naturally occurring tumors of various types including breast cancer, prostate cancer, liver cancer, and lymphoma with clear tumor responses and no significant detectable toxicity.

Condition Intervention Phase
Intraabdominal Cancers (Various Types)
Biological: Cancer Macrobead placement in abdominal cavity
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Use of Mouse Renal Adenocarcinoma Cell-containing Agarose-agarose Macrobeads in the Treatment of Patients With End-stage, Treatment-resistant Epithelial-derived Cancer

Resource links provided by NLM:


Further study details as provided by The Rogosin Institute:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of RENCA Macrobeads [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

    Dose limiting toxicity (DLT) was defined as:

    • any Grade 2 allergic reaction of generalized urticaria or any other Grade ≥ 3 allergic reaction;
    • any Grade ≥ 3 infection and
    • any Grade ≥ 3 local (intraperitoneal) reaction and any Grade ≥ 3 hematologic or non- hematologic reaction.

    This definition of DLT is in accord with the NCI CTCAE v3.0.

    Maximum tolerated dose (MTD) was to be identified if, within a cohort, > 1 subject out of the first 3, or 2 subjects out of 5 experienced DLT. In such a case, the MTD will have been exceeded, and the administration of the study agent was to cease. MTD would not be considered to have been reached if no DLTs were observed.


  • Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

    Dose limiting toxicity (DLT) was defined as:

    • any Grade 2 allergic reaction of generalized urticaria or any other Grade ≥ 3 allergic reaction;
    • any Grade ≥ 3 infection and
    • any Grade ≥ 3 local (intraperitoneal) reaction and any Grade ≥ 3 hematologic or non- hematologic reaction.

    This definition of DLT is in accord with the NCI CTCAE v3.0.



Secondary Outcome Measures:
  • Overall Survival [ Time Frame: From date of RENCA macrobeads implantation until date of death from any cause ] [ Designated as safety issue: No ]
    Overall Survival (OS) was measured as date of first implantation to date of death of any cause, and was analyzed using the Kaplan-Meier method.


Other Outcome Measures:
  • Tumor Marker Response [ Time Frame: Prior to Implantation and Day 7, Day 14, Day 21 and Day 28 after each implantation ] [ Designated as safety issue: No ]
    Tumor marker response after the first implantation with RENCA macrobeads. Responders showed at least a 20% decrease from baseline in Cancer Antigen 19-9 (CA19-9) or Carcinoembryonic Antigen (CEA); Non-responders do not show at least a 20% decrease from baseline in CA19-9 or CEA.


Enrollment: 56
Study Start Date: January 2005
Study Completion Date: February 2015
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cancer macrobeads
Cancer Macrobead placement in abdominal cavity
Biological: Cancer Macrobead placement in abdominal cavity
8 macrobeads per kg
Other Name: cancer macrobead

Detailed Description:

Cancer in its various forms continues to be a major U.S. health problem, accounting for 550,000 deaths a year, as well as much disability and suffering. Treatment for cancer has traditionally consisted of three modalities: surgery, radiation therapy, and chemotherapy. Advances with all three modalities over the years have produced long-term remissions and/or cures in certain types of cancer such as the leukemias, and prolonged survival for many other patients. Much remains to be accomplished, however, especially with respect to the treatment of solid tumors, including some of the most common cancers such as those of the lung, colon, breast, ovary, prostate and kidney. New types of less toxic and debilitating therapy are needed.

Among the therapeutic possibilities currently being explored, those that involve biological control mechanisms seem both promising and attractive. Although it has long been thought that cancer cells are not subject to the same regulatory growth control mechanisms that function in normal cells, there is a substantial body of evidence that they can respond to feedback signals telling them to slow or stop their growth. In addition, it has been determined that a relatively small population of cells within a tumor (cancer "stem" or progenitor cells) are responsible for continued tumor growth and that it is these cells that must be controlled if biological anti-tumor therapy is to be effective.

The proposed cancer treatment being tested in this Phase 1 clinical trial is based on the concept that tumor growth can be controlled by tumor mass or signals that indicate that such mass is present. In this case, however, the induction of the growth-slowing signals is brought about not by tumor mass, but by placing mouse kidney cancer cells in an agarose matrix, which both selects for cancer progenitor cells and also causes them to produce and release signals that inhibit the growth of freely growing cancer cells of the same or different type in a laboratory dish or in a tumor-bearing animal or human (i.e. is also not species-specific). This approach has proven both safe and effective in animal models and veterinary patients, and it is now in the first stage of human testing. With Phase 1 completed, we are now implementing Phase 2 efficacy trials that for the present are focused on colorectal cancer, pancreatic cancer, and prostate cancer. The Phase 1 trial remains open to a range of epithelial-derived cancer.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • End-stage, treatment resistant epithelial-derived cancer (carcinoma) arising originally within the abdominal cavity with expected minimum six-month survival

Exclusion Criteria:

  • Multiple intraabdominal metastases or carcinomatosis or other medical conditions indicating that the procedure would be of too high a risk for the individual
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00283075

Locations
United States, New York
NewYork Presbyterian Weill Cornell Medical Center
New York, New York, United States, 10021
Sponsors and Collaborators
The Rogosin Institute
Investigators
Principal Investigator: Barry H Smith, MD, PhD The Rogosin Institute
  More Information

Publications:

Responsible Party: The Rogosin Institute
ClinicalTrials.gov Identifier: NCT00283075     History of Changes
Other Study ID Numbers: 0407007343 
Study First Received: January 26, 2006
Results First Received: October 26, 2015
Last Updated: February 11, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by The Rogosin Institute:
intraabdominal cancer (carcinomas)
agarose macrobeads
mouse kidney cancer cells
cancer cell growth inhibition

ClinicalTrials.gov processed this record on July 24, 2016