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

January 7, 2019 updated by: The Rogosin Institute

Use of Mouse Renal Adenocarcinoma Cell-containing Agarose-agarose Macrobeads in the Treatment of Patients With End-stage, Treatment-resistant Epithelial-derived Cancer

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

56

Phase

  • 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 York
      • New York, New York, United States, 10021
        • NewYork Presbyterian Weill Cornell Medical Center

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 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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: Cancer macrobeads
Cancer Macrobead placement in abdominal cavity
Biological: Cancer Macrobead placement in abdominal cavity
8 macrobeads per kg
Other Names:
  • cancer macrobead

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD) of RENCA Macrobeads
Time Frame: 6 months

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.
6 months
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Time Frame: 6 months

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.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: From date of RENCA macrobeads implantation until date of death from any cause
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.
From date of RENCA macrobeads implantation until date of death from any cause

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tumor Marker Response
Time Frame: Prior to Implantation and Day 7, Day 14, Day 21 and Day 28 after each implantation
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.
Prior to Implantation and Day 7, Day 14, Day 21 and Day 28 after each implantation

Collaborators and Investigators

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

Sponsor

The Rogosin Institute

Investigators

  • Principal Investigator: Barry H Smith, MD, PhD, The Rogosin Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

January 1, 2005

Primary Completion (Actual)

December 1, 2012

Study Completion (Actual)

February 1, 2015

Study Registration Dates

First Submitted

January 26, 2006

First Submitted That Met QC Criteria

January 26, 2006

First Posted (Estimate)

January 27, 2006

Study Record Updates

Last Update Posted (Actual)

January 16, 2019

Last Update Submitted That Met QC Criteria

January 7, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 0407007343

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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