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

• ClinicalTrials.gov Identifier: NCT00283075
• Recruitment Status: Completed
• First Posted: January 27, 2006
• Results First Posted: March 10, 2016
• Last Update Posted: January 16, 2019
• Sponsor: The Rogosin Institute
• Information provided by (Responsible Party): The Rogosin Institute

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Intraabdominal Cancers (Various Types)	Biological: Cancer Macrobead placement in abdominal cavity	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 56 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: January 2005
• Actual Primary Completion Date: December 2012
• Actual Study Completion Date: February 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cancer macrobeads; Cancer Macrobead placement in abdominal cavity	Biological: Cancer Macrobead placement in abdominal cavity; 8 macrobeads per kg; Other Name: cancer macrobead

Outcome Measures

Primary Outcome Measures :

1. 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.

2. 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.

Secondary Outcome Measures :

1. 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.

Other Outcome Measures:

1. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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:

DeWys WD. Studies correlating the growth rate of a tumor and its metastases and providing evidence for tumor-related systemic growth-retarding factors. Cancer Res. 1972 Feb;32(2):374-9.

Fisher B, Gunduz N, Coyle J, Rudock C, Saffer E. Presence of a growth-stimulating factor in serum following primary tumor removal in mice. Cancer Res. 1989 Apr 15;49(8):1996-2001.

Prehn RT. The inhibition of tumor growth by tumor mass. Cancer Res. 1991 Jan 1;51(1):2-4. Review.

Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001 Nov 1;414(6859):105-11. Review.

Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8. Epub 2003 Mar 10. Erratum in: Proc Natl Acad Sci U S A. 2003 May 27;100(11):6890.

Smith BH, Gazda LS, Conn BL, Jain K, Asina S, Levine DM, Parker TS, Laramore MA, Martis PC, Vinerean HV, David EM, Qiu S, North AJ, Couto CG, Post GS, Waters DJ, Cordon-Cardo C, Hall RD, Gordon BR, Diehl CH, Stenzel KH, Rubin AL. Hydrophilic agarose macrobead cultures select for outgrowth of carcinoma cell populations that can restrict tumor growth. Cancer Res. 2011 Feb 1;71(3):725-35. doi: 10.1158/0008-5472.CAN-10-2258. Epub 2011 Jan 24.

Smith BH, Gazda LS, Conn BL, Jain K, Asina S, Levine DM, Parker TS, Laramore MA, Martis PC, Vinerean HV, David EM, Qiu S, Cordon-Cardo C, Hall RD, Gordon BR, Diehl CH, Stenzel KH, Rubin AL. Three-dimensional culture of mouse renal carcinoma cells in agarose macrobeads selects for a subpopulation of cells with cancer stem cell or cancer progenitor properties. Cancer Res. 2011 Feb 1;71(3):716-24. doi: 10.1158/0008-5472.CAN-10-2254. Epub 2011 Jan 24.

Gazda LS, Martis PC, Laramore MA, Bautista MA, Dudley A, Vinerean HV, Smith BH. Treatment of agarose-agarose RENCA macrobeads with docetaxel selects for OCT4(+) cells with tumor-initiating capability. Cancer Biol Ther. 2013 Dec;14(12):1147-57. doi: 10.4161/cbt.26455. Epub 2013 Sep 12.

• Responsible Party: The Rogosin Institute
• ClinicalTrials.gov Identifier: NCT00283075
• Other Study ID Numbers: 0407007343
• First Posted: January 27, 2006
• Results First Posted: March 10, 2016
• Last Update Posted: January 16, 2019
• Last Verified: January 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by The Rogosin Institute:

intraabdominal cancer (carcinomas); agarose macrobeads; mouse kidney cancer cells; cancer cell growth inhibition