Open-Label Phase IIb Efficacy Trial of Cancer Macrobeads Compared to Best Supportive Care in Colorectal Cancer Patients

NCT02046174 | Completed Phase 2 Results DMC

• 2 other identifiers: RI-MB-2031310014396
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 4

Brief Summary

This is a clinical research study of an investigational (FDA IND-BB 10091) treatment for patients with advanced colorectal cancer that no longer responds to standard therapies. The treatment is being evaluated for its effect on tumor growth. It consists of the placement (implantation) of small beads that contain mouse renal adenocarcinoma cells (RENCA macrobeads). The cells in the macrobeads produce substances that have been shown to slow or stop the growth of tumors in experimental animals and veterinary patients. It has been tested in 31 human subjects with different types of cancers in a Phase I safety trial. Phase II studies in patients with colorectal, pancreatic or prostate cancers are in progress

Conditions

Colorectal Cancers

Keywords

colon; colorectal; rectal; cancer; macrobead; stage IV; metastatic; biological; mouse cells; new york; new jersey; clinical research

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  The primary objective of this study was to evaluate the efficacy of RENCA macrobead implantation as assessed by overall survival in subjects with treatment-resistant mCRC.

  From date of the most recent scan prior to the first macrobead implantation; assessed up to 32 months.

Secondary Outcomes (9)

• Performance Status (ECOG Score)

  Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2

• Activities of Daily Living (KPS Score)

  Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2

• Global Health Status

  Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2

• Physical Function

  Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2

• Role Function

  Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2

Other Outcomes (3)

• Tumor Marker Response (CEA and CA 19-9)

  Change from baseline up to and including day 90 post-Implant 1.

• Overall Survival by Tumor Marker Response

  30 months

• Necrosis Comparison of Tumors Using PET-CT Scan

  Day 90 post-Implant 1

Study Arms (2)

Macrobead Implantation Arm

EXPERIMENTAL

patients who will undergo up to 4 implantations of RENCA macrobeads (no less than 3 months apart), at an amount of 8 RENCA macrobeads per kilogram of body weight

Biological: RENCA macrobeads

Best Supportive Care Arm

NO INTERVENTION

patients who will receive, or continue receiving, best supportive care, defined as management of symptoms aimed at maintaining or improving quality of life, but not including approved therapies targeting the patient's malignancy

Interventions

RENCA macrobeads BIOLOGICAL

Also known as: mouse renal adenocarcinoma (RENCA) macrobeads, macrobead

Macrobead Implantation Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients in both treatment groups must meet all of the following criteria to be considered eligible to participate in the study:
• Adult men or women, aged 18 years or older, with histologically-confirmed, metastatic adenocarcinoma of the colon or rectum that has been proven to be resistant to available treatment options, including at least 2 such options from available chemotherapy, targeted, and/or other regimens.
• Radiographic evidence of disease progression.
• Life expectancy of at least 6 weeks, in the investigator's opinion, at the time disease progression is documented.
• Considered surgical candidates on the basis of co-morbidity risks, number and sites of metastases, and ability to undergo general anesthesia.
• Able to understand the risks of experimental therapy and provide written consent by signing the appropriate form.
• Patients in Group A must also meet all of the following additional criteria:
• ECOG performance status score of 0, 1, or 2.
• Adequate hematologic function, defined as follows:
• absolute neutrophil count (ANC) ≥1500 /mL
• hemoglobin ≥9 g/dL
• platelets ≥75,000 /mL
• Adequate hepatic function, defined as follows:
• bilirubin ≤1.5 times the upper limit of normal (x ULN)
• aspartate transaminase (AST) ≤3 x ULN, or ≤5 x ULN if liver metastases are present

You may not qualify if:

• Patients in either treatment group who meet any of the following criteria will be excluded from participating in the study:
• Hepatic blood flow abnormalities, i.e., portal vein hypertension and thrombosis, and/or a large volume of ascites.
• Concurrent cancer of any other type, except skin cancers other than melanoma.
• A positive test result for HIV or any hepatitis other than A at screening.
• Considered by the investigator to be unsuitable for participation in the study upon review of medical history, physical examination, or clinical laboratory test results.
• Patients in Group A who meet any of the following criteria will be excluded from participating in the study:
• Received FDA-approved chemotherapy within 3 weeks of Day 0, or bevacizumab (or similar drugs) within 4 weeks of Day 0, or radiation therapy at any site within 4 weeks of Day 0.
• Investigational anticancer therapy within 4 weeks of Day 0.
• Positive reaction to the skin test for allergy to mouse antigen.
• History of hypersensitivity reaction that, in the opinion of the investigator, poses an increased risk of an allergic reaction to the RENCA macrobeads, particularly any known allergy to murine antigens or body tissues.
• Ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmias (with the exception of well controlled atrial fibrillation), active bleeding, or psychiatric illness, or social situations that could interfere with the patient's ability to participate in the study.

Sponsors & Collaborators

• The Rogosin Institute: lead
• Vital Systems Inc.: collaborator

Study Sites (4)

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Weill Cornell Medical Center / The Rogosin Institute

New York, New York, 10021, United States

Location

Calvary Hospital

The Bronx, New York, 10461, United States

Location

The Ohio State University; OSU Comprehensive Cancer Center

Columbus, Ohio, 43210-1228, United States

Location

Related Publications (5)

• 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.

  PMID: 21266362 BACKGROUND

• 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.

  PMID: 21266363 BACKGROUND

• 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.

  PMID: 24025409 BACKGROUND

• Smith BH, Parikh T, Andrada ZP, Fahey TJ, Berman N, Wiles M, Nazarian A, Thomas J, Arreglado A, Akahoho E, Wolf DJ, Levine DM, Parker TS, Gazda LS, Ocean AJ. First-in-Human Phase 1 Trial of Agarose Beads Containing Murine RENCA Cells in Advanced Solid Tumors. Cancer Growth Metastasis. 2016 Aug 2;9:9-20. doi: 10.4137/CGM.S39442. eCollection 2016.

  PMID: 27499645 BACKGROUND

• Smith BH, Gazda LS, Fahey TJ, Nazarian A, Laramore MA, Martis P, Andrada ZP, Thomas J, Parikh T, Sureshbabu S, Berman N, Ocean AJ, Hall RD, Wolf DJ. Clinical laboratory and imaging evidence for effectiveness of agarose-agarose macrobeads containing stem-like cells derived from a mouse renal adenocarcinoma cell population (RMBs) in treatment-resistant, advanced metastatic colorectal cancer: Evaluation of a biological-systems approach to cancer therapy (U.S. FDA IND-BB 10091; NCT 02046174, NCT 01053013). Chin J Cancer Res. 2018 Feb;30(1):72-83. doi: 10.21147/j.issn.1000-9604.2018.01.08.

  PMID: 29545721 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Group B was only able to enroll 3/80 participants planned for the best supportive care management arm of this study. As per Group B investigators, the entry criteria were flagged as being impossible for reliable enrollment. Therefore, the results reported here focus on the Group A participants, those which were implanted with RENCA macrobeads.

Results Point of Contact

• Title: Betty-Jane Sloan, Clinical Research Manager
• Organization: The Rogosin Institute

bjsloan@nyp.org

646-317-0701

Study Officials

• Thomas J Fahey, III., M.D.

  Weill Cornell Medical Center / New York-Presbyterian Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2014
• First Posted: January 27, 2014
• Study Start: April 3, 2014
• Primary Completion: October 22, 2018
• Study Completion: October 22, 2018
• Last Updated: March 24, 2021
• Results First Posted: March 24, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)