Open-Label Phase 2 Efficacy Trial Of Cancer Macrobeads In Patients With Treatment-Resistant Pancreatic/Colorectal Cancer

Study Overview

Open-Label Phase 2 Efficacy Trial of Cancer Macrobeads in Patients With Treatment-Resistant Pancreatic/Colorectal Cancer

This is a clinical research study of an investigational (FDA BB-IND 10091) treatment for patients with pancreatic cancer (all stages) and 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.

This is an open-label Phase 2 clinical trial. The study will have a duration of 12 months and involve a potential total of four macrobead implants for each enrolled patient, with the implants being no less than three months apart. The RENCA macrobeads are implanted intraperitoneally, using laparoscopic surgical procedures. The macrobeads remain permanently within the peritoneal cavity, even if patients withdraw from the study and/or begin new therapy (e.g. chemotherapy). After the formal phase of the trial is completed, subjects will be followed for life. The intent of this Phase 2 trial is to assess efficacy, safety, and tolerability of RENCA macrobeads. Screening occurs within 28 days prior to first implantation. Enrolled patients are treated with a dose of 8 RENCA macrobeads per kilogram of body weight and observed for a minimum of 3 months prior to the next implantation. A maximum of 4 implantation procedures is possible. Day 0 is the day of implantation. Prior to the start of the study, the Investigators ensured that the protocol and any attendant documentation were approved, in writing, by the Institutional Review Board. The study was conducted in compliance with the International Conference on Harmonization (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use Good Clinical Practice Guidelines (E6 [R1]) for conducting, recording, and reporting studies, as well as for archiving essential documents. The Investigators, the Medical Monitor of the sponsor, and the Data Safety Monitoring Board were responsible for monitoring safety parameters collected in the study. They, collectively, provided oversight and monitoring of the safety of the participants in the study.

Pancreatic Adenocarcinoma Non-resectable
Pancreatic Adenocarcinoma Metastatic
Colorectal Cancer Metastatic

BIOLOGICAL: RENCA macrobeads

0911010739

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 Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2010-01-20	Results First Submitted 2021-01-08	Last Update Submitted that met QC Criteria 2021-04-23
First Submitted that Met QC Criteria 2010-01-20	Results First Submitted that Met QC Criteria 2021-04-22	Last Update Posted (ACTUAL) 2021-05-12
First Posted (ACTUAL) 2010-01-21	Results First Posted 2021-04-23	Last Verified 2021-04

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Macrobead Implantation patients 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

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Macrobead Implantation

patients 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

Primary Outcome Measures	Measure Description	Time Frame
Overall Survival - Based on Most Recent Scan	The primary efficacy outcome is post-implantation all-cause mortality, where time to death is defined as the time from the most recent scan prior to first implantation (time of origin, To) to death from any cause.	From date of the most recent scan (disease progression) prior to the first macrobead implantation; assessed up to 32 months.

Secondary Outcome Measures	Measure Description	Time Frame
Overall Survival - Based on 1st Implant	The secondary efficacy objective was to evaluate overall survival calculated using the time from first RENCA macrobead implantation to death from any cause.	From date of the first RENCA macrobead implant; assessed up to 32 months.
Overall Survival - Based on Stage IV Disease Diagnosis	The secondary efficacy objective was to evaluate overall survival calculated using the time from Stage IV disease diagnosis to death from any cause.	From date of Stage IV disease diagnosis up to 126 months; up to 32 months from first RENCA macrobead implant.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Histologically confirmed adenocarcinoma of the pancreas, colon or rectum.
Radiographic evidence of metastatic cancer of the colon or rectum.
Pancreatic cancer that is unresectable or already metastatic, or colorectal cancer that has failed available approved treatment modalities.
For pancreatic cancer patients, prior chemotherapy is not required; for colon and rectal cancer patients must have failed available chemotherapy/targeted regimens. There were no limits to the number of prior chemotherapeutic regimens.
The patient had evidence of progressive disease defined as at least one of the following:

All clinically significant toxic effects (excluding alopecia) of prior surgery, radiotherapy, or hormonal therapy were resolved to ≤ Grade 1 based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (NCI CTCAE v.3.0) with the exception of neuropathy, which was resolved to ≤ Grade 2.
Performance status (ECOG PS) 0-2.
Adequate hematologic function, minimum requirements:

Adequate hepatic function, defined as follows:

Adequate renal function, defined as serum creatinine ≤ 2.0 mg/dL.
Adequate coagulation function, defined as follows:

Life expectancy of at least 6 weeks.
For females of childbearing potential, a negative pregnancy test.
Agrees to contraceptive use (barrier method) while on study, if sexually active.
Provided signed informed consent.

Any condition presenting an unacceptably high anesthetic or surgical risk, based on current anesthesia/general surgery standards.
Positive test for HIV, hepatitis B, C, or E.
Cognitive impairment such as to preclude informed consent.
Hypersensitivity reaction that, in the opinion of the investigators posed an increased risk of an allergy to the macrobeads, particularly any known allergy to murine antigens or body tissues.
Surgical treatment or chemotherapy within three weeks of scheduled macrobead implantation or within four weeks of bevacizumab (or similar drugs), or radiation therapy within four weeks of scheduled macrobead implantation.
Investigational medication(s)/therapies for respective tumor within one month of baseline evaluation.
Inadequate hematologic function, defined as follows:

Inadequate hepatic function, defined as follows:

Inadequate renal function, defined as serum creatinine > 2.0 mg/dL.
Inadequate coagulation function, defined as follows:

Hepatic blood flow abnormalities, portal vein hypertension and thrombosis, and/or large-volume ascites.
Concurrent cancer of any other type except skin cancer (excluding melanoma).
Ongoing or active infection, congestive heart failure, unstable angina, serious cardiac arrhythmias, psychiatric illness, difficult social situations not permitting reliable participation, active bleeding.
As a result of the medical history, examination, or blood testing, the investigator considers the patient unfit for the study.

Collaborators and Investigators

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

Vital Systems Inc.

Investigators

PRINCIPAL_INVESTIGATOR: Thomas Fahey, III., MD, Weill Cornell Medical Center / New York-Presbyterian Hospital

Publications

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

General Publications

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.
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, 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.
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.
Martis PC, Dudley AT, Bemrose MA, Gazda HL, Smith BH, Gazda LS. MEF2 plays a significant role in the tumor inhibitory mechanism of encapsulated RENCA cells via EGF receptor signaling in target tumor cells. BMC Cancer. 2018 Dec 4;18(1):1217. doi: 10.1186/s12885-018-5128-5.
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.

Learn

Resources

PatientS

Caregivers

Clinical Trial Record