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

NCT ID: NCT02046174

Last Updated: 2021-03-24

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-04-03

Study Completion Date

2018-10-22

Brief Summary

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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

Detailed Description

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This is a Phase IIb, multicenter, nonrandomized, open-label study with RENCA macrobeads in patients with treatment-resistant, metastatic colorectal carcinoma to determine the effect of RENCA macrobead implantation on overall survival compared with best supportive care.

Two treatment groups will be enrolled in this study, as follows:

* Group A (n=40) - patients who will undergo up to 4 implantations of RENCA macrobeads (no less than 3 months apart), at a dosage level of 8 RENCA macrobeads per kilogram of body weight
* Group B (n=80) - patients who had previously decided (independently of this study) to 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

Conditions

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Colorectal Cancers

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Macrobead Implantation Arm

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

Group Type EXPERIMENTAL

RENCA macrobeads

Intervention Type BIOLOGICAL

Best Supportive Care Arm

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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RENCA macrobeads

Intervention Type BIOLOGICAL

Other Intervention Names

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mouse renal adenocarcinoma (RENCA) macrobeads macrobead

Eligibility Criteria

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Inclusion Criteria

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:

1. absolute neutrophil count (ANC) ≥1500 /mL
2. hemoglobin ≥9 g/dL
3. platelets ≥75,000 /mL
* Adequate hepatic function, defined as follows:

1. bilirubin ≤1.5 times the upper limit of normal (x ULN)
2. aspartate transaminase (AST) ≤3 x ULN, or ≤5 x ULN if liver metastases are present
3. alanine transaminase (ALT) ≤3, x ULN, or ≤5 x ULN if liver metastases are present
* Adequate renal function, defined as creatinine ≤2.0 mg/dL.
* Adequate coagulation function, defined as follows:

1. International Normalized Ratio (INR) ≤1.5 or between 2 and 3 if the patient is receiving anticoagulation
2. Partial Thromboplastin Time (PTT) ≤5 seconds above the ULN Note: Patients receiving full-dose anticoagulation therapy must have received a stable dose of oral anticoagulant therapy or low-molecular-weight heparin.
* Clinically significant toxic effects of chemotherapy (excluding alopecia), radiotherapy, hormonal therapy, or prior surgery must have resolved to Grade 1 or better, with the exception of peripheral neuropathy, which must have resolved to Grade 2 or better.
* Female participants of childbearing potential must have had a negative serum pregnancy test at screening; and must also agree to contraceptive use while on study if sexually active. Male subjects and their partners must have agreed to use condoms.

Exclusion Criteria

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vital Systems Inc.

OTHER

Sponsor Role collaborator

The Rogosin Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Thomas J Fahey, III., M.D.

Role: PRINCIPAL_INVESTIGATOR

Weill Cornell Medical Center / New York-Presbyterian Hospital

Locations

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University of Kansas Cancer Center

Westwood, Kansas, United States

Site Status

Weill Cornell Medical Center / The Rogosin Institute

New York, New York, United States

Site Status

Calvary Hospital

The Bronx, New York, United States

Site Status

The Ohio State University; OSU Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 21266362 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21266363 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24025409 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27499645 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29545721 (View on PubMed)

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

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1310014396

Identifier Type: OTHER

Identifier Source: secondary_id

RI-MB-203

Identifier Type: -

Identifier Source: org_study_id

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