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

NCT01053013 | Completed Phase 2 Results DMC

• 1 other identifier: 0911010739
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pancreatic Adenocarcinoma Non-resectable; Pancreatic Adenocarcinoma Metastatic; Colorectal Cancer Metastatic

Keywords

macrobead; biological; mouse cells

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Overall Survival - Based on 1st Implant

  From date of the first RENCA macrobead implant; assessed up to 32 months.

• Overall Survival - Based on Stage IV Disease Diagnosis

  From date of Stage IV disease diagnosis up to 126 months; up to 32 months from first RENCA macrobead implant.

Other Outcomes (27)

• Necrosis Comparison of Tumors Using PET-CT Scan

  Baseline vs. Day 90 post-Implant 1

• Tumor Marker Response of mCRC Participants

  Change from baseline up to and including day 30 post-Implant 1

• Tumor Marker Response of Pancreatic Cancer Participants

  Change from baseline up to and including day 30 post-Implant 1.

Study Arms (1)

Macrobead Implantation

EXPERIMENTAL

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

Interventions

RENCA macrobeads BIOLOGICAL

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

Macrobead Implantation

Eligibility Criteria

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

You may qualify if:

• 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:
• Progressive measurable disease using conventional solid tumor criteria.
• Increasing tumor markers and/or activity on positron emission tomography / standard uptake value (PET/SUV) measurement.
• 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:
• absolute neutrophil count (ANC) ≥ 1500/mL
• hemoglobin ≥ 9 g/dL
• platelets ≥ 100,000/mL
• Adequate hepatic function, defined as follows:
• bilirubin ≤ 1.5 times the upper limit of normal (ULN)

You may not qualify if:

• 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:
• ANC \< 1500/mL
• hemoglobin \< 9 g/dL
• platelets \< 100,000/mL
• Inadequate hepatic function, defined as follows:
• bilirubin \> 1.5 times the ULN
• AST and ALT \> 3 times the ULN or \> 5 times the ULN, if liver metastases present
• Inadequate renal function, defined as serum creatinine \> 2.0 mg/dL.
• Inadequate coagulation function, defined as follows:

Sponsors & Collaborators

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

Study Sites (1)

Weill Cornell Medical Center / The Rogosin Institute

New York, New York, 10021, United States

Location

Related Publications (6)

• 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

• 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, 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

• 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

• 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.

  PMID: 30514247 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

Limitations and Caveats

Limitations of this study include the lack of non-macrobead implanted comparator groups for pancreatic and mCRC subjects, the small sample sizes of both groups, the limited number of subjects with \>1 implant and the potential for various biases due to the non-randomized study design.

Results Point of Contact

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

bjsloan@nyp.org

646-317-0701

Study Officials

• Thomas Fahey, III., MD

  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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2010
• First Posted: January 21, 2010
• Study Start: April 15, 2010
• Primary Completion: April 16, 2016
• Study Completion: April 16, 2016
• Last Updated: May 12, 2021
• Results First Posted: April 23, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)