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

An Open-Label Phase 2 Efficacy Trial of the Implantation of Mouse Renal Adenocarcinoma Cell-Containing Agarose-Agarose Macrobeads in the Treatment of Patients With Treatment-Resistant, Metastatic Pancreatic or 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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer Metastatic; Pancreatic Adenocarcinoma Metastatic; Pancreatic Adenocarcinoma Non-resectable
• Intervention / Treatment: Biological: RENCA macrobeads

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical Center / The Rogosin Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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:

  1. Progressive measurable disease using conventional solid tumor criteria.
  2. 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:

  1. absolute neutrophil count (ANC) ≥ 1500/mL
  2. hemoglobin ≥ 9 g/dL
  3. platelets ≥ 100,000/mL

• Adequate hepatic function, defined as follows:

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

• Adequate coagulation function, defined as follows:

  1. an international normalized ratio (INR) ≤ 1.5
  2. a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN, unless on anti-coagulant therapy
  3. patients receiving full-dose anticoagulation therapy were eligible provided they met all other criteria, were on a stable dose or anticoagulant therapy or low molecular weight heparin (and if on warfarin had a therapeutic INR between 2-3)
• 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.

Exclusion Criteria:

• 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:

  1. ANC < 1500/mL
  2. hemoglobin < 9 g/dL
  3. platelets < 100,000/mL

• Inadequate hepatic function, defined as follows:

  1. bilirubin > 1.5 times the ULN
  2. 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:

  1. INR > 1.5
  2. PTT > 5 seconds (unless on anti-coagulant therapy)
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

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; Other Names: mouse renal adenocarcinoma (RENCA) macrobeads; macrobead; cancer macrobead

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Outcome Measure	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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Necrosis Comparison of Tumors Using PET-CT Scan	Tumors were assessed by positron emission tomography (PET)-CT scan at baseline and day 90 following the first RENCA macrobead implantation. The use of [13]F-fluorodeoxyglucose (FDG) uptake for the detection of lesions >1 cm in diameter allowed evaluation of metabolic activity. Decreases in FDG uptake were indicative of metabolic suppression of the tumor. The use of PET-CT scanning indicated anatomical localization, approximate size/volume of primary tumor and metastatic lesion(s), and assessment of metabolic activity of the tumor (as an indicator of metabolic health and necrosis). Disease state is reported as a function of Tumor measurement divided by SUVmax. Changes were assessed between day 90 post RENCA macrobead implant and baseline values. Patients with no change = stable; patients with decreased values = decreased/necrosis, and patients with increased values = increased.	Baseline vs. Day 90 post-Implant 1
Tumor Marker Response of mCRC Participants	Tumor markers included serum carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9), and were assessed on all participants with mCRC at baseline and at subsequent evaluation points to further assess tumor response to RENCA macrobead implantation. A tumor marker response was defined as a greater than or equal to 20% decrease in one or both of CEA or CA 19-9.	Change from baseline up to and including day 30 post-Implant 1
Tumor Marker Response of Pancreatic Cancer Participants	Tumor markers included serum carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9), and were assessed on all participants with pancreatic cancer at baseline and at subsequent evaluation points to further assess tumor response to RENCA macrobead implantation. A tumor marker response was defined as a greater than or equal to 20% decrease in one or both of CEA or CA 19-9.	Change from baseline up to and including day 30 post-Implant 1.
C-reactive Protein Levels in mCRC Participants	C-reactive protein (CRP) is one of three inflammatory markers assessed during this study. CRP levels were assessed as a marker of systemic inflammatory processes.	Day 0, 14, 30, 60 post-Implant 1 and Day 0, 14, 30, 60 post-Implant 2 (when applicable).
C-Reactive Protein Levels in Pancreatic Cancer Participants	C-reactive protein (CRP) is one of three inflammatory markers assessed during this study. CRP levels were assessed as a marker of systemic inflammatory processes.	Day 0, 14, 30, 60 post-Implant 1 and Day 0, 14, 30, 60 post-Implant 2 (when applicable).
Erythrocyte Sedimentation Rate in mCRC Participants	Erythrocyte sedimentation rate (ESR) is one of three inflammatory markers assessed during this study. ESR was assessed as a marker of systemic inflammatory processes.	Day 0, 14, 30, 60 post-Implant 1 and Day 0, 14, 30, 60 post-Implant 2 (when applicable).
Erythrocyte Sedimentation Rate in Pancreatic Cancer Participants	Erythrocyte sedimentation rate (ESR) is one of three inflammatory markers assessed during this study. ESR was assessed as a marker of systemic inflammatory processes.	Day 0, 14, 30, 60 post-Implant 1 and Day 0, 14, 30, 60 post-Implant 2 (when applicable).
Cancer Antigen 125 Levels in mCRC Participants	Cancer Antigen 125 (CA 125) is one of three inflammatory markers assessed during this study. CA 125 was used to monitor more localized intra-abdominal/peritoneal inflammatory processes related to the placement of the RENCA macrobeads or, in some cases, the intraperitoneal spread of tumor.	Day 0, 14, 30, 60 post-Implant 1 and Day 0, 14, 30, 60 post-Implant 2 (when applicable).
Cancer Antigen 125 Levels in Pancreatic Cancer Participants	Cancer Antigen 125 (CA 125) is one of three inflammatory markers assessed during this study. CA 125 was used to monitor more localized intra-abdominal/peritoneal inflammatory processes related to the placement of the RENCA macrobeads or, in some cases, the intraperitoneal spread of tumor.	Day 0, 14, 30, 60 post-Implant 1 and Day 0, 14, 30, 60 post-Implant 2 (when applicable).
Performance Status (ECOG Score) of mCRC Participants	The Eastern Cooperative Oncology Group (ECOG) performance scale is a 5-point scale, where 0 denotes perfect health and 5 is death. It is used by clinicians to assess disease progression and how the disease is affecting the daily living abilities of the patient. The ECOG Performance Status scores are defined as follows: 0: Fully active, able to carry on all pre-disease activities without restriction.; Restricted in physical strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g. light house work, office work).; Ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50% of waking hours.; Capable of only limited self-care, confined to bed or chair 50% or more of waking hours.; Completely disabled, cannot carry on any self-care, totally confined to bed or chair.; Death	Baseline; Day 14, 30, 60 post-Implant; Day 14, 30, 60 post-Implant 2
Performance Status (ECOG Score) of Pancreatic Cancer Participants	The Eastern Cooperative Oncology Group (ECOG) performance scale is a 5-point scale, where 0 denotes perfect health and 5 is death. It is used by clinicians to assess disease progression and how the disease is affecting the daily living abilities of the patient. The ECOG Performance Status scores are defined as follows: 0: Fully active, able to carry on all pre-disease activities without restriction.; Restricted in physical strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g. light house work, office work).; Ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50% of waking hours.; Capable of only limited self-care, confined to bed or chair 50% or more of waking hours.; Completely disabled, cannot carry on any self-care, totally confined to bed or chair.; Death	Baseline; Day 14, 30, 60 post-Implant; Day 14, 30, 60 post-Implant 2
Activities of Daily Living (KPS Score) of mCRC Participants	Karnofsky Performance Status (KPS) is a self-rated scale that measures the participant's ability to perform daily functions, ranging from 0 ("dead") to 100 ("normal, no complaints, no evidence of disease). Karnofsky scores are defined as follows: 100: Normal; no complaints; no evidence of disease 90: Able to carry on normal activity with effort, minor sign or symptoms of disease 80: Normal activity with effort; some sign or symptoms of disease 70: Cares for self; unable to carry on normal activity or do active work 60: Requires occasional assistance, but is able to care for most personal needs 50: Requires considerable assistance and frequent medical care 40: Disabled; requires special care and assistance 30: Severely disabled; hospitalization is indicated, although death is not imminent 20: Very sick; hospitalization/active support treatment is necessary 10: Moribund; fatal processes progressively worsening 0: Dead	Baseline; Day 14, 30, 60 Post-Implant 1; Day 14, 30, 60 post-Implant 2
Activities of Daily Living (KPS Score) for Pancreatic Cancer Participants	Karnofsky Performance Status (KPS) is a self-rated scale that measures the participant's ability to perform daily functions, ranging from 0 ("dead") to 100 ("normal, no complaints, no evidence of disease). Karnofsky scores are defined as follows: 100: Normal; no complaints; no evidence of disease 90: Able to carry on normal activity with effort, minor sign or symptoms of disease 80: Normal activity with effort; some sign or symptoms of disease 70: Cares for self; unable to carry on normal activity or do active work 60: Requires occasional assistance, but is able to care for most personal needs 50: Requires considerable assistance and frequent medical care 40: Disabled; requires special care and assistance 30: Severely disabled; hospitalization is indicated, although death is not imminent 20: Very sick; hospitalization/active support treatment is necessary 10: Moribund; fatal processes progressively worsening 0: Dead	Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2
Global Health Status of mCRC Participants	The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales, three symptom scales, a global health status score, and six single items. The Global Health Status is assessed from 2 of the 30 questions (Question 29 and 30), whose response score ranges on a 7 point scale. The score for physical function is calculated based on the average score from these 2 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor) and the maximum value is 100 (best outcome, excellent). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome.	Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2
Global Health Status of Pancreatic Cancer Participants	The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales, three symptom scales, a global health status score, and six single items. The Global Health Status is assessed from 2 of the 30 questions (Question 29 and 30), whose response score ranges on a 7 point scale. The score for physical function is calculated based on the average score from these 2 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor) and the maximum value is 100 (best outcome, excellent). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome.	Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2
Physical Function of mCRC Participants	The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including physical function), three symptom scales, a global health status score, and six single items. Physical Function is assessed from 5 of the 30 questions (Questions 1-5), whose response score ranges on a 4 point scale. The score for physical function is calculated based on the average score from these 5 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome.	Baseline; Day 30, 60 post-Implant 1; Day 30, 60 post-Implant 2
Physical Function of Pancreatic Cancer Participants	The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including physical function), three symptom scales, a global health status score, and six single items. Physical Function is assessed from 5 of the 30 questions (Questions 1-5), whose response score ranges on a 4 point scale. The score for physical function is calculated based on the average score from these 5 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome.	Baseline; Day 30, 60 post-Implant 1; Day 30, 60 post-Implant 2
Role Function of mCRC Participants	The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including role function), three symptom scales, a global health status score, and six single items. Role Function is assessed from 2 of the 30 questions (Questions 6 and 7), whose response score ranges on a 4 point scale. The score for role function is calculated based on the average score from these 2 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome.	Baseline; Day 30, 60 post-Implant 1; Day 30, 60 post-Implant 2
Role Function of Pancreatic Cancer Participants	The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including role function), three symptom scales, a global health status score, and six single items. Role Function is assessed from 2 of the 30 questions (Questions 6 and 7), whose response score ranges on a 4 point scale. The score for role function is calculated based on the average score from these 2 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome.	Baseline; Day 30, 60 post-Implant 1; Day 30, 60 post-Implant 2
Emotional Function of mCRC Participants	The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including emotional function), three symptom scales, a global health status score, and six single items. Emotional Function is assessed from 4 of the 30 questions (Questions 21-24), whose response score ranges on a 4 point scale. The score for role function is calculated based on the average score from these 4 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome.	Baseline; Day 30, 60 post-Implant 1; Day 30, 60 post-Implant 2
Emotional Function of Pancreatic Cancer Participants	The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including emotional function), three symptom scales, a global health status score, and six single items. Emotional Function is assessed from 4 of the 30 questions (Questions 21-24), whose response score ranges on a 4 point scale. The score for role function is calculated based on the average score from these 4 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome.	Baseline; Day 30, 60 post-Implant 1; Day 30, 60 post-Implant 2
Cognitive Function of mCRC Participants	The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including cognitive function), three symptom scales, a global health status score, and six single items. Cognitive Function is assessed from 2 of the 30 questions (Question 20 and 25), whose response score ranges on a 4 point scale. The score for role function is calculated based on the average score from these 2 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome.	Baseline; Day 30, 60 post-Implant 1; Day 30, 60 post-Implant 2
Cognitive Function of Pancreatic Cancer Participants	The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including cognitive function), three symptom scales, a global health status score, and six single items. Cognitive Function is assessed from 2 of the 30 questions (Question 20 and 25), whose response score ranges on a 4 point scale. The score for role function is calculated based on the average score from these 2 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome.	Baseline; Day 30, 60 post-Implant 1; Day 30, 60 post-Implant 2
Social Function of mCRC Participants	The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including social function), three symptom scales, a global health status score, and six single items. Social Function is assessed from 2 of the 30 questions (Question 26 and 27), whose response score ranges on a 4 point scale. The score for role function is calculated based on the average score from these 2 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome.	Baseline; Day 30, 60 post-Implant 1; Day 30, 60 post-Implant 2
Social Function of Pancreatic Cancer Participants	The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including social function), three symptom scales, a global health status score, and six single items. Social Function is assessed from 2 of the 30 questions (Question 26 and 27), whose response score ranges on a 4 point scale. The score for role function is calculated based on the average score from these 2 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome.	Baseline; Day 30, 60 post-Implant 1; Day 30, 60 post-Implant 2
Pain Assessment of mCRC Participants	Participants were asked to rate their pain on a discrete scale (from 0 = "no pain" to 10 "worst pain imaginable, unbearable"). The worst pain at each time point was used in the analysis.	Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2
Pain Assessment of Pancreatic Cancer Participants	Participants were asked to rate their pain on a discrete scale (from 0 = "no pain" to 10 "worst pain imaginable, unbearable"). The worst pain at each time point was used in the analysis.	Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2

Collaborators and Investigators

• Sponsor: The Rogosin Institute
• Collaborators: Vital Systems Inc.
• Investigators: Principal Investigator: Thomas Fahey, III., MD, Weill Cornell Medical Center / New York-Presbyterian Hospital

Publications and helpful links

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.

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2010
• Primary Completion (Actual): April 16, 2016
• Study Completion (Actual): April 16, 2016

Study Registration Dates

• First Submitted: January 20, 2010
• First Submitted That Met QC Criteria: January 20, 2010
• First Posted (Estimate): January 21, 2010

Study Record Updates

• Last Update Posted (Actual): May 12, 2021
• Last Update Submitted That Met QC Criteria: April 23, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: biological; macrobead; mouse cells
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Adenocarcinoma
• Other Study ID Numbers: 0911010739

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No