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

Study Overview
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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

Official Title
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A Phase IIb, Nonrandomized, Open-Label Trial With Mouse Renal Adenocarcinoma (RENCA) Cell Containing Agarose-Agarose Macrobeads Compared With Best Supportive Care in Patients With Treatment-Resistant, Metastatic Colorectal Carcinoma

Conditions
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Colorectal Cancers

Intervention / Treatment
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* Biological: RENCA macrobeads


Participation Criteria
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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: 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 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: International Normalized Ratio (INR) ≤1.5 or between 2 and 3 if the patient is receiving anticoagulation 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Macrobead Implantation Arm<br>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<br> <br> * Other names: macrobead;|
| No Intervention: Best Supportive Care Arm<br>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 | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Performance Status (ECOG Score) | 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. 1: 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). 2: Ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50% of waking hours. 3: Capable of only limited self-care, confined to bed or chair 50% or more of waking hours. 4: Completely disabled, cannot carry on any self-care, totally confined to bed or chair. 5: Death | Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2 | 
| Activities of Daily Living (KPS Score) | 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 | 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 | TThe 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 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2 | 
| Role Function | 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 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2 | 
| Emotional Function | 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 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2 | 
| Cognitive Function | 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 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2 | 
| Social Function | 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 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2 | 
| Pain Assessment | Participants were asked to rate their pain on a discrete scale (from 0 = no pain to 100 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colon, colorectal, rectal, cancer, macrobead, stage IV, metastatic, biological, mouse cells, new york, new jersey, clinical research