Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Digestive System Diseases

Rare Diseases

Adenocarcinoma

Carcinoma, Renal Cell

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Renal Cell Carcinoma

Papillary Renal Cell Carcinoma

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

RENCA macrobeads

Thomas Fahey, III., MD

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.

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

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

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.

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.

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.

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.

Erythrocyte sedimentation rate (ESR) is one of three inflammatory markers assessed during this study. ESR was assessed as a marker of systemic inflammatory processes.

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.

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

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

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.

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.

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.

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.

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.

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.

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.

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.

The secondary efficacy objective was to evaluate overall survival calculated using the time from first RENCA macrobead implantation to death from any cause.

The secondary efficacy objective was to evaluate overall survival calculated using the time from Stage IV disease diagnosis to death from any cause.

Vital Systems Inc.

The Rogosin Institute

The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, serious adverse events, AEs \> Grade 2, laboratory values of special interest and subject deaths.

Metastatic colorectal cancer (mCRC) patients who underwent at least 1 (and 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.

Metastatic Colorectal Cancer (mCRC) Participants

Pancreatic cancer patients who underwent at least 1 (and up to 3) implantations of RENCA macrobeads (no less than 3 months apart), at a dosage level of 8 RENCA macrobeads per kilogram of body weight.

Pancreatic Cancer Participants

Pancreatic cancer patients 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.

RENCA Macrobeads.

Pancreatic Cancer

Metastatic colorectal cancer (mCRC) 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.

RENCA macrobeads

Metastatic Colorectal Cancer

Total

Age, Continuous

Sex: Female, Male

White

Black

Hispanic

Asian

Native American

Other

Race/Ethnicity, Customized

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.

Betty-Jane Sloan, Clinical Research Manager

Participants who received at least one RENCA macrobead implant.

Overall Survival - Based on Most Recent Scan

Overall Survival - Based on 1st Implant

mCRC participants with stable disease based on imaging results \[Tumor measurements/SUV max\].

Stable

mCRC participants with decreased/necrosis observed based on imaging results \[Tumor measurements/SUV max\].

Decreased/Necrosis

mCRC participants with increased SUVmax, tumor measurement based on imaging results.

Increased

mCRC participants who had received at least one macrobead implant and for whom baseline PET-CT scan and day 90 post-Implant 1 PET-CT scan data were available. n=26 subjects; 77 lesions evaluated. No formal analysis was performed on the pancreatic cancer cohort as a meaningful analysis was limited based on the small group size with baseline and day 90 scans.

Necrosis Comparison of Tumors Using PET-CT Scan

Participants with mCRC whose tumor marker response was greater than or equal to 20% decrease from baseline in CEA only \[up to and including day 90 after the first implant).

mCRC: CEA Only

Participants with mCRC whose tumor marker response was greater than or equal to 20% decrease from baseline in CA 19-9 only \[up to and including day 90 after the first implant).

mCRC CA 19-9 Only

Participants with mCRC whose tumor marker response was greater than or equal to 20% decrease from baseline in both CEA and CA 19-9 \[up to and including day 90 after the first implant).

mCRC: Both CEA and CA 19-9

Participants with mCRC whose tumor marker response (serum level of CEA and/or CA 19-9) did not decrease by greater than or equal to 20% of baseline value.

mCRC: Non-responder

Participants with mCRC receiving at least one RENCA macrobead implantation.

Tumor Marker Response of mCRC Participants

Participants with pancreatic cancer whose tumor marker response was greater than or equal to 20% decrease from baseline in CEA only \[up to and including day 90 after the first implant).

Pancreatic Cancer: CEA Only

Participants with pancreatic cancer whose tumor marker response was greater than or equal to 20% decrease from baseline in CA 19-9 only \[up to and including day 90 after the first implant).

Pancreatic Cancer: CA 19-9 Only

Participants with pancreatic cancer whose tumor marker response was greater than or equal to 20% decrease from baseline in both CEA and CA 19-9 \[up to and including day 90 after the first implant).

Pancreatic Cancer: Both CEA and CA 19-9

Participants with pancreatic cancer whose tumor marker response (serum level of CEA and/or CA 19-9) did not decrease by greater than or equal to 20% of baseline value.

Pancreatic Cancer: Non-responder

Participants with pancreatic cancer receiving at least one RENCA macrobead implantation.

Tumor Marker Response of Pancreatic Cancer Participants

CRP levels at baseline, prior to first implantation.

Implant 1: Day 0

CRP levels at day 14 after first implantation.

Implant 1: Day 14

CRP levels at day 30 after first implantation.

Implant 1: Day 30

CRP levels at day 60 after first implantation.

Implant 1: Day 60

CRP levels at day 0 of second implantation (day 90 following first implantation).

Implant 2: Day 0

CRP levels at day 14 after second implantation.

Implant 2: Day 14

CRP levels at day 30 after second implantation.

Implant 2: Day 30

CRP levels at day 60 after second implantation.

Implant 2: Day 60

Implant 1 (Days 0-60): Participants with mCRC who had received at least 1 RENCA macrobead implantation and were screened as indicated; Implant 2 (Days 0-60): Participants with mCRC who had received at least 2 RENCA macrobead implantations and were screened as indicated. In some cases, participants may not have had all assessments conducted as scheduled. In those incidents, the number of participants analyzed has been adjusted to include only those participants for which data was available.

C-reactive Protein Levels in mCRC Participants

Implant 1 (Days 0-60): Pancreatic cancer participants who had received at least 1 implant and were screened as indicated; Implant 2 (Days 0-60): Pancreatic cancer participants who had received at least 2 RENCA macrobead implantations and were screened as indicated. In some cases, participants may not have had all assessments conducted as scheduled. In those incidents, the number of participants analyzed has been adjusted to include only those participants for which data was available.

C-Reactive Protein Levels in Pancreatic Cancer Participants

ESR at baseline, prior to first implantation.

ESR at day 0 of second implantation (day 90 following first implantation).

Erythrocyte Sedimentation Rate in mCRC Participants

Erythrocyte Sedimentation Rate in Pancreatic Cancer Participants

CA 125 levels at baseline, prior to first implantation.

CA 125 levels at day 14 after first implantation.

CA 125 levels at day 30 after first implantation.

CA 125 levels at day 60 after first implantation.

CA 125 levels at day 0 of second implantation (day 90 following first implantation).

CA 125 levels at day 14 after second implantation.

CA 125 levels at day 30 after second implantation.

CA 125 levels at day 60 after second implantation.

Cancer Antigen 125 Levels in mCRC Participants

Cancer Antigen 125 Levels in Pancreatic Cancer Participants

ECOG score at pre-screening for first implantation.

ECOG score at day 14 after first implantation.

ECOG score at day 30 after first implantation.

ECOG score at day 60 after first implantation.

ECOG score at pre-screening for second implantation (day 90 following first implantation).

ECOG score at day 14 after second implantation.

ECOG score at day 30 after second implantation.

ECOG score at day 60 after second implantation.

Implant (day 0 to day 60): Participants with mCRC who received at least one RENCA macrobead implantation; Implant 2 (day 0 to day 60): Participants who received at least two RENCA macrobead implantations.

Performance Status (ECOG Score) of mCRC Participants

Implant 1 (Days 0-60): Pancreatic cancer participants who had received at least 1 macrobead implantation and were screened as indicated; Implant 2 (Days 0-60): Pancreatic cancer participants who had received at least 2 macrobead implantations and were screened as indicated. In some cases, participants may not have had all assessments conducted as scheduled. In those incidents, the number of participants analyzed has been adjusted to include only those participants for which data was available.

Performance Status (ECOG Score) of Pancreatic Cancer Participants

KPS score at pre-screening for first implantation.

KPS score at day 14 after first implantation.

KPS score at day 30 after first implantation.

KPS score at day 60 after first implantation.

KPS score at pre-screening for second implantation (day 90 following first implantation).

KPS score at day 14 after second implantation.

Activities of Daily Living (KPS Score) of mCRC Participants

KPS score at day 30 after second implantation.

KPS score at day 60 after second implantation.

Activities of Daily Living (KPS Score) for Pancreatic Cancer Participants

Global health status score at pre-screening for first implantation.

Global health status score at day 14 after first implantation.

Global health status score at day 30 after first implantation.

Global health status score at day 60 after first implantation.

Global health status score at pre-screening for second implantation (day 90 following first implantation).

Global health status score at day 14 after second implantation.

Global health status score at day 30 after second implantation.

Global health status score at day 60 after second implantation.

Global Health Status of mCRC Participants

Global Health Status of Pancreatic Cancer Participants

EORTC/Physical functioning score at pre-screening for first implantation.

EORTC/Physical functioning score at day 30 after first implantation.

EORTC/Physical functioning score at day 60 after first implantation.

EORTC/Physical functioning score at pre-screening for second implantation (day 90 following first implantation).

EORTC/Physical functioning score at day 30 after second implantation.

EORTC/Physical functioning score at day 60 after second implantation.

Implant 1 (Day 0 to Day 60): Participants with mCRC who had received at least 1 RENCA macrobead implantation; Implant 2 (Day 0 to Day 60): Participants with mCRC who had received at least 2 RENCA macrobead implantations.

Physical Function of mCRC Participants

Implant 1 (Day 0 to Day 60): Pancreatic cancer participants who had received at least 1 macrobead implantation; Implant 2 (Day 0 to Day 60): Pancreatic cancer participants who had received at least 2 macrobead implantations.

Physical Function of Pancreatic Cancer Participants

EORTC/Role functioning score at pre-screening for first implantation.

EORTC/Role functioning score at day 30 after first implantation.

EORTC/Role functioning score at day 60 after first implantation.

EORTC/Role functioning score at pre-screening for second implantation (day 90 following first implantation).

EORTC/Role functioning score at day 30 after second implantation.

EORTC/Role functioning score at day 60 after second implantation.

Role Function of mCRC Participants

Implant 1 (Day 0 to Day 60): Participants with pancreatic cancer who had received at least 1 RENCA macrobead implantation; Implant 2 (Day 0 to Day 60): Participants with pancreatic cancer who had received at least 2 RENCA macrobead implantations.

Role Function of Pancreatic Cancer Participants

EORTC/Emotional functioning score at pre-screening for first implantation.

EORTC/Emotional functioning score at day 30 after first implantation.

EORTC/Emotional functioning score at pre-screening for second implantation (day 90 following first implantation).

EORTC/Emotional functioning score at day 30 after second implantation.

EORTC/Emotional functioning score at day 60 after second implantation.

Emotional Function of mCRC Participants

Emotional Function of Pancreatic Cancer Participants

EORTC/Cognitive functioning score at pre-screening for first implantation.

EORTC/Cognitive functioning score at day 30 after first implantation.

EORTC/Cognitive functioning score at day 60 after first implantation.

EORTC/Cognitive functioning score at pre-screening for second implantation (day 90 following first implantation).

EORTC/Cognitive functioning score at day 30 after second implantation.

EORTC/Cognitive functioning score at day 60 after second implantation.

Cognitive Function of mCRC Participants

Cognitive Function of Pancreatic Cancer Participants

EORTC/Social functioning score at pre-screening for first implantation.

EORTC/Social functioning score at day 30 after first implantation.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Open-Label Phase 2 Efficacy Trial of Cancer Macrobeads in Patients With Treatment-Resistant Pancreatic/Colorectal Cancer	NCT01053013	Pancreatic Aden... Pancreatic Aden... Colorectal Canc...	RENCA macrobead...	18 Years -	The Rogosin Institute
Open-Label Phase 2 Efficacy Trial of Cancer Macrobeads in Patients With Treatment-Resistant Pancreatic/Colorectal Cancer	NCT01053013	Pancreatic Aden... Pancreatic Aden... Colorectal Canc...	RENCA macrobead...	18 Years -	The Rogosin Institute

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