Nonrandomized, Open-Label Phase IIb Efficacy Trial of Cancer Macrobeads Compared With Best Supportive Care in Patients With Treatment-Resistant Colorectal Cancer

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 small beads
that contain mouse cancer cells from a mouse kidney cancer cell line. The cells in the beads
produce substances that have been shown to slow or stop the growth of tumors in experimental
animals, veterinary patients, and 37 humans with colorectal cancers in a Phase 1 and 2
safety trials.

Eligibility Criteria

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 is resistant to available treatment
options

- Radiographically documented 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 withstand general anesthesia.

- Able to provide written informed consent.

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 be receiving 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.

- Agrees to contraceptive use while on study if sexually active

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

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.

Principal Investigator

Stephen K Williamson, MD

Study Contact

ctnursenav@kumc.edu, 913-945-7552

Estimated Completion Date

Friday, December 1, 2017

ClinicalTrials.gov #

NCT02046174
06/02/2015