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

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:
• 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)
• 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:
• an international normalized ratio (INR) ≤ 1.5
• a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN, unless on anti-coagulant therapy
• 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:
• ANC 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:
• INR > 1.5
• 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.