Open-Label Phase 2 Efficacy Trial of Cancer Macrobeads in Patients With Treatment-Resistant Pancreatic/Colorectal Cancer
Condition: Pancreatic Adenocarcinoma Non-resectable; Pancreatic Adenocarcinoma Metastatic; Colorectal Cancer Metastatic
MeSH terms: Colorectal Neoplasms; Adenocarcinoma
Intervention: RENCA macrobeads
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 58.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: macrobead; biological; mouse cells

Summary:

      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.
    

Eligibility criteria:

        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.