Proton w/FOLFIRINOX-Losartan for Pancreatic Cancer
Condition: Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: FOLFIRINOX; Losartan; Proton Beam Radiation
Intervention description: Oxaliplatin via IV on Day 1 over 2 hours; Irinotecan via IV on Day 1 over 90 minutes, 5FU via IV on Day 1 over 2-4 minutes; Taken orally every day during Phase I for all 8 cycles; 30-45 minutes per day, daily Monday-Friday
Intervention MeSH terms: Leucovorin; Fluorouracil; Oxaliplatin; Folfirinox; Losartan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Locally Advanced

Summary:

      This is a Phase II clinical trial, which tests the safety and effectiveness of an
      investigational combination of drugs to learn whether the combination of drugs works in
      treating a specific cancer. "Investigational" means that the combination of drugs is being
      studied. It also means that the FDA has not yet approved it for your type of cancer. Proton
      beam radiation therapy is an FDA approved radiation delivery system.

      Conventional radiation therapy uses photons to treat cancer before patients undergo surgery
      to remove the tumor. In this study we are using radiation with protons, which spares
      surrounding tissue and organs from radiation. Proton radiation delivers radiation to the area
      requiring radiation with no dose beyond the treatment area. This may reduce side effects that
      patients would normally experience with conventional radiation therapy.

      Researchers in the laboratory have discovered pathways inside cancer cells which contribute
      to the growth and survival of tumors. The FOLFIRINOX chemotherapy regimen is a combination of
      the drugs 5-fluorouracil, leucovorin and oxaliplatin. These chemotherapy drugs, along with
      the chemotherapy drug capecitabine, work by blocking these pathways and thereby preventing
      tumor growth. Capecitabine is FDA approved to be used alone or with other drugs to treat
      other types of advanced cancer, but not pancreatic cancer. In past research studies,
      FOLFIRINOX followed by radiation therapy with capecitabine has been identified as the most
      effective and active chemotherapy for patients with cancer that is spreading, and this is why
      we are using it to treat your type of cancer.

      Losartan is classified as an angiotensin-receptor blocker (ARB), and is FDA approved for use
      in people with high blood pressure. Recent studies in people with different types of cancer,
      including pancreatic cancer, have shown that combining chemotherapy drugs with an ARB can
      help reduce/stop tumor growth more effectively than chemotherapy alone. Losartan has been
      used in previous research studies, and information from those research studies suggests that
      this drug in combination with FOLFIRINOX and capecitabine may be better at treating your type
      of cancer.

      In this research study, we seek to determine whether combining FOLFIRINOX with Losartan
      before proton radiation therapy will be more efficient at controlling the growth of or
      shrinking your tumor than just FOLFIRINOX alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Cytologic or histologic proof pancreatic ductal carcinoma

          -  Locally advanced, unresectable disease

          -  Life expectancy of at least 3 months

        Exclusion Criteria:

          -  Evidence of metastatic disease

          -  Pregnant or breastfeeding

          -  Serious concomitant systemic disorders incompatible with the study

          -  Already treated on ACE or ARB therapy for hypertension or renal protection at the time
             of enrollment

          -  Baseline hypotension

          -  Prior chemotherapy, radiation therapy, or biologic therapy for treatment of pancreatic
             tumor

          -  Treatment for other invasive carcinomas within the last 5 years who are greater than
             5% risk of recurrence at the time of eligibility screening (carcinoma in-situ and
             basal cell carcinoma/squamous cell carcinoma of the skin are allowed)

          -  Other serious uncontrolled medical conditions

          -  Lack of physical integrity of the upper gastrointestinal tract or malabsorption
             syndrome

          -  Known, existing coagulopathy

          -  Prior systemic fluoropyrimidine therapy

          -  Participation in any investigational drug study within 4 weeks preceding the start of
             study treatment

          -  History of uncontrolled seizures, central nervous system disorders or psychiatric
             disability judged by the investigator to be clinically significant, precluding
             informed consent or interfering with compliance or oral drug intake

          -  Major surgery, excluding laparoscopy, within 4 weeks of the start of study treatment

          -  Taking cimetidine

          -  Receiving other study agents

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to 5-fluorouracil, irinotecan, oxaliplatin or losartan