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Proton w/FOLFIRINOX-Losartan for Pancreatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01821729
Recruitment Status : Unknown
Verified September 2020 by Theodore Sunki Hong, Massachusetts General Hospital.
Recruitment status was:  Active, not recruiting
First Posted : April 1, 2013
Results First Posted : September 17, 2019
Last Update Posted : September 25, 2020
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Theodore Sunki Hong, Massachusetts General Hospital

Brief 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.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Drug: FOLFIRINOX Drug: Losartan Radiation: Proton Beam Radiation Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Feasibility Study of FOLFIRINOX-Losartan Followed by Accelerated Short Course Radiation Therapy With Capecitabine for Locally Advanced Pancreatic Cancer
Study Start Date : July 2013
Actual Primary Completion Date : July 2018
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Experimental Arm
FOLFIRINOX, Losartan, Proton Beam Radiation Therapy
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
Other Names:
  • 5-Fluorouracil
  • 5FU
  • Leucovorin
  • Oxaliplatin

Drug: Losartan
Taken orally every day during Phase I for all 8 cycles

Radiation: Proton Beam Radiation
30-45 minutes per day, daily Monday-Friday

Primary Outcome Measures :
  1. Number of Participants With R0 Resection [ Time Frame: At the time of surgery (approximately 4 months after the start of treatment) ]
    The number of participants that received treatment with proton radiation along with FOLFIRINOX-Losartan and then subsequently underwent attempted surgery and achieved R0 resection. R0 resection means that no cancer cells were seen microscopically at the resection margin.

Secondary Outcome Measures :
  1. Progression-Free Survival [ Time Frame: From the start of treatment until death or progression, median duration of 17.5 months ]

    To determine the progression free survival of patients with locally advanced disease who receive FOLFIRINOX-Losartan and proton beam radiation therapy. Disease progression was assessed using Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

    Progressive disease (PD): At least a 20% increase in the sum of the longest diameter (LD) of target lesion, taking as reference the smal lest sum LD recorded since the treatment started or the appearance of one or more new lesions (new lesions must be > slice thickness).

  2. Overall Survival for FOLFIRINOX + Proton Beam Radiation [ Time Frame: 2 years ]
    To determine overall survival in patients treated with preoperative FOLFIRINOX and proton beam radiation therapy

  3. Overall Survival for FOLFIRINOX Without Proton Radiation [ Time Frame: 2 years ]
    To determine the overall survival of patients with locally advanced disease who receive FOLFIRINOX-Losartan without proton radiation (i.e. patients who demonstrate progression at restaging)

  4. Determine Toxicity FOLFIRINOX-Losartan [ Time Frame: 2 years ]
    To determine the toxicity of FOLFIRINOX-Losartan in patients with locally advanced pancreatic disease

  5. Determine Toxicity of FOLFIRINOX-Losartan and Proton Beam Radiation [ Time Frame: 2 years ]
    To determine the toxicity of FOLFIRINOX-Losartan and proton beam radiation in patients with locally advanced pancreatic cancer.

  6. Rate of Downstaging [ Time Frame: 2 years ]
    To determine the rate of downstaging to surgical resection of FOLFIRINOX-Losartan followed by proton radiation in patients with locally advanced pancreatic cancer

  7. Determine Correlation of Somatic Gene Mutations and Outcome [ Time Frame: 2 years ]
    To determine the correlation between a panel of somatic genetic mutations (SNaPSHOT) and outcome in locally advanced pancreatic cancer treated with FOLFIRINOX-Losartan +/- proton beam radiation/capecitabine

  8. Determine Correlation Between Circulating Biomarkers and Outcome [ Time Frame: 2 years ]
    To determine the correlation between circulating biomarkers of TGF-B1 downregulation, including circulating Collagen I levels, and outcome in locally advanced pancreatic cancer treated with FOLFIRINOX-Losartan +/- proton beam radiation/capecitabine.

  9. Describe Quality of Life, Symptom Burden and Mood [ Time Frame: 2 years ]
    Describe quality of life, symptom burden and mood in the study population

  10. To Measure Utilization of Health Services [ Time Frame: 2 years ]
    To measure utilization of health services (ER, hospital and ICU visits) in the study population

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01821729

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United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
National Cancer Institute (NCI)
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Principal Investigator: Theodore Hong, MD Massachusetts General Hospital
  Study Documents (Full-Text)

Documents provided by Theodore Sunki Hong, Massachusetts General Hospital:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Theodore Sunki Hong, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01821729    
Other Study ID Numbers: 13-051
First Posted: April 1, 2013    Key Record Dates
Results First Posted: September 17, 2019
Last Update Posted: September 25, 2020
Last Verified: September 2020
Keywords provided by Theodore Sunki Hong, Massachusetts General Hospital:
Locally Advanced
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protective Agents
Vitamin B Complex
Anti-Arrhythmia Agents
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists