Proton w/FOLFIRINOX-Losartan for Pancreatic Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Massachusetts General Hospital
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Theodore Sunki Hong, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01821729
First received: March 27, 2013
Last updated: April 10, 2014
Last verified: April 2014

March 27, 2013
April 10, 2014
July 2013
July 2015   (final data collection date for primary outcome measure)
Feasibility of combining FOLFIRINOX-Losartan [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To determine the feasibility of the combination of FOLIRINIOX-Losartan in patients with locally advanced unresectable pancreas cancer determining the proportion free of radiographic progression at the time of restaging and consideration of proton therapy after induction chemotherapy
Same as current
Complete list of historical versions of study NCT01821729 on ClinicalTrials.gov Archive Site
  • Progression-Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine the progression free survival of patients with locally advanced disease who receive FOLFIRINOX-Losartan and proton beam radiation therapy
  • Overall Survival for FOLFIRINOX + Proton Beam Radiation [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine overall survival in patients treated with preoperative FOLFIRINOX and proton beam radiation therapy
  • Overall Survival for FOLFIRINOX Without Proton Radiation [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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)
  • Determine Toxicity FOLFIRINOX-Losartan [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To determine the toxicity of FOLFIRINOX-Losartan in patients with locally advanced pancreatic disease
  • Determine Toxicity of FOLFIRINOX-Losartan and Proton Beam Radiation [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To determine the toxicity of FOLFIRINOX-Losartan and proton beam radiation in patients with locally advanced pancreatic cancer.
  • Rate of Downstaging [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine the rate of downstaging to surgical resection of FOLFIRINOX-Losartan followed by proton radiation in patients with locally advanced pancreatic cancer
  • Determine correlation of Somatic Gene Mutations and Outcome [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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
  • Determine Correlation Between Circulating Biomarkers and Outcome [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.
Same as current
Not Provided
Not Provided
 
Proton w/FOLFIRINOX-Losartan for Pancreatic Cancer
Phase II Feasibility Study of FOLFIRINOX-Losartan Followed by Accelerated Short Course Radiation Therapy With Proton Beam for Locally Advanced Pancreatic Cancer

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.

If you are willing to participate in this research study, you will be asked to undergo some screening tests and procedures to confirm that you are eligible. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if it turns out that you do not take part in the research study. If you have had some of these tests or procedures recently, they may or may not have to be repeated. These tests and procedures will include a medical history, routine physical exam, performance status, assessment of your tumor, routine blood tests, a blood sample to check your kidney function and a serum or urine pregnancy test if applicable. If these tests show that you are eligible to participate in the research study, you will begin the study treatment. If you do not meet the eligibility criteria, you will not be able to participate in this research study.

There are two phases to this study. Phase I involves FOLFIRINOX and Losartan. The treatment plant will begin with 8 cycles of FOLFIRINOX. Each cycle is 14 days, or 2 weeks long. FOLFIRINOX is comprised of four drugs: Oxaliplatin, irinotecan, fluorouracil and leucovorin. On Day 1 of each 14 day cycle, you will receive oxaliplatin via IV infusion over a period of 2 hours. Irinotecan will be administered via IV infusion on Day 1 of each cycle over a period of 90 minutes.

You will receive fluorouracil (5FU) on Day 1 of each cycle via IV infusion over a period of 2-4 minutes. You will then be fitted with an ambulatory infusion pump that will be delivered continuously over 46-48 hours.

In addition to these infusions, FOLFIRINOX will always be administered along with a two hours IV infusion of leucovorin, a drug composed of reduced folic acid, which helps enhance the effects of chemotherapy. You will be give leucovorin through a vein in your arm for 2 hours a day on Day 1 of each cycle.

You will also receive an injection of Neulasta after each FOLFIRINOX treatment. Neulasta is used to reduce the chance of infection from chemotherapy by boosting your white blood cell count. It will be administered 24-48 hours after your FOLFIRINOX infusion (on Day 3 or 4).

You will take one dose of Losartan by mouth every day during Phase I for all 8 cycles of FOLFIRINOX. If the dose of Losartan given to you during the first week does not give you any serious side effects, your dose will be increased once for the remainder of Phase I. We have provided a drug diary for you with instructions on how to take this tablet and what to do incase of any missed or vomited doses. We will monitor your response to treatment with a chest/abdominal CT after four cycles of FOLFIRINOX therapy (8 weeks).

Phase II involves Restaging/Proton Beam Radiation Therapy and Capecitabine. At this time your study doctor will assess for any progress in your cancer after the FOLFIRINOX + Losartan treatment again via CT scan. If your cancer has progressed, you will be removed from the study and continue with standard of care treatment. If it has not progressed, you will continue to the proton radiation therapy and capecitabine phase of the study.

During this phase you will receive proton beam radiation therapy at the Francis H. Burr Proton Therapy center for 1 week, Monday through Friday. Each visit is expected to take 30-45 minutes.

During the week of proton radiation therapy and for the week after, you will take capecitabine by mouth on Monday through Friday, for a total of ten days. You will be given a drug diary with instructions on how to take capecitabine and what to do in case of a missed or vomited dose.

You will receive the following tests and procedures at various time points during both portions of the study. These tests and procedures will include: routine blood tests, blood sample to check kidney function, CA19-9 and CEA blood tests, Chest CT/Abdominal-Pelvic CT, assessment for side effects, vital signs, performance status, routine physical exam and blood pressure monitoring.

After the final dose of study drug you will come into the clinic for follow-up visits for some assessments every 3 months until your cancer progresses. You will undergo the following tests: routine physical exam, vital signs, performance status, routine blood tests, assessment for side effects. In addition you are required to have a chest and abdominal/pelvic CT every 6 months for the first two years, and yearly for years 3-5. We would like to keep track of your medical condition for the rest of your life. We would like to do this by calling you on the telephone once a year to see how you are doing. Keeping in touch with you and checking on your condition every year helps us look at the long term effects of the research study.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Pancreatic Cancer
  • Drug: FOLFIRINOX
    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
Experimental: Experimental Arm
FOLFIRINOX, Losartan, Proton Beam Radiation Therapy
Interventions:
  • Drug: FOLFIRINOX
  • Drug: Losartan
  • Radiation: Proton Beam Radiation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
32
Not Provided
July 2015   (final data collection date for primary outcome measure)

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 (carcinoma in-situ is 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
Both
18 Years and older
No
Contact: Theodore Hong, MD 6177267559 tshong1@partners.org
United States
 
NCT01821729
13-051
Yes
Theodore Sunki Hong, Massachusetts General Hospital
Massachusetts General Hospital
National Cancer Institute (NCI)
Principal Investigator: Theodore Hong, MD Massachusetts General Hospital
Massachusetts General Hospital
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP