Proton w/FOLFIRINOX-Losartan for Pancreatic Cancer
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Cancer, Cancer, Pancreatic Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 1/25/2019 |
| Start Date: | July 2013 |
| End Date: | July 2019 |
Phase II Feasibility Study of FOLFIRINOX-Losartan Followed by Accelerated Short Course Radiation Therapy With Capecitabine 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.
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.
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.
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
We found this trial at
1
site
185 Cambridge Street
Boston, Massachusetts 02114
Boston, Massachusetts 02114
617-724-5200
Principal Investigator: Theodore Hong, MD
Phone: 617-726-7559
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