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Gastrointestinal Agents

Irinotecan

Gemcitabine

Fluorouracil

Oxaliplatin

Folfirinox

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SYSTEMIC PHASE: Chemotherapy with Oxaliplatin followed by Irinotecan followed by 5-FU. m FOLFIRINOX - oxaliplatin 75 mg/m2 d1 + irinotecan 150 mg/m2 d1 + 5-FUl 2,000 mg/m2 46h continuous infusion, every other week for 6 cycles (12 weeks).

CHEMORADIATION PHASE: This phase will start at least 2 weeks, but no more than 6 weeks after completion of the last cycle of mFOLFIRINOX. Chemoradiation with Gemcitabine: 350 mg/m2 IV over 35 minutes every week for 5 doses beginning day 1 (days 1, 8, 15, 22, 29)

Radiation: External beam radiation therapy will be delivered 5 days/week +/- 2 days over 5.5 weeks with 18-MeV photons. 3D conformal RT, a total dose of 50.4 Gy prescribed to the 95% isodose at 1.8 Gy/fraction (28 fractions) to the GTV + 1.5 cm margin.

SURGERY- At least 4-6 weeks after last dose of Gemcitabine, if no local progression or distant metastasis. Patients whose scans show unequivocal local or distant progression are not candidates for surgery.

75 mg/m2 by vein on Day 1 of weeks 1, 3, 5, 7, 9 and 11 for 12 weeks.

150 mg/m2 by vein on Day 1 of weeks 1, 3, 5, 7, 9 and 11 for 12 weeks.

2000 mg/m2 by vein over 46 hour continuous infusion, on Days 1 - 2 during weeks 1, 3, 5, 7, 9 and 11 for 12 weeks.

5-FU

350 mg/m2 by vein every week for 5 doses beginning Day 1 (days 1, 8, 15, 22, 29).

External beam radiation therapy delivered 5 days/week +/- 2 days over 5.5 weeks with 18-MeV photons. 3D conformal RT, a total dose of 50.4 Gy 1.8 Gy/fraction (28 fractions).

Radiation Therapy

Gauri Varadhachary, MD, MBBS

The goal of this clinical research study is to learn if a chemotherapy combination called modified Folfirinox (or mFolfirinox), followed by a combination of gemcitabine and radiation therapy, followed by surgery, can help to control pancreatic cancer. The safety of this treatment will also be studied.

mFolfirinox consists of 5-FU, oxaliplatin, and irinotecan. These 3 drugs, along with gemcitabine, are each designed to block the growth of cancer cells, which may lead to cancer cell death.

Study Drug Administration:

You will receive up to 3 phases of study therapy: the systemic chemotherapy phase, the chemoradiation phase, and surgery, if possible.

During the systemic chemotherapy phase, you will receive mFolfirinox 1 time every 2 weeks (Weeks 1, 3, 5, 7, 9 and 11) for 12 weeks. You will receive oxaliplatin by vein over a 2-hour period. After receiving oxaliplatin, you will receive irinotecan by vein over a 90-minute period. After receiving irinotecan, you will then receive 5-FU through a portable pump for the next 46 hours. You will take the portable pump home with you and will receive instructions on how to use it.

You will begin receiving chemoradiation within 6 weeks after you have finished receiving the Week 11 dose of mFolfirinox. However, you will not begin receiving it until you have recovered from side effects of the chemotherapy.

During the chemoradiation phase, you will receive gemcitabine over about 35 minutes 1 time each week for 5 weeks. You will also receive radiation therapy 5 days a week (Monday through Friday) for 5 1/2 weeks (a total of 28 treatments). If you miss any of the days of radiation, they will be made up at the end of treatment so that you will receive the full amount of radiation. You will be given a separate consent form that explains the radiation procedure and the risks it may present.

After the chemoradiation phase, you will not receive any treatment for 4-6 weeks so your body can recover. If after this time the disease has not gotten worse or spread to other parts of the body, you will have surgery to try to remove the tumor. You will be given a separate consent form for the surgery that describes how it is performed and its risks.

If the disease has gotten worse or spread to other parts of the body, you will not be able to have surgery. The study doctor will discuss other therapy options with you.

Study Visits:

At Weeks 1, 3, 5, 7, 9, and 11 of the systemic chemotherapy phase:

* You will have a physical exam, including measurement of your weight and vital signs (blood pressure and heart rate).
* Blood (about 3 tablespoons) will be drawn for routine tests.

Within 4 weeks before beginning the chemoradiation phase:

* You will have CT or MRI scans to check the status of the disease.
* Blood (about 1 tablespoon) will be drawn for tumor marker testing.

At Weeks 1, 2, 3, 4, 5, and 6 of the chemoradiation phase:

* You will have a physical exam, including measurement of your weight and vital signs.
* Blood (about 2-3 tablespoons) will be collected for routine tests. At Week 6, an additional 2 teaspoons of blood will be drawn for CTC testing.

About 4 to 6 weeks after you complete the chemoradiation phase:

* Blood (about 1 tablespoon) will be drawn for tumor marker testing.
* You will have CT or MRI scans to check the status of the disease.

If you are eligible to have surgery after the chemoradiation phase, the following tests and procedures will also be performed:

* Blood (about 4 teaspoons total) will be drawn within 2 weeks before surgery for CTC testing. Blood will also be collected during surgery, if the surgeon thinks it is safe and feasible.
* Tumor tissue collected during a previous procedure will be used for biomarker testing. An additional sample of tumor tissue will be collected from the tissue removed during surgery and used for biomarker testing. Biomarkers are found in the blood/tissue and may be related to your reaction to the study drug.

Length of Study:

You will receive study treatment over the course of up to 30 weeks. You will be taken off study if the disease gets worse, the study doctor thinks it is in your best interest, or if you do not follow the study directions.

You may choose to stop receiving the study treatment at any time. If you choose to stop, you should tell the study doctor or a member of the staff right away. They will make sure that proper procedures are followed and a final visit will be scheduled for your safety.

Follow-up:

Blood (about 2 teaspoons) will be collected for CTC testing 2-3 months after your surgery, if you were one of the first 30 participants enrolled in the study.

You will have a CT or MRI scan of the abdomen and pelvis every 4 months for 2 years to check the status of the disease.

This is an investigational study. 5-FU, oxaliplatin, irinotecan, and gemcitabine are each FDA approved and commercially available to treat different types of cancer:

* 5-FU: pancreatic, gastric, breast, colon/rectum, and skin cancer (basal cell carcinoma)
* Oxaliplatin: colon and rectal cancer
* Irinotecan: colorectal cancer
* Gemcitabine: pancreatic, lung, ovarian, and breast cancer.

The use of these 4 drugs together and in combination with radiation therapy for the treatment of pancreatic cancer is investigational.

Up to 33 patients will be enrolled in this study. All will be enrolled at MD Anderson.

Preoperative Folfirinox, Radiation Therapy for Resectable Adenocarcinoma of the Pancreas

A Phase II Study of Preoperative Systemic Chemotherapy (Modified FOLFIRINOX) Followed by Radiation Therapy for Patients With High Risk Resectable and Borderline Resectable Adenocarcinoma of the Pancreas

Patients with borderline resectable treated with preoperative modified FOLFIRINOX chemotherapy, followed by gemcitabine-based chemoradiation therapy. At least 4- 6 weeks after the last dose of gemcitabine if there is no local progression or distant metastasis, patients were scheduled for surgery.

The specimen was designated R0 if no tumor cells were identified at any of the resection margins.

Disease free survival (DFS) was defined as the time interval from the date of surgery to the date of disease recurrence or death or the date of a participant was last known to be alive without disease recurrence.

Tumor tissue collected pre-therapy and post-therapy for surgically resected patients was assessed for SMAD4 status and classified as either present or absent based on immunohistochemistry evaluation.

Overall survival (OS) was defined as the time interval from the date of diagnosis to the date of death due to any cause or the date a patient was last known to be alive. Estimated by using the Kaplan-Meier method.

M.D. Anderson Cancer Center

Toxicity was continuously monitored throughout the study, which includes grade 4 hematological toxicity and grade 3 or higher non-hematological toxicity.

Oxalipaltin 75 mg/m2 IV on day 1, irinotecan 150 mg/m2 IV on day 1, 5-fluorouracil 2,000 mg/m2 IV 46 hours continuous infusion, every other week for 6 cycles (12 weeks).

Systemin Phase: mFOLFIRINOX

Gemcitabine 350 mg/m2 IV weekly for 5 doses beginning day 1. External beam radiation therapy 5 days/week, a total dose of 50.4 Gy.

Chemoradiation Phase: Radiation With Gemcitabine

At least 4-6 weeks after the last dose of gemcitabine if there is no local progression or distant metastasis

Surgery

Oxaliplatin at 75 mg/m2 IV on day 1, Irinotecan at 150 mg/m2 IV on day 1, 5 fluorouracil at 2000 mg/m2 IV 46 hour continuous infusion on day 1 - 2, every other week for 6 cycles (12 weeks)

Systemic Phase: mFOLFIRINOX

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

A total of 34 participants enrolled in study 1 participant withdrew consent prior to receiving treatment.

Dr. Gauri R Varadhachary,Professor, GI Medical Oncology

At least 4 - 6 weeks after the last dose of Gemcitabine if there is no local progression or distant metastasis.

Number of Participants With Resectability Rate

Number of Participants With R0 Margin Resection

Oxalipaltin + irinotecan + 5-fluorouracil, every other week for 6 cycles (12 weeks) followed by gemcitabine weekly for 5 doses with radiation therapy 5 days/week. Then surgery at least 4-6 weeks after the last dose of gemcitabine if no local progression or distant metastasis.

All Phases

Disease Free Survival (DFS)

SMAD4 positive before surgery

SMAD4 positive after surgery

Number of Participants That Were SMAD4 Positive Before and After Surgery

All Phases(Systematic,Chemoradiation w/ Gemcitabine & Surgery)

Overall Survival

Local recurrence

Distant recurrence

Number of Participants With Local and Distant Failure

Present

Absent

Number of Participants Correlative Studies Including DPC4 (SMAD4) Staining and Circulating Tumor Cells (CTC) Pre-Surgery

Number of Participants Correlative Studies Including DPC4 (SMAD4) Staining and Circulating Tumor Cells (CTC) Post-Surgery

Systemic: Oxaliplatin at 75 mg/m2 IV on day 1, Irinotecan at 150 mg/m2 IV on day 1, 5 fluorouracil at 2000 mg/m2 IV 46 hour continuous infusion on day 1 - 2, every other week for 6 cycles (12 weeks).

Chemo: Gemcitabine at 350 mg/m2 IV weekly for 5 doses beginning day 1. External beam radiation therapy delivered 5 days/week, a total dose of 50.4 Gy.

Surgery: At least 4 - 6 weeks after the last dose of Gemcitabine if there is no local progression or distant metastasis

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Preoperative Folfirinox, Radiation Therapy for Resectable Adenocarcinoma of the Pancreas	NCT01560949	Pancreatic Canc...	Oxaliplatin Irinotecan 5-FU Gemcitabine Radiation Thera...	18 Years -	M.D. Anderson Cancer Center
Preoperative Folfirinox, Radiation Therapy for Resectable Adenocarcinoma of the Pancreas	NCT01560949	Pancreatic Canc...	Oxaliplatin Irinotecan 5-FU Gemcitabine Radiation Thera...	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for high risk resectable