Clinical trial NCT01591733: FOLFIRINOX + RT for Pancreatic Cancer
Official title: Phase II Study of Preoperative FOLFIRINOX Followed by Accelerated Short Course Radiation Therapy for Borderline-Resectable Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: Borderline resectable
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2012-05-04
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of a therapy to learn whether the therapy works in treating a specific cancer. "Investigational" means that the therapy is still being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if therapy is effective for treating different types of cancer. Proton beam radiation therapy is an FDA (U.S. Food and Drug Administration) approved radiation delivery system.

Proton beam radiation therapy is known to spare surrounding normal tissues from radiation as it delivers less radiation beyond the area of the target tissues. This may reduce side effects that patients would normally experience with standard (photon) radiation therapy, which tends to include more normal tissue along with tumor target tissue.

Researchers in the laboratory have discovered that there are pathways inside the cells that can lead to growth and survival of the tumor. The chemotherapy drugs FOLFIRINOX and capecitabine are targeted towards blocking the pathways that allow cancer cells to divide, and may result in the tumor shrinking in size.

In this research study, the investigators are looking to determine if proton beam radiation in combination with FOLFIRINOX and capecitabine is effective in controlling the growth of your cancer.

Detailed description: For weeks 1-8, you will only be receiving FOLFIRINOX via IV infusion. The treatment plan will begin with four cycles (8 weeks) of FOLFIRINOX. Each cycle is 14 days long. You will receive FOLFIRINOX therapy on days 1, 2 and 3 of each of the four cycles. The FOLFIRINOX treatment is broken up into three different drugs. 5-FU will be administered over two hours on day one of each cycle, and then continuously with a pump for days 2 and 3. Oxaliplatin will be delivered by intravenous (infusion) over 120 minutes. Irinotecan will be given by IV for 90 minutes. All parts of this treatment will be received as an outpatient.

If after 4 cycles of FOLFIRINOX therapy, your tumor has not spread, you will receive a further 4 cycles of FOLFIRINOX. If after 8 total cycles of FOLFIRINOX your cancer is clearly resectable, you will proceed to phase 2 of treatment with capecitabine and radiation therapy.

You will take tablets of capecitabine by mouth for a total of 10 days (Monday through Friday) during the two weeks after your FOLFIRINOX treatment.

You will be given a drug diary for capecitabine which contains instructions on how to take the drug.

Short course radiation: You will receive proton radiation treatment for five days (Monday through Friday) after your FOLFIRINOX treatment, during the time of your capecitabine treatment, or photon radiation for ten days (Monday through Friday for two weeks). You will also be assessed at least once during this treatment course for any side effects you may be experiencing.

You will receive study radiation treatment as an outpatient at the Francis H. Burr Proton Center or the Clark Center for Radiation Oncology at the Massachusetts General Hospital Surgery is expected to occur approximately one to four weeks after completion of capecitabine therapy.

After your surgery, you may receive additional chemotherapy at the discretion of your treating physician and be followed as per standard of care.

Eligibility criteria: Inclusion Criteria:

* Cytologic or histologic proof pancreatic ductal carcinoma
* Borderline resectable
* Life expectancy of at least 3 months
* ECOG Performance Status ≤ 1
* Adequate organ and bone marrow function
* No treatment of other invasive cancers within the last 5 years with 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
* \> 4 weeks since major surgery, excluding laparoscopy

Exclusion Criteria:

* Evidence of metastatic disease
* Pregnant or breastfeeding
* Other serious uncontrolled medical conditions
* Prior chemotherapy, targeted/biologic therapy or radiation for treatment of the pancreatic tumor
* Prior systemic fluoropyrimidine therapy
* History of uncontrolled seizures, central nervous system disorders or psychiatric disability
* Individuals on cimetidine

Primary outcomes:
measure: Rate of R0 Resection
timeFrame: Post-surgery (about 4 months post baseline)
Secondary outcomes:
measure: Median Progression-Free Survival
timeFrame: From the start of treatment until death or disease progression, median duration of follow-up of 14.7 months
measure: Median Overall Survival
timeFrame: From the start of treatment until the time of death, median duration of follow-up of 37.7 months
measure: Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation
timeFrame: From the start of treatment until the end of chemoradiation, about 4 months
measure: The Proportion of Participants With Surgery Related Adverse Events
timeFrame: At the time of surgery, 30 days post-surgery
measure: 30 Day Post-operative Mortality Rate
timeFrame: 30 days post surgery (about 6 months from baseline)
measure: Rate of Pathologic Downstaging
timeFrame: Baseline, Post surgery
measure: Local Control Rates
timeFrame: From the start of treatment until the end of treatment with FOLFIRINOX, or until disease progression (median duration of follow-up of approximately 14 months)
measure: Correlation of Mutational Analysis Biomarkers
timeFrame: 2 years
measure: Quality of Life, Symptom Burden, and Mood
timeFrame: 2 years
measure: Utilization of Health Services (Emergency Room, Hospital and Intensive Care Unit)
timeFrame: 2 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Theodore S Hong, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Murphy JE, Wo JY, Ryan DP, Jiang W, Yeap BY, Drapek LC, Blaszkowsky LS, Kwak EL, Allen JN, Clark JW, Faris JE, Zhu AX, Goyal L, Lillemoe KD, DeLaney TF, Fernandez-Del Castillo C, Ferrone CR, Hong TS. Total Neoadjuvant Therapy With FOLFIRINOX Followed by Individualized Chemoradiotherapy for Borderline Resectable Pancreatic Adenocarcinoma: A Phase 2 Clinical Trial. JAMA Oncol. 2018 Jul 1;4(7):963-969. doi: 10.1001/jamaoncol.2018.0329.