FOLFIRINOX + RT for Pancreatic Cancer

Pancreatic Cancer Clinical Trial

Official title:

Phase II Study of Preoperative FOLFIRINOX Followed by Accelerated Short Course Radiation Therapy for Borderline-Resectable Pancreatic Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01591733
• Other study ID #: 11-328
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 2012
• Est. completion date: January 2022

Study information

• Verified date: May 2021
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 48
• Est. completion date: January 2022
• Est. primary completion date: March 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• FOLFIRINOX
Up to Eight-14 day cycles
• Capecitabine
Orally, for 10 days

Radiation:
• Short Course Radiation
Five or ten days

Procedure:
• Surgery
1-4 weeks after completion of capecitabine therapy

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of R0 Resection	The rate of R0 resection of patients with borderline-resectable adenocarcinoma of the head of the pancreas, along with borderline-resectable and resectable adenocarcinoma of the body and tail of the pancreas. R0 resection means that following surgery, no cancer cells are seen microscopically at the resection margin.	Post-surgery (about 4 months post baseline)
Secondary	Median Progression-Free Survival	The median progression free survival as measured from the start of treatment until the time of disease progression or death, whichever occurs first. Disease status was evaluated using RECIST (Response Evaluation Criteria in Solid Tumors). Disease progression is defined as having at least a 20% increase in the sum of the longest diameter (LD) of target lesion, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.	From the start of treatment until death or disease progression, median duration of follow-up of 14.7 months
Secondary	Median Overall Survival	Median overall survival, as measured from the start of treatment until the time of death.	From the start of treatment until the time of death, median duration of follow-up of 37.7 months
Secondary	Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation	Frequency of grade 3 or greater adverse events deemed related to FOLFIRINOX+short course radiation therapy. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE 4).	From the start of treatment until the end of chemoradiation, about 4 months
Secondary	The Proportion of Participants With Surgery Related Adverse Events	The number of participants with surgery related any grade adverse events following pancreaticoduodenectomy or distal pancreatectomy after receiving preoperative FOLFIRINOX and preoperative short course radiation therapy. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE 4).	At the time of surgery, 30 days post-surgery
Secondary	30 Day Post-operative Mortality Rate	The number of participants that died within 30 days after undergoing pancreaticoduodenectomy or distal pancreatectomy.	30 days post surgery (about 6 months from baseline)
Secondary	Rate of Pathologic Downstaging	To determine the rate of pathologic down-staging among participants that underwent pancreaticoduodenectomy or distal pancreatectomy. The pathologic downstaging rate is the proportion of patients with the primary tumor and nodes downstaged based on final pathology of the surgical specimen.	Baseline, Post surgery
Secondary	Local Control Rates	The number of participants that achieved local control. Local control was evaluated using RECIST (Response Evaluation Criteria in Solid Tumors). Local Failure is defined as progression of the primary tumor, or to the reappearance of tumor at the primary site.	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)
Secondary	Correlation of Mutational Analysis Biomarkers	To correlate mutational analysis biomarkers (SNaPSHOT assay) with response to treatment	2 years
Secondary	Quality of Life, Symptom Burden, and Mood	Patient-reported outcomes: We will use descriptive statistics to describe Quality of Life (QOL) (EORTC QLQ-C30), symptom burden (ESAS-r) and mood (HADS) for the entire study cohort.	2 years
Secondary	Utilization of Health Services (Emergency Room, Hospital and Intensive Care Unit)	Summary of the number of hospitalizations, intensive care unit (ICU) stays, emergency department (ED) stays, and palliative care use for the study population.	2 years