Borderline Pancreas Study: FOLFIRINOX +SBRT

Resectable Pancreatic Cancer Clinical Trial

— GCC 1324  

Official title:

Neoadjuvant FOLFIRINOX and Stereotactic Body Radiotherapy (SBRT) Followed by Definitive Surgery for Patients With Borderline Resectable Pancreatic Adenocarcinoma: A Single-Arm Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01992705
• Other study ID #: HP-00055716
• Status: Completed
• Phase: Early Phase 1
• Start date: March 2014
• Est. completion date: September 27, 2018

Study information

• Verified date: August 2019
• Source: University of Maryland, Baltimore
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objective: To determine the rate of downstaging to resectability in patients with borderline resectable pancreatic cancer receiving FOLFIRINOX and SBRT as preoperative therapy.

Secondary Objective(s):

1. To assess the disease-free-survival, overall survival, time to recurrence and site of recurrence in patients with borderline resectable pancreatic cancer receiving preoperative FOLFIRINOX followed by SBRT

2. To investigate the safety and tolerability of FOLFIRINOX and SBRT in patients with resectable pancreatic cancer

3. To determine the radiologic and pathological response associated with preoperative SBRT and FOLFIRINOX therapy

4. To assess quality of life through and after treatment using the FACT-Hep questionnaire

Description:

The study investigators hypothesize that neoadjuvant FOLFIRINOX can be safely and efficaciously delivered using a sequential regimen with SBRT as an alternative to standard neoadjuvant chemoradiotherapy. Standard of care neoadjuvant treatment typically requires about six weeks of treatment with sub-systemic dosing of chemotherapy. The feasibility of the sequential delivery of the FOLFIRINOX followed by SBRT will be evaluated by capturing the prevalence of grade 3 toxicity and the treatment delay rate.

In our study, SBRT is planned sequentially to follow cycle 4 of chemotherapy treatment, provided toxicity has resolved to grade 2 or less. Thus, allowing for resolution of chemotherapy toxicity prior to initiation of radiation therapy. This interval and the fact that there is no concurrent delivery of chemo-RT, based on previously discussed experiences, including approaches where SBRT safely follows other intense chemotherapy regimens (see Polistina et al and Chuong [35,36]) makes this study feasible without establishing toxicity profile.

The proposed regimen of 4 cycles of FOLFIRINOX followed by 30 Gy/5 fractions using SBRT will be safely tolerated and will improve resectability rates in borderline resectable PDAC patients. In addition, this regimen will not compromise the ability to achieve a successful Whipple resection.

This regimen will improve the local control rate and overall disease free survival in this patient population. The investigators further hypothesize that early administration of FOLFIRNOX will provide optimal systemic therapy to control clinically occult micrometastases.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: September 27, 2018
• Est. primary completion date: September 27, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• = 18 years at diagnosis.

• Biopsy proven pancreatic adenocarcinoma.

• Borderline resectable per NCCN criteria (No distant metastases, venous involvement of the portal vein/SMV, demonstrating tumor abutment and narrowing of the lumen, encasement of the portal vein/SMV without encasement of the nearby arteries, or short-segment venous occlusion resulting from either tumor thrombus or encasement but with suitable vessel proximal or distal to this area of vessel involvement, allowing for safe resection and reconstruction; gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to the celiac axis; tumor abutment of the SMA not to exceed 180 degrees of the circumference of the vessel wall.).

• Radiologically measurable or clinically evaluable disease.

• Pancreas protocol CT and/or MRI if required for further clarification of disease tissue planes within 4 weeks of registration.

• ECOG PS of 0-2.

• Able to get a Whipple resection per surgeon assessment performed within 4 weeks of registration.

• The following laboratory values obtained = 28 days prior to registration:

• Absolute neutrophil count (ANC) = 1,500/mm3.

• Platelet count = 100,000/mm3.

• Hemoglobin > 8.0 g/dL.

• Total bilirubin = 1.5 x upper limit of normal (ULN).

• SGOT (AST) = 2 x ULN.

• SGPT (ALT) = 2 x ULN.

• Creatinine = 1.5 x ULN.

• CA 19-9 level (to establish baseline).

• A negative pregnancy test within 7 days prior to registration for women of childbearing potential. In addition, male and female participants must commit to adequate contraception while on study.

• Able to provide written informed consent.

• Willing to return for all required study assessments.

• Neurological assessment for pre-existing peripheral neuropathy.

• Documentation of pre-existing hearing deficits.

Exclusion Criteria:

• Any pancreatic adenocarcinoma that does not meet criteria for borderline resectable disease.

• Prior history of abdominal radiation therapy.

• History of autoimmune disease such as scleroderma, lupus, and inflammatory bowel disease.

• Patients with tumor-caused symptomatic bowel obstruction.

• Chemotherapy (including hormonal therapy) within the past 5 years from date of registration.

• Other invasive malignancies within the past 5 years from date of registration.

• Pregnant or nursing women or women of childbearing age that are unwilling to employ adequate contraception.

• Other co-morbid conditions which, based on the judgment of the physicians obtaining informed consent, would make the patient inappropriate for this study.

Related Conditions & MeSH terms

• Pancreatic Neoplasms
• Resectable Pancreatic Cancer

Intervention

Other:
• Chemotherapy(FOLFIRINOX) + SBRT prior to surgery if applicable
Patients will receive chemotherapy (21d/cycle for a total of 4 cycles) plus SBRT before screening for surgical resection of the pancreas.

Drug:
• -Oxaliplatin 85 mg/m2 IV on Day 1
Oxaliplatin 85 mg/m2 IV on Day 1 of each cycle (21d/cycle for a total of 4 cycles).
• -Irinotecan 180 mg/m2 IV on Day 1
Irinotecan 180 mg/m2 IV on Day 1 of each cycle (21d/cycle for a total of 4 cycles).
• -5-FU (Fluorouracil) 2,400 mg/m2 IV over 46-48 hours
5-FU (Fluorouracil) 2,400 mg/m2 IV over 46-48 hours of each cycle (21d/cycle for a total of 4 cycles.

Locations

Country	Name	City	State
United States	University of Maryland Medical Center	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
University of Maryland, Baltimore

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of adverse events/toxicites reported during and following treatment of FOLFIRINOX and SBRT in patients with resectable pancreatic cancer	Number of toxicities participants reported by participants during and following treatment with FOLFIRINOX and SBRT in patients with resectable pancreatic cancer (NIH CTCAE v.4).	Participants will be followed from randomization up to 120 months or death (from any cause) whichever comes first.
Other	Radiologic and pathological response associated with preoperative SBRT and FOLFIRINOX therapy	To determine the radiologic and pathological response associated with preoperative SBRT and FOLFIRINOX therapy (review of radiology and pathology reports).	Participants will be followed from randomization up to 120 months or death (from any cause) whichever comes first.
Other	Quality of life through and after treatment	To assess quality of life through and after treatment using the FACT-Hep questionnaire	Participants will be followed from randomization up to 120 months or death (from any cause) whichever comes first.
Primary	Rate of downstaging to resectability in patients with borderline resectable pancreatic cancer receiving FOLFIRINOX and SBRT as preoperative therapy.	To determine the rate of downstaging to resectability in patients with borderline resectable pancreatic cancer receiving FOLFIRINOX and SBRT as preoperative therapy (AGGC 6th edition).	Participants will be followed from randomization up to 120 months or death (from any cause) whichever comes first.
Secondary	Survival status (disease-free-survival vs. overall survival) time to recurrence and site of recurrence in patients with borderline resectable pancreatic cancer receiving preoperative FOLFIRINOX followed by SBRT	To assess the disease-free-survival, overall survival, time to recurrence and site of recurrence in patients with borderline resectable pancreatic cancer receiving preoperative FOLFIRINOX followed by SBRT (RECIST)	Participants will be followed from randomization up to 120 months or death (from any cause) whichever comes first.