Phase 2 Evaluation of Multi-modality Algorithm for Non-metastatic Adenocarcinoma of Pancreas or Ampulla

Phase 2

Terminated

Conditions: Ductal Adenocarcinoma of Pancreas
Adenocarcinoma of Ampulla

Interventions: Drug: Gemcitabine and nanoparticle albumin bound paclitaxel
Drug: 5-fluorouracil and irinotecan
Procedure: Definitive resection
Radiation: Preoperative chemoradiation

Registration Number: NCT02626520

Lead Sponsor: Essentia Health

Brief Summary: Patients diagnosed with pancreatic cancer without clinically detectable metastatic disease will be treated with standardized systemic chemotherapy, followed by chemoradiation, and then surgical resection for those with resectable or borderline resectable disease. The primary endpoint is disease-free survival at 1 yr from initiation of treatment.

Detailed Description: Patients with ductal adenocarcinoma of the pancreas (or ampulla) that have received no prior therapy and have no clinically detectable metastatic disease will be enrolled. Management will be driven by resectability status as defined by the American College of Surgeons. All patients will be defined at entry as Resectable, Borderline Resectable or Locally Advanced (Unresectable).

All patients will be treated initially with gemcitabine and nanoparticle albumin bound paclitaxel (nab-paclitaxel) every 14 days for 4 cycles. Patients classified as Resectable, who have CA19-9 below 180 and CA-125 below 30 will then proceed to resection. All other patients will get 5-fluorouracil as 46 hr infusion given with leucovorin and irinotecan (FOLFIRI-3) every 14 days x 4 cycles.

All patients without progression will then receive chemoradiation consisting of external beam radiotherapy (40 Gy in 20 fractions given over 4 weeks). During radiation all patients will receive radiosensitizing radiotherapy as: 5-fluorouracil at 225 mg/m2 5 days per week, Mitomycin-C at 3 mg.m2 on d1, 8, 15 \& 22; Cisplatin at 10 mg/m2 on d2, 9, 16, 23 and unfractionated heparin at 6,000 units/m2 daily in divided doses from day 1 to day 28.

After approximately 4 weeks to recover from chemoradiation, all patients with Resectable or Borderline Resectable disease will undergo definitive surgery.

Adjuvant therapy with FOLFIR-3 for an additional 6 cycles will be offered to all patients post-operatively.

Patients will then be actively followed every 3 to 6 months in keeping with National Comprehensive Cancer Network (NCCN) guidelines for 2 yrs, and then followed for recurrence, late toxicity and vital status every 6 months through 5 years.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 11

Inclusion Criteria

Histologic proof of adenocarcinoma consistent with ductal carcinoma of pancreas or ampulla, with no evidence of metastatic disease by clinical exam or cross-sectional imaging.
Fitness for chemotherapy in judgement of treating physician
Bilirubin < 4 (any means of biliary drainage acceptable)

Exclusion Criteria

Medical or mental illness precluding provision of informed consent
Pregnancy
Active infection for which neutropenia would pose high risk of mortality

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Locally Advanced	5-fluorouracil and irinotecan	Systemic chemotherapy followed by chemoradiation, followed by definitive surgery
Locally Advanced	Gemcitabine and nanoparticle albumin bound paclitaxel	Systemic chemotherapy followed by chemoradiation, followed by definitive surgery
Resectable, Low Risk	Gemcitabine and nanoparticle albumin bound paclitaxel	Systemic chemotherapy followed by definitive surgery without pre-operative or post-operative radiotherapy.
Resectable, Low Risk	Definitive resection	Systemic chemotherapy followed by definitive surgery without pre-operative or post-operative radiotherapy.
Locally Advanced	Preoperative chemoradiation	Systemic chemotherapy followed by chemoradiation, followed by definitive surgery
Locally Advanced	Definitive resection	Systemic chemotherapy followed by chemoradiation, followed by definitive surgery

Primary Outcome Measures

Name	Time	Method
Relapse Free Survival	1 yr form onset of treatment	Percentage of patients alive and free of detectable disease 1 yr from start of treatment

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Up to 3 years from registration	Time to death from any cause measured from start of treatment
R-0 Rate	Time of surgery	Rate of patients having surgery who have negative surgical margins (i.e. R-0 resection)