MFOLFIRINOX And Stereotactic Radiotherapy (SBRT) for Pancreatic Cancer With High Risk and Locally Advanced Disease (MASTERPLAN)

Australasian Gastro-Intestinal Trials Group

Status and phase: Unknown; Phase 2

Conditions: Pancreatic Cancer

Treatments: Radiation: Stereotactic Radiotherapy (SBRT); Drug: mFOLFIRINOX; Drug: Gemcitabine + Capecitabine; Drug: Gemcitabine + Nab-paclitaxel; Procedure: Pancreatoduodenectomy (Whipple procedure)

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT04089150

CTC 0245/AGITG AG0118PS

Details and patient eligibility

About

This is a prospective, multicentre randomised, phase II clinical trial, with randomisation 2:1 by minimisation and stratification by tumour stage, planned chemotherapy and institution.

Full description

This is a prospective, multicentre randomised, phase II clinical trial to evaluate safety and activity of stereotactic body radiotherapy (SBRT) in addition to chemotherapy in patients with high-risk and borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC). High risk defined as any patient with tumour >4cm, extrapancreatic extension or node positive disease.

Enrollment: 120 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adults, aged between 18-75 years, with histological confirmation of pancreatic adenocarcinoma

• Any of the following

  1. T3 (tumour >4 cm)
  2. Extrapancreatic extension
  3. Node positive (stage IIB)
  4. Borderline resectable pancreatic cancer, locally advanced pancreatic cancer

• Measurable disease according to RECIST v1.1

• ECOG performance status 0-1

• Adequate renal and haematological function

• Adequate hepatic function. Defined as bilirubin <1.5 X ULN (Upper Limit of Normal), AST + ALT <3.0 X ULN. In patients who have had a recent biliary drainage and whose bilirubin is descending, a value of ≤ 3 X N is acceptable

• Study treatment planned to start within 14 days of registration

• Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments

• Signed, written informed consent

Exclusion criteria

• Tumour size greater than 70mm
• Prior abdominal radiotherapy
• Evidence of metastatic disease on baseline radiologic investigations
• History of another malignancy within 2 years prior to randomisation, except adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial transitional cell carcinoma of the bladder, or any Stage 1 endometrial carcinoma. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 2 years after definitive primary treatment
• Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
• Neuroendocrine pancreatic carcinoma
• Life expectancy of less than 3 months
• Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must use a reliable means of contraception
• Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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120 participants in 2 patient groups

Arm A

Active Comparator group

Description:

* Option 1: fluorouracil(5-FU)/leucovorin/irinotecan/oxaliplatin (mFOLFIRINOX) (6 cycles) * Option 2: gemcitabine + nab-paclitaxel (3 cycles) * Resectable patients receive surgery 6 weeks post completion of initial chemotherapy * Unresectable patients continue with ongoing chemotherapy (option 1 or option 2) * Unresectable patients with locoregional progression or metastatic disease, chemotherapy treatment at the discretion of treating medical oncologist * Adjuvant chemotherapy for resectable patients to begin within 8 weeks after surgery * For patients who received option 1 chemotherapy: 12 weeks of mFOLFIRINOX * For patients who received option 2 chemotherapy: 12 weeks of mFOLFIRINOX or 12 additional weeks of gemcitabine/capecitabine

Treatment:

Procedure: Pancreatoduodenectomy (Whipple procedure)

Drug: Gemcitabine + Capecitabine

Drug: Gemcitabine + Nab-paclitaxel

Drug: mFOLFIRINOX

Arm B

Experimental group

Description:

* Option 1: fluorouracil(5-FU)/leucovorin/irinotecan/oxaliplatin (mFOLFIRINOX) (6 cycles) * Option 2: gemcitabine + nab-paclitaxel (3 cycles) * Stereotactic Radiotherapy (SBRT) to commence within 3 weeks of completing initial chemotherapy: 40 Gray (Gy) in 5 fractions over 2 weeks * Resectable patients receive surgery 6 weeks post completion of initial chemotherapy * Unresectable patients continue with ongoing chemotherapy (option 1 or option 2) * Unresectable patients with locoregional progression or metastatic disease, chemotherapy treatment at the discretion of treating medical oncologist * Adjuvant chemotherapy for resectable patients to begin within 8 weeks after surgery * For patients who received option 1 chemotherapy: 12 weeks of mFOLFIRINOX * For patients who received option 2 chemotherapy: 12 weeks of mFOLFIRINOX or 12 additional weeks of gemcitabine/capecitabine

Treatment:

Procedure: Pancreatoduodenectomy (Whipple procedure)

Drug: Gemcitabine + Capecitabine

Drug: Gemcitabine + Nab-paclitaxel

Drug: mFOLFIRINOX

Radiation: Stereotactic Radiotherapy (SBRT)