Clinical trial NCT04176952: PRIMUS002: Looking at 2 Neo-adjuvant Treatment Regimens for Resectable and Borderline Resectable Pancreatic Cancer
Official title: PRIMUS002: An Umbrella Phase II Study Examining Two Neo-adjuvant Regimens (FOLFOX-A and AG) in Resectable and Borderline Resectable Pancreatic Ductal AdenoCarcinoma (PDAC), Focusing on Biomarker and Liquid Biopsy Development
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Neoplasms Pancreatic
Lead sponsor: University of Glasgow
Sponsor class: OTHER
Collaborators: name: NHS Greater Glasgow and Clyde
name: University of Glasgow
First posted: 2019-11-26
Enrollment: 31
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients are registered to receive either FOLFOX-A or AG depending on their age and performance status
Primary purpose: TREATMENT

Brief summary: PRIMUS 002 is looking at 2 different chemotherapy regimens in the neo-adjuvant setting for pancreatic cancer. Each treatment will be given for 3 months prior to surgery

Detailed description: This is an integrated, open label, non-randomised, phase II trial of 2 neo-adjuvant regimens (FOLFOX-A and AG) assessing efficacy and toxicity with integrated translational work. The study is powered on testing a proposed DNA damage response deficient biomarker for responsiveness in patients treated with FOLFOX-A; patients being treated with AG are recruited concurrently. The study has a prospective safety assessment of neo-adjuvant chemotherapy and neo-adjuvant chemotherapy followed by chemoradiotherapy consisting of conventional radiotherapy with concomitant capecitabine. This safety assessment will include all patients (FOLFOX-A and AG)

Eligibility criteria: Inclusion Criteria:

1. Patient has been enrolled in the Precision-Panc Master Protocol and their tissue has been deemed suitable for Next Generation Sequencing analysis (a Precision-Panc Master Protocol identifier will be required at the time of study enrolment)
2. Signed informed consent given for PRIMUS 002 study
3. Age ≥ 16 years
4. Resectable or borderline resectable pancreatic cancer as defined by National Comprehensive Cancer Network criteria following discussion at the Multi Disciplinary Team
5. Measurable Disease as per RECIST 1.1
6. Histological or cytologically proven pancreatic ductal adenocarcinoma (including variants)
7. Able to undergo biliary drainage using a covered or partially covered self-expanding metal stent if jaundiced
8. Eastern Cooperative Oncology Group performance status 0 and 1
9. Adequate liver/bone marrow function as defined by:

   1. Neutrophils (ANC) ≥ 1.5 x 109/l
   2. Platelets ≥ 100 x 109/l
   3. Haemoglobin ≥ 9.0g/dL
   4. White Blood Cells (WBC) ≥ 3 x 109/l
   5. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) unless bilirubin rise is due to Gilbert's syndrome
   6. Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN (or \<5 x ULN in the presence of liver metastases)
   7. Estimated creatinine clearance ≥ 60 mL/min (as calculated by Cockcroft and Gault or Wright formula or measured by EDTA clearance)
10. Negative serum Human Chorionic Gonadotropin (HCG) test for females with child bearing potential. Postmenopausal women must have been amenorrhoeic for at least 12 months to be considered of non-childbearing potential
11. Woman of child bearing potential, and men with female partners of child bearing potential, must agree to use adequate contraceptive measures (see section 7.1.11.1) for the duration of the study and for up to 6 months after the completion of study treatment.
12. Able to comply with protocol requirements and deemed fit for surgical resection, chemotherapy and CRT

Exclusion Criteria:

1. Distant metastatic disease
2. History of previous or concurrent malignancy diagnosis (except curatively treated basal cell carcinoma of skin or carcinoma in situ of cervix) in the last 3 years
3. Prior chemotherapy or CRT for pancreatic cancer
4. Known hypersensitivity for any component of any study drug
5. Active infection including Herpes Zoster and chickenpox
6. Uncontrolled congestive heart failure (CHF), or history of myocardial ischemia (MI), unstable angina, stroke, or transient ischemia within previous 6 months.
7. Serious medical or psychological condition precluding neo-adjuvant treatment and surgical resection
8. New York Heart Association Classification Grade III or IV
9. Liver cirrhosis (except for Child-Pugh A)
10. Major surgery within 28 days prior to trial entry
11. Any patients receiving treatment with brivudin, sorivudin and analogues or patients who have not stopped these drugs at least 4 weeks prior to the start of study treatment
12. Any patient with severe diarrhoea (defined as ≥grade 3 diarrhoea despite maximum supportive measures and exclusion of underlying infection)
13. Patients with known malabsorption
14. Patients with known or suspected dihydropyrimidine dehydrogenase (DPD) deficiency
15. Grade ≥ 2 peripheral neuropathy
16. Administration of any investigational drug within 28 days or 5 half-lives, whichever is longer, prior to receiving the first dose of trial treatment

Primary outcomes:
measure: Time to progression post FOLFOX-A induction treatment
timeFrame: CT scans will take place at baseline, pre chemoradiotherapy and pre surgery, over approximately 6 months
Secondary outcomes:
measure: Proving liquid biopsies can be used to define patient subgroups
timeFrame: From date of registration to date of surgery. On average 4 months after registration
measure: Response post neo-adjuvant chemotherapy
timeFrame: CT scan will be performed at baseline and then post neo-adjuvant chemotherapy (approximately 3 months later)
measure: College of American Pathologists tumour regression grade
timeFrame: Post surgery which will be approximately 4 months post registration
measure: R0 rate post surgery
timeFrame: Post surgery which will be approximately 4 months post registration
measure: Overall survival
timeFrame: From date of registration until date of death assessed for up to 5 years post registration
measure: Disease free survival
timeFrame: from date of registration until date of disease recurrence assessed for at least 24 months post registration
measure: Safety and tolerability of study drugs: NCI CTCAE 4.03
timeFrame: Assessed at every clinic visit during treatment, for approximately 3 months post registration
measure: Safety and tolerability of chemoradiotherapy: NCI CTCAE 4.03
timeFrame: Assessed at every chemoradiotherapy visit and pre-surgery (once Chemoradiotherapy added). Chemoradiotherapy will take place 5 days a week for three weeks
measure: Surgical complication rate
timeFrame: Assessed post surgery, approximately 4 months post registration
measure: Neurotoxicity
timeFrame: Neurotoxicity will be assessed from registration until study is completed at various timepoints until patient death. Each patient will be followed up for at least 24 months post registration
measure: Quality of life assessed by EORTC QLQ-C30
timeFrame: Quality of life will be assessed from registration until study is completed at various timepoints until patient death. Each patient will be followed up for at least 24 months post registration
measure: Quality of life assessed by EORTC QLQ-PAN26
timeFrame: Quality of life will be assessed from registration until study is completed at various timepoints until patient death. Each patient will be followed up for at least 24 months post registration
measure: Health Economics
timeFrame: Health economics will be assessed from registration until study is completed at various timepoints until patient death. Each patient will be followed up for at least 24 months post registration
Other outcomes:
Locations:
city: Edinburgh
country: United Kingdom
facility: Western General
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: Royal Free Hospital
Study officials:
affiliation: NHS Greater Glasgow and Clyde
name: Derek Grose
role: PRINCIPAL_INVESTIGATOR
References: