PRIMUS002: Looking at 2 Neo-adjuvant Treatment Regimens for Resectable and Borderline Resectable Pancreatic Cancer

NCT04176952 | Terminated Phase 2 DMC

• 1 other identifier: PRIMUS0022016
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 3

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

Conditions

Neoplasms Pancreatic

Outcome Measures

Primary Outcomes (1)

• Time to progression post FOLFOX-A induction treatment

  date of progression after FOLFOX-A neo-adjuvant chemotherapy as assessed by RECIST 1.1

  CT scans will take place at baseline, pre chemoradiotherapy and pre surgery, over approximately 6 months

Secondary Outcomes (13)

• Proving liquid biopsies can be used to define patient subgroups

  From date of registration to date of surgery. On average 4 months after registration

• Response post neo-adjuvant chemotherapy

  CT scan will be performed at baseline and then post neo-adjuvant chemotherapy (approximately 3 months later)

• College of American Pathologists tumour regression grade

  Post surgery which will be approximately 4 months post registration

• R0 rate post surgery

  Post surgery which will be approximately 4 months post registration

• Overall survival

  From date of registration until date of death assessed for up to 5 years post registration

Study Arms (2)

FOLFOX-A

EXPERIMENTAL

FOLFOX A arm (14-day cycle) * nab-paclitaxel: 150mg/m2 IV over 30 minutes, day 1 (administered first). * Oxaliplatin: 85mg/m2, IV over 2 hours, day 1. * Folinic acid: 350mg flat dose, IV over 2 hours, day 1. * Fluorouracil infusion:1200mg/m2/day, as a continuous IV infusion over 2 days, day 1 and day 2 (for a total dose of 2400mg/m2 over 46 hours or 48 hours as per local practice.) Patients will also receive daily G-CSF as primary prophylaxis against neutropenic events for all cycles. This should be given as per local policy for chemotherapy regimens given every 14 days e.g. it may be started on day 4 for 7 days (preparation and dose should be given as per local policy).

Drug: FOLFOX-A

Abraxane and Gemcitabine

ACTIVE COMPARATOR

Nab-Paclitaxel + Gemcitabine (AG) arm (28-day cycle) * nab-paclitaxel: 125mg/m2 IV over 30 minutes on days 1, 8 and 15 (administered first). * Gemcitabine 1000mg/m2 IV over 30 minutes on days 1, 8 and 15 (immediately following nab-paclitaxel).

Drug: AG

Interventions

FOLFOX-A DRUG

* nab-paclitaxel: 150mg/m2 IV over 30 minutes, day 1 (administered first). * Oxaliplatin: 85mg/m2, IV over 2 hours, day 1. * Folinic acid: 350mg flat dose, IV over 2 hours, day 1. * Fluorouracil infusion:1200mg/m2/day, as a continuous IV infusion over 2 days, day 1 and day 2 (for a total dose of 2400mg/m2 over 46 hours or 48 hours as per local practice.)

FOLFOX-A

AG DRUG

* nab-paclitaxel: 125mg/m2 IV over 30 minutes on days 1, 8 and 15 (administered first). * Gemcitabine 1000mg/m2 IV over 30 minutes on days 1, 8 and 15 (immediately following nab-paclitaxel).

Abraxane and Gemcitabine

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Signed informed consent given for PRIMUS 002 study
• Age ≥ 16 years
• Resectable or borderline resectable pancreatic cancer as defined by National Comprehensive Cancer Network criteria following discussion at the Multi Disciplinary Team
• Measurable Disease as per RECIST 1.1
• Histological or cytologically proven pancreatic ductal adenocarcinoma (including variants)
• Able to undergo biliary drainage using a covered or partially covered self-expanding metal stent if jaundiced
• Eastern Cooperative Oncology Group performance status 0 and 1
• Adequate liver/bone marrow function as defined by:
• Neutrophils (ANC) ≥ 1.5 x 109/l
• Platelets ≥ 100 x 109/l
• Haemoglobin ≥ 9.0g/dL
• White Blood Cells (WBC) ≥ 3 x 109/l
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) unless bilirubin rise is due to Gilbert's syndrome
• Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN (or \<5 x ULN in the presence of liver metastases)

You may not qualify if:

• Distant metastatic disease
• 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
• Prior chemotherapy or CRT for pancreatic cancer
• Known hypersensitivity for any component of any study drug
• Active infection including Herpes Zoster and chickenpox
• Uncontrolled congestive heart failure (CHF), or history of myocardial ischemia (MI), unstable angina, stroke, or transient ischemia within previous 6 months.
• Serious medical or psychological condition precluding neo-adjuvant treatment and surgical resection
• New York Heart Association Classification Grade III or IV
• Liver cirrhosis (except for Child-Pugh A)
• Major surgery within 28 days prior to trial entry
• 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
• Patients with known malabsorption
• Patients with known or suspected dihydropyrimidine dehydrogenase (DPD) deficiency
• Grade ≥ 2 peripheral neuropathy
• Administration of any investigational drug within 28 days or 5 half-lives, whichever is longer, prior to receiving the first dose of trial treatment

Sponsors & Collaborators

• Judith Dixon-Hughes: lead
• NHS Greater Glasgow and Clyde: collaborator
• University of Glasgow: collaborator

Study Sites (3)

Western General

Edinburgh, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom

Location

Royal Free Hospital

London, United Kingdom

Location

Related Publications (1)

• Saha A, Wadsley J, Sirohi B, Goody R, Anthony A, Perumal K, Ulahanan D, Collinson F. Can Concurrent Chemoradiotherapy Add Meaningful Benefit in Addition to Induction Chemotherapy in the Management of Borderline Resectable and Locally Advanced Pancreatic Cancer?: A Systematic Review. Pancreas. 2023 Jan 1;52(1):e7-e20. doi: 10.1097/MPA.0000000000002215.

  PMID: 37378896 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Derek Grose

  NHS Greater Glasgow and Clyde

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Project Manager

Model Details: Patients are registered to receive either FOLFOX-A or AG depending on their age and performance status

Study Record Dates

• First Submitted: October 28, 2019
• First Posted: November 26, 2019
• Study Start: March 5, 2019
• Primary Completion: August 19, 2021
• Study Completion: August 19, 2021
• Last Updated: May 24, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: Once clinical study report has been written and primary publication accepted by peer reviewed journal
• Access Criteria: On request to trial management group

Locations

GB (3)