Panitumumab as second line therapy for advanced pancreatic ductal adenocarcinoma with wild-type KRAS gene

• Register: ANZCTR
• Last refreshed on: 11 November 2019
• Main ID: ACTRN12617000540314
• Date of registration: 13/04/2017
• Prospective Registration: Yes
• Primary sponsor: Dr Daniel Croagh
• Public title: Panitumumab as second line therapy for advanced pancreatic ductal adenocarcinoma with wild-type KRAS gene
• Scientific title: Efficacy of Epidermal Growth Factor Receptor (EGFR) inhibitor Panitumumab for the treatment of KRAS wild-type unresectable or metastatic pancreatic ductal adenocarcinoma
• Date of first enrolment: 20/03/2018
• Target sample size: 24
• Recruitment status: Suspended
• URL: https://anzctr.org.au/ACTRN12617000540314.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Parallel;Type of endpoint: Efficacy;
• Phase: Phase 2

Countries of recruitment

Australia

Contacts

• Name: Dr Joanne Lundy

• Name: Dr Daniel Croagh

Key inclusion & exclusion criteria

Inclusion criteria: i. Adults, age 18 years or over, male or female
ii. Locally advanced (unresectable), recurrent or metastatic biopsy-proven PDAC (note: patients with ampullary and peri-ampullary tumours will also be allowed, providing they meet all other inclusion criteria)
iii. KRAS wild-type PDAC (for panitumumab treatment arm)
iv. ECOG performance status 0-2
v. Measurable disease as per the response evaluation criteria in RECIST guideline version 1.1
vi. Progressive disease following first line chemotherapy - defined as an increase in CA 19.9 of 30% above that recorded at the end of first line therapy (confirmed on 2 blood draws) or evidence of progressive disease on standard imaging using CT scans.
vii. Patients whose tumours recur within 12 months of the completion of adjuvant chemotherapy and are otherwise eligible for this study will be considered to have received “first line chemotherapy” for the purposes of this study. Patients who have received more than one line of chemotherapy may be considered on an individual basis, if they meet all other eligibility criteria.
viii. Adequate bone marrow function; (ANC more than or equal to 1500/mcL, platelets more than or equal to 100 000/mcL, haemoglobin more than or equal to 9g/dL)
ix. Adequate renal function; calculated creatinine clearance (CrCl) greater than or equal to 50ml/min (Cockcroft-Gault formula) or Creatinine less than or equal to 1.5 XULN
x. Adequate hepatic function; serum total bilirubin less than or equal to 1.5 times ULN, ALT/AST less than or equal to 2.5 times ULN (or less than or equal to 5 times ULN with documented liver metastases), ALP less than or equal to 5 times ULN, and INR less than or equal to 1.5
xi. Provision of informed consent for participation in the study
Exclusion criteria: i. Pancreatic neuroendocrine tumours, cholangiocarcinoma affecting the supra-pancreatic bile duct and tumours metastatic to the pancreas (e.g. renal cell carcinoma)
ii. Children, persons younger than 18 years of age
iii. Pregnancy or lactation
iv. Active or uncontrolled infection
v. Previous treatment with EGFR inhibitor
vi. Previous radiotherapy to the pancreas if this is the only site of measurable disease (unless there is demonstrated, clear evidence of radiological progression at the site since the completion of radiotherapy).
vii. Hypersensitivity to study drug
viii. Previous or current interstitial lung disease
ix. Previous or current pulmonary fibrosis
x. History of another malignancy within 2 years prior to allocation. (NB. Patients with adequately treated carcinoma in-situ, curatively treated uterine cervix carcinoma in-situ or non-melanoma skin carcinoma, or superficial transitional cell carcinoma of the bladder remain eligible even if diagnosed less than 2 years earlier. Patients with a history of other malignancy are eligible if they have been continuously disease-free for at least 2 years following definitive treatment.)
xi. Any severe or uncontrolled medical conditions within 3 months prior to allocation, including but not limited to:
Unstable cardiac disease, myocardial infarction or uncontrolled arrhythmia
Cirrhosis, active or chronic Hepatitis B infection, Hepatitis C infection, HIV seropositivity
Active bleeding diathesis
Renal failure
Unstable diabetes

Age minimum: 18 Years
Age maximum: No limit
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Cancer - Pancreatic

KRAS wild-type unresectable or metastatic pancreatic ductal adenocarcinoma;
KRAS wild-type unresectable or metastatic pancreatic ductal adenocarcinoma

Intervention(s)

Following determination of KRAS status, verification of eligibility for this study and informed consent participants will receive study treatment. KRAS wild type patients will be enrolled in the treatment arm, and will be administered panitumumab at a dose of 6mg/kg IV once every 2 weeks. The study drug, panitumumab, will be given as a sole agent for 4 months. Participants can receive chemotherapy in addition to the study treatment after the first 4 months, at the discretion of the treating clinician in consultation with the patient. Participants can continue on study treatment for up to 24 months.

Premedication should be given as per local site’s usual practices and supportive care provided at each treating clinician’s discretion and the local institution’s normal standard of care. Prophylactic antibiotic therapy to prevent or reduce the severity of the rash is highly recommended. Adherence to therapy will be monitored by medical review prior to each cycle.

Treatment assessments will include routine history and physical examination, evaluation for adverse events, routine laboratory testing, quality of life questionnaires (EORTC QLQ-C30 version 3.0), and CT scans of the chest, abdomen and pelvis. PET-CT and Ca19.9 will be performed at 4 and 8 weeks for all KRAS wild type patients who remain on panitumumab, and objective tumour response will be evaluated every 8 weeks according to RECIST criteria version 1.1.

Primary Outcome(s)

Progression-free survival (PFS), assessed by CT scan using RECIST 1.1 criteria
[Measured at 4 months]

Secondary Outcome(s)

Quality of life
[The EORTC QLQ-C30 version 3.0 questionnaire will be used to evaluate participant quality of life at 4 weeks, 16 weeks and at the end of treatment]

Feasibility of selecting patients for personalized therapy, defined as the proportion of the screened patients who start study treatment
[At conclusion of trial]

Metabolic Response Rate (MRR) to Panitumumab, assessed by PET scan and serum Ca19.9 levels.[At 4 weeks]

Safety (including toxicity and morbidity of treatment). Adverse events will be graded and recorded at each assessment, using the NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0.[Adverse events will be graded and recorded every 2 weeks while on study treatment, and after finishing treatment once more at a 30 day follow up assessment, ]

Overall survival, measured in days from the date of treatment initiation to date of death.[Following completion of therapy, patient status will be monitored every 8 weeks for survival assessment.
]

Objective tumour response rate (OTRR), defined as the sum of the partial and complete responders (as defined by RECIST criteria version 1.1) expressed as a proportion of the total number of patients.[Assessed as per RECIST criteria version 1.1 every 8 weeks for up to 2 years. ]

Progression free survival, as measured in days from the date of treatment initiation to the date of first evidence of disease progression or death, whichever occurs first.[Assessed by PET/CT at 8 weeks, then CT chest, abdomen and pelvis every 8 weeks according to RECIST criteria version 1.1. ]

Secondary ID(s)

Nil known

Source(s) of Monetary Support

Monash Comprehensive Cancer Consortium

Cook Medical

Epworth Research Institute

Amgen Australia

Monash Health

Ethics review

Status: Approved
Approval date:
Contact:

Monash Health HREC