None listed
Conditions
Brief summary
The aim of this study is to test if panitumumab is a potentially useful treatment for pancreatic cancers which do not have mutations in the KRAS gene. Panitumumab has been shown to be effective in colon cancer, but only in those patients with cancers that lack a mutation in the KRAS gene. The fact that 90% of patients with pancreatic cancer have a mutation in the KRAS gene may explain why panitumumab has not been found to be effective when it has been administered to all patients with pancreatic cancer. Who is it for? You may be eligible to enroll in this trial if you are aged 18 or over and have been diagnosed with locally advanced (unresectable) or metastatic pancreatic ductal adenocarcinoma (PDAC) which has progressed following first line chemotherapy. Study details Participants enrolled who have KRAS wild-type PDAC will be allocated to the treatment arm. These participants will receive panitumumab by injection, once every two weeks for up to 24 months, with chemotherapy started at 4 months if your treating doctor determines that this would be beneficial. Participants enrolled who have KRAS mutated PDAC will be allocated to the observation group. These participants will receive standard treatment as determined by their treating doctor, and will simply complete trial assessments. Assessments for all participants will include CT scans and blood tests to monitor cancer progression for up to two years. It is hoped that the findings from this trial will provide information on whether panitumumab is an effective therapy for KRAS wild-type PDAC.
Interventions
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 clin
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.
Sponsors
Dr Daniel Croagh
Study design
Allocation
Non-randomised trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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
Outcome results
None listed