Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000540314
Ethics application status
Approved
Date submitted
7/04/2017
Date registered
13/04/2017
Date last updated
5/11/2019
Date data sharing statement initially provided
6/11/2018
Type of registration
Prospectively registered

Titles & IDs
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
Secondary ID [1] 291647 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
KRAS wild-type unresectable or metastatic pancreatic ductal adenocarcinoma 302796 0
Condition category
Condition code
Cancer 302294 302294 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 297727 0
Treatment: Drugs
Comparator / control treatment
In the observation arm of the study, two KRAS mutant patients undergoing alternative/standard second line chemotherapy will be enrolled for every one patient enrolled into the treatment arm. Following the enrolment of a patient in the treatment arm, the next two KRAS mutant patients who are both eligible and give consent will be selected for entry into the observation arm. The assessments will be identical to the treatment cohort, with the exception of the 4 and 8 week PET scans.
Control group
Active

Outcomes
Primary outcome [1] 301702 0
Progression-free survival (PFS), assessed by CT scan using RECIST 1.1 criteria
Timepoint [1] 301702 0
Measured at 4 months
Secondary outcome [1] 333598 0
Metabolic Response Rate (MRR) to Panitumumab, assessed by PET scan and serum Ca19.9 levels.
Timepoint [1] 333598 0
At 4 weeks
Secondary outcome [2] 333599 0
Feasibility of selecting patients for personalized therapy, defined as the proportion of the screened patients who start study treatment
Timepoint [2] 333599 0
At conclusion of trial
Secondary outcome [3] 333601 0
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.
Timepoint [3] 333601 0
Assessed by PET/CT at 8 weeks, then CT chest, abdomen and pelvis every 8 weeks according to RECIST criteria version 1.1.
Secondary outcome [4] 333602 0
Overall survival, measured in days from the date of treatment initiation to date of death.
Timepoint [4] 333602 0
Following completion of therapy, patient status will be monitored every 8 weeks for survival assessment.
Secondary outcome [5] 333604 0
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.
Timepoint [5] 333604 0
Assessed as per RECIST criteria version 1.1 every 8 weeks for up to 2 years.
Secondary outcome [6] 333606 0
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.
Timepoint [6] 333606 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,
Secondary outcome [7] 333608 0
Quality of life
Timepoint [7] 333608 0
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

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
In the observation arm of the study, two KRAS mutant patients undergoing alternative/standard second line chemotherapy will be enrolled for every one patient enrolled into the treatment arm. Following the enrolment of a patient in the treatment arm, the next two KRAS mutant patients who are both eligible and give consent will be selected for entry into the observation arm.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
In this study, 100-200 patients will be screened. With an expected prevalence of KRAS mutation of 80%, we will recruit up to 19 patients for the therapeutic component of the study. There will be stopping rules for futility after 8 patients.

A 50% progression free survival rate (PFS) at 4 months would be considered to be worthwhile to demonstrate activity of panitumumab. The study will initially enrol 8 patients when an assessment will be made in order to rule out futility. Futility will be declared if all 8 patients have progressed within 4 months and no MRR is observed upon which consideration will be given to either modifying the design or stopping the study for futility.  In the absence of more than one MRR being observed in the first eight patients, a decision to continue the study and recruit a further 11 patients (making 19 in total) may be made guided by the strength of the PFS at 4 months rate. The MRR and PFS at 4 months rates in the full cohort could then be determined together with the degree of uncertainty surrounding these rates.

The further 11 patients will be recruited in a stepwise fashion.  After 13 patients have been enrolled and assessed, if still only 1 MRR is observed then the study could re-assessed as to whether to continue to the 19 or stop for futility depending on the PFS rate. If all 13 patients have also progressed by 4 months then the study may stopped at this point. However if at least one patient has as a PFS > 4 months then continuing to the 19 patients may still be an option.

Recruitment
Recruitment status
Suspended
Date of first participant enrolment
Anticipated
1/11/2017
Actual
20/03/2018
Date of last participant enrolment
Anticipated
1/11/2019
Actual
21/05/2019
Date of last data collection
Anticipated
21/11/2019
Actual
Sample size
Target
24
Accrual to date
4
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 7800 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment postcode(s) [1] 15734 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 296139 0
Commercial sector/Industry
Name [1] 296139 0
Amgen Australia
Country [1] 296139 0
Australia
Funding source category [2] 296141 0
Other Collaborative groups
Name [2] 296141 0
Monash Comprehensive Cancer Consortium
Country [2] 296141 0
Australia
Funding source category [3] 296142 0
Other
Name [3] 296142 0
Epworth Research Institute
Country [3] 296142 0
Australia
Funding source category [4] 296143 0
Commercial sector/Industry
Name [4] 296143 0
Cook Medical
Country [4] 296143 0
Australia
Funding source category [5] 296144 0
Hospital
Name [5] 296144 0
Monash Health
Country [5] 296144 0
Australia
Primary sponsor type
Individual
Name
Dr Daniel Croagh
Address
Department of Surgery
Upper GI and HPB
Monash Medical Centre
246 Clayton Rd, Clayton VIC 3168
Country
Australia
Secondary sponsor category [1] 295036 0
None
Name [1] 295036 0
Address [1] 295036 0
Country [1] 295036 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297391 0
Monash Health HREC
Ethics committee address [1] 297391 0
Ethics committee country [1] 297391 0
Australia
Date submitted for ethics approval [1] 297391 0
30/03/2017
Approval date [1] 297391 0
12/04/2017
Ethics approval number [1] 297391 0
16-0000-584A

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 73902 0
Dr Daniel Croagh
Address 73902 0
Department of Surgery
Upper GI and HPB
Monash Medical Centre
246 Clayton Rd, Clayton VIC 3168
Country 73902 0
Australia
Phone 73902 0
+61 3 9543 5311
Fax 73902 0
+61 3 9543 3805
Email 73902 0
[email protected]
Contact person for public queries
Name 73903 0
Joanne Lundy
Address 73903 0
Monash Medical Centre
246 Clayton Rd, Clayton VIC 3168
Country 73903 0
Australia
Phone 73903 0
+61 3 9594 6207
Fax 73903 0
Email 73903 0
[email protected]
Contact person for scientific queries
Name 73904 0
Daniel Croagh
Address 73904 0
Department of Surgery
Upper GI and HPB
Monash Medical Centre
246 Clayton Rd, Clayton VIC 3168
Country 73904 0
Australia
Phone 73904 0
+61 3 9543 5311
Fax 73904 0
+61 3 9543 3805
Email 73904 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data collected during the trial, after de-identification
When will data be available (start and end dates)?
Immediately following publication, no end date determined
Available to whom?
To researchers who provide a methodologically sound proposal, at the discretion of the Principal Investigator
Available for what types of analyses?
To achieve the aims in the approved proposal
How or where can data be obtained?
Access subject to approvals by Principal Investigator


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEUS-FNA Biopsies to Guide Precision Medicine in Pancreatic Cancer: Results of a Pilot Study to Identify KRAS Wild-Type Tumours for Targeted Therapy.2021https://dx.doi.org/10.3389/fonc.2021.770022
N.B. These documents automatically identified may not have been verified by the study sponsor.