Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612000777897
Ethics application status
Approved
Date submitted
6/07/2012
Date registered
23/07/2012
Date last updated
20/01/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
The IMPACT trial: Individualised Molecular Pancreatic Cancer Therapy; a phase II trial assessing feasibility of personalised treatment based on specified tumour molecular signatures (phenotypes) of the tumour in patients with recurrent or metastatic pancreatic cancer.
Scientific title
A phase II trial assessing feasibility of personalised treatment based on specified tumour molecular signatures (phenotypes) of the tumour in patients with recurrent or metastatic pancreatic cancer.
Secondary ID [1] 280894 0
NIL
Universal Trial Number (UTN)
NIL
Trial acronym
IMPACT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced (metastatic or recurrent) pancreatic cancer 286802 0
Condition category
Condition code
Cancer 287110 287110 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Personalised Treatment (based on molecular phenotype):
1. HER2 positive sub-group - gemcitabine 1000mg/m2 over 30 minutes, given intravenously on days 1, 8 & 15 every 28 days until progression or unacceptable toxicity
plus
trastuzumab 4mg/kg intravenously day 1 only, followed by trastuzumab 2mg/kg given intravenously day 8, then weekly every subsequent week until progression or unacceptable toxicity or a total of 6 months treatment is completed.

2. Homologous recombinant defects subgroup - gemcitabine 1000mg/m2 over 30 minutes, given intravenously on days 1, 8 & 15 every 28 days until progression or unacceptable toxicity
plus
cisplatin 50 mg/m2 given intravenously over 60 minutes on days 1& 15 every 28 days until progression or unacceptable toxicity

3. antiEGFR responsive sub-group - gemcitabine 1000mg/m2 given intravenously days 1,8 & 15 each 28 day cycle until progression or unacceptable toxicity
plus
erlotinib 100mg orally daily continuously until progression or unacceptable toxicity
Intervention code [1] 285177 0
Treatment: Drugs
Comparator / control treatment
There is no comparator arm. This is a single arm study.
Control group
Active

Outcomes
Primary outcome [1] 287431 0
In the feasibility study, the primary objective is to determine the technical feasibility based on number of patients consented to molecular profiling, number of patients eligible and screened for the trial, number of patients eligible, recruitment, ability to deliver personalised treatment per protocol, safety and the ability to address any potential practical issues that may arise through the conduct of this trial.
Timepoint [1] 287431 0
After 10 patients have been recruited to the study.
Secondary outcome [1] 298131 0
Objective tumour response rate (OTRR) - partial (PR) or complete response (CR)
Timepoint [1] 298131 0
Tumour evaluation will follow the RECIST Version 1.1 guidelines and be used to determine response status (i.e. complete response, partial response, stable disease or progressive disease) at each assessment time point. The OTRR will be calculated by summing the number of patients assessed as having a complete or partial response and dividing this by the total number of patients evaluable for response (according to RECIST Version 1.1). Confirmation of a complete or partial response will be undertaken based on the results of the next scan performed (i.e. no additional scans to those presented in the Schedule of Assessments are required).
Secondary outcome [2] 298132 0
Overall survival (OS) (death from any cause)
Timepoint [2] 298132 0
Overall survival time is defined as the time from the date of registration to the date of death due to any cause. Overall survival time will be censored at the date of the last follow-up visit for patients who are still alive.
Secondary outcome [3] 298133 0
Safety (rates of adverse events)
Timepoint [3] 298133 0
The NCI Common Terminology Criteria for Adverse Events Version 4.0 (NCI CTCAE) will be used to classify and grade the intensity of adverse events after each treatment cycle.
Secondary outcome [4] 298134 0
Quality of life (QoL)(scores from patient-completed questionnaires)
Timepoint [4] 298134 0
Health-related Quality of Life assessment will be performed at baseline, then 4 weekly until disease progression.
The core EORTC QoL Questionnaire, QLQ-C30, will be used.
Secondary outcome [5] 298143 0
Clinical benefit at 4 months - complete response (CR) or partial response (PR) or stable disease (SD)
Timepoint [5] 298143 0
Tumour evaluation will follow the RECIST Version 1.1 guidelines and be used to determine response status (i.e. complete response, partial response, stable disease or progressive disease) at each assessment time point. The clinical benefit rate will be calculated by summing the number of patients assessed at 4 months as having a complete response, partial response, or stable disease and dividing this by the total number of patients evaluable for response at 4 months (according to RECIST Version 1.1). Confirmation of a complete or partial response will be undertaken based on the results of the next scan performed (i.e. no additional scans to those presented in the Schedule of Assessments are required).

Eligibility
Key inclusion criteria
1. Adult males or females 18 years or over with histologically confirmed primary adenocarcinoma of the pancreas who have cytological confirmation of recurrent or metastatic disease
2. Are currently enrolled in APGI and have consented through APGI to notify them if something of significance in regards to their cancer is found.
3. One of the following specified three molecular signatures:
*HER2 positive (HER2/neu over expression) subgroup; assessed using detailed DNA sequencing and RNA expression analysis and confirmed by HER2 ISH testing (using standard gastric cancer protocols).
*Homologous recombinant defects (BRCA1/BRCA2 or PALB2 mutation*) subgroup; assessed using detailed DNA sequencing and confirmed by PCR.
*antiEGFR responsive (KRAS WT or KRAS codon 13 mutation) subgroup; assessed using detailed DNA sequencing and confirmed by PCR (using standard colorectal cancer protocols).
(* While variants of BRCA1, BRCA2 and PALB2 will be detected in the APGI study, only pathological mutations will be included in the homologous recombinant defects phenotype)
4. For HER2 positive patients adequate cardiac function, defined as Left Ventricular Ejection fraction (LVEF) which equals 50% or above the ULN for the institution (whichever is lower). Cardiac function should be assessed within 3 months prior to registration;
5. Have a life expectancy of over 3 months;
6. Performance status of ECOG 0- 2;
7. Patients must have measurable disease (per RECIST 1.1) or evaluable non-measureable disease when lesions below the limits defined for measurable disease by RECIST 1.1. The CT scan should be conducted within 2 weeks of planned treatment commencement.
8. Adequate bone marrow function with platelets which equal or are greater than 100 x 109/L, neutrophils which equal or are greater than 1.5 x 109/L and haemoglobin which equal or are greater than 9.0 g/dL;
9. Adequate renal function (with calculated creatinine clearance greater than 50 ml/min based on the Cockcroft-Gault method, 24hour urine or GFR scan) and serum creatinine which equal or is less than 1.5 x Upper Limit of Normal range (ULN);
10. Adequate hepatic function with serum total bilirubin which equal or are less than 1.5 x upper limit of normal range and ALT/AST which equal or are less than 2.5x upper limit of normal range (or less than 5.0 times ULN with documented liver metastases), alkaline phosphatase which equal or are less than 5x upper limit of normal range, and INR which equal or are less than 1.5;
11. No prior evidence of underlying abnormality in coagulation parameters. Patients who are therapeutically treated with heparin will be allowed to participate provided there are adequate coagulation parameters. Patients who are on warfarin will be allowed to participate provided they are on low molecular weight heparin prior to starting study treatment.
12. Study treatment both planned and able to start within 7 days of registration. If a PICC or portacath is required for treatment, an extra 7 days will be allowed to facilitate this.
13. Signed, written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Contraindications to any study treatments;
2. Prior systemic treatment for recurrent / metastatic disease except for patients with the HER2 positive or antiEGFR responsive target molecular signature. In patients with these molecular signatures, up to one cycle of standard dose gemcitabine +/- abraxane chemotherapy commenced within 5 weeks prior to registration to the study. (For patients receiving an initial cycle of gemcitabine +/- abraxane, they must be considered still suitable for ongoing chemotherapy at standard doses by their responsible clinician.
3. Patients who have received neoadjuvant or adjuvant chemotherapy with gemcitabine +/- abraxane, including chemoradiation, following surgical resection of pancreatic cancer and completed treatment within the last 6 months, unless further treatment with gemcitabine or abraxane is appropriate in the opinion of the treating clinician;
4. Untreated brain metastases or leptomeningeal disease. Patients with brain metastases that have been treated, and are asymptomatic, and have been stable for 3 or more months after treatment are allowed. A baseline CT brain or MRI is only required if there is clinical suspicion of central nervous system involvement;
5. History of another malignancy within 5 years prior to registration. Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, curatively treated cervical carcinoma in situ or non-melanomatous carcinoma of the skin or superficial transitional cell carcinoma of the bladder are eligible. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 5 years after definitive primary treatment;
6. Any significant active infection, including chronic active hepatitis B, hepatitis C, or HIV. Testing for these is not mandatory unless clinically indicated. Patients with known Hepatitis B/C infection will be allowed to participate providing evidence of viral suppression has been documented and the patient remains on appropriate anti-viral therapy;
7. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol;
8. Pregnancy, lactation, or inadequate contraception. Women must be post menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 14 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception.

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)
The process of enrolling an eligible patient to participate in the study is a process that involves registration. The registration process is used to confirm patient eligibility, confirm the personalised treatment arm and assign a unique study ID
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
31/10/2012
Actual
14/11/2013
Date of last participant enrolment
Anticipated
Actual
15/07/2015
Date of last data collection
Anticipated
Actual
Sample size
Target
10
Accrual to date
Final
2
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 1770 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 1771 0
Bankstown-Lidcombe Hospital - Bankstown
Recruitment hospital [3] 1772 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 9699 0
2065 - St Leonards
Recruitment postcode(s) [2] 9700 0
2050 - Camperdown
Recruitment postcode(s) [3] 9701 0
2200 - Bankstown

Funding & Sponsors
Funding source category [1] 285536 0
Other Collaborative groups
Name [1] 285536 0
Sydney Catalyst
Country [1] 285536 0
Australia
Primary sponsor type
Other Collaborative groups
Name
The Australasian Gastro-Intestinal Trials Group (AGITG)
Address
GI CANCER Institute
Locked Bag 77
Camperdown NSW 1450
Country
Australia
Secondary sponsor category [1] 284377 0
None
Name [1] 284377 0
Address [1] 284377 0
Country [1] 284377 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287557 0
Cancer Institute Clinical Human Research Ethics Committee
Ethics committee address [1] 287557 0
Australian Technology Park
Level 9, 8 Central Avenue
EVELEIGH NSW 2015
Ethics committee country [1] 287557 0
Australia
Date submitted for ethics approval [1] 287557 0
16/07/2012
Approval date [1] 287557 0
Ethics approval number [1] 287557 0
Ethics committee name [2] 290235 0
Sydney Local Health District HREC
Ethics committee address [2] 290235 0
Missenden Road
Camperdown NSW 2050
Ethics committee country [2] 290235 0
Australia
Date submitted for ethics approval [2] 290235 0
20/05/2013
Approval date [2] 290235 0
17/06/2013
Ethics approval number [2] 290235 0
HREC/13/RPA/227

Summary
Brief summary
This study aims to determine the feasibility of a personalised treatment strategy, on the basis of a tumour molecular signature via genomic sequencing and protein expression, in patients with advanced recurrent or metastatic pancreatic adenocarcinoma. Who is it for? You may be eligible to join this study if you are aged 18 years or above, with histologically confirmed primary adenocarcinoma of the pancreas, and have one of the following three molecular signatures: 1. HER2 positive (HER2/neu amplification) subgroup 2. Homologous recombinant defects (BRCA1/BRCA2 or PALB2 mutation) subgroup 3. antiEGFR responsive sub-group (KRAS wildtype or KRAS codon13 mutation) Study details Ten patients will be enrolled in a feasibility stage to determine the technical feasibility of enrolling patients to a personalised treatment approach (including the logistics of recruitment, delivery of personalised treatment and general trial conduct). Recruitment to the HER2 positive subgroup will be reviewed after 1 patient has received personalised treatment. Personalised treatment based on genetic signature will comprise of the following: 1. HER2 positive sub-group - gemcitabine 1000mg/m2 over 30 minutes, given intravenously on days 1, 8 & 15 every 28 days until progression or unacceptable toxicity plus trastuzumab 4mg/kg intravenously day 1 only, followed by trastuzumab 2mg/kg given intravenously day 8, then weekly every subsequent week until progression or unacceptable toxicity or a total of 6 months treatment is completed. 2. Homologous recombinant defects subgroup - gemcitabine 1000mg/m2 over 30 minutes, given intravenously on days 1, 8 & 15 every 28 days until progression or unacceptable toxicity plus cisplatin 50 mg/m2 given intravenously over 60 minutes on days 1& 15 every 28 days until progression or unacceptable toxicity 3. antiEGFR responsive sub-group - gemcitabine 1000mg/m2 given intravenously days 1,8 & 15 each 28 day cycle until progression or unacceptable toxicity plus erlotinib 100mg orally daily continuously until progression or unacceptable toxicity Note: Patients may have received up to one cycle of standard gemcitabine treatment or gemcitabine in combination with abraxane prior to personalised treatment Patients will be evaluated at least 4 weekly to see how they are responding to treatment until progression, unacceptable toxicity or a total of 6 months treatment is completed.


Trial website
http://www.sydneycatalyst.org.au/
Trial related presentations / publications
Nil to date
Public notes

Contacts
Principal investigator
Name 34374 0
Dr Lorraine Chantrill
Address 34374 0
Kinghorn Cancer Centre
Level 10
370 Victoria Street, Darlinghurst
NSW 2010
Country 34374 0
Australia
Phone 34374 0
+ 61 2 9355 5600
Fax 34374 0
Email 34374 0
[email protected]
Contact person for public queries
Name 17621 0
Dr IMPACT Project Manager
Address 17621 0
NHMRC Clinical Trials Centre
Locked Bag 77
Camperdown NSW 1450
Country 17621 0
Australia
Phone 17621 0
+61 2 9562 5000
Fax 17621 0
+61 2 9562 5094
Email 17621 0
[email protected]
Contact person for scientific queries
Name 8549 0
Dr IMPACT Project Manager
Address 8549 0
NHMRC Clinical Trials Centre
Locked Bag 77
Camperdown NSW 1450
Country 8549 0
Australia
Phone 8549 0
+61 2 9562 5000
Fax 8549 0
+61 2 9562 5094
Email 8549 0
[email protected]

No information has been provided regarding IPD availability


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
EmbasePrecision medicine for advanced pancreas cancer: The individualized molecular pancreatic cancer therapy (IMPaCT) Trial.2015https://dx.doi.org/10.1158/1078-0432.CCR-15-0426
EmbasePancreatic cancer: Optimizing treatment options, new, and emerging targeted therapies.2015https://dx.doi.org/10.2147/DDDT.S60328
Dimensions AIPersonalising pancreas cancer treatment: When tissue is the issue2014https://doi.org/10.3748/wjg.v20.i24.7849
N.B. These documents automatically identified may not have been verified by the study sponsor.