Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612000901808
Ethics application status
Approved
Date submitted
16/08/2012
Date registered
24/08/2012
Date last updated
12/10/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Randomised Phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic colorectal cancer (CRC) with either KRAS WT or G13D mutation.
Scientific title
ICE CREAM: The Irinotecan Cetuximab Evaluation and the Cetuximab Response Evaluation Among Patients with G13D Mutation
Secondary ID [1] 280270 0
NIL
Universal Trial Number (UTN)
Trial acronym
ICE CREAM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic colorectal cancer 286218 0
Condition category
Condition code
Cancer 286434 286434 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Cetuximab & irinotecan combination therapy:
Cetuximab 400mg/m2 Intravenous infusion (IVI) on Day 1, followed by 250mg/m2 Intravenous infusion (IVI) every week;
Irinotecan 180mg/m2 Intravenous infusion (IVI) every 14 days;
Treatment will continue until disease progression, unless there is unacceptable toxicity or either the patient or physician requests cessation of treatment.
Intervention code [1] 284621 0
Treatment: Drugs
Comparator / control treatment
Cetuximab monotherapy
Cetuximab 400mg/m2 Intravenous infusion (IVI) on Day 1, followed by 250mg/m2 IVI every week.
Treatment will continue until disease progression, unless there is unacceptable toxicity or either the patient or physician requests cessation of treatment.
Control group
Active

Outcomes
Primary outcome [1] 286879 0
To determine the 6 month PFS benefit of cetuximab alone or in combination with irinotecan in patients with KRAS WT or KRAS G13D mutated mCRC (PFS defined from time of randomisation to disease progression as defined by RECIST criteria version 1.1).
Timepoint [1] 286879 0
Patients will have a CT scan at baseline and every 6 weeks while on treatment. Patients will be followed up for 12 months after they progress on treatment.
Secondary outcome [1] 296898 0
To determine the response rate in patients with KRAS WT or KRAS G13D mutated mCRC treated with cetuximab alone or in combination with irinotecan (Complete and Partial Responses as defined by RECIST criteria version 1.1).
Timepoint [1] 296898 0
Patients will have a CT scan at baseline and every 6 weeks while on treatment.

Eligibility
Key inclusion criteria
1. Males or females with histologically confirmed colorectal cancer;
2. Age greater than or equal to 18 yrs;
3. Metastatic disease not amenable to complete resection as determined by investigator;
4. Measurable or evaluable disease as assessed by CT scan of the chest, abdomen and pelvis as per the RECIST v1.1 criteria, within 21 days prior to randomisation;
5. Prior confirmation of tumour status as either:
“All RAS WT”, - that is no mutation or changes in either KRAS NRAS
OR
KRAS G13D
by means of mutation or relevant analysis performed on representative samples of diagnostic tumour tissue. Also, in cases where the BRAF tumour status is known there must be no mutation. Representative sample of diagnostic tumour tissue must be available for retrospective mutational analysis at a central laboratory.
6. ECOG performance status of 0-1;
7. Received and progressed on, or intolerant of all therapies listed below, where failure is defined as radiological progression during therapy, or toxicity limiting further therapy, or progression within 6 months of prior treatment. Previous treatment should have ceased at least 14 days prior to randomisation.
- thymidylate synthase inhibitor (e.g. 5-fluorouracil, capecitabine, raltitrexed, tegafur-uracil, S1) Thymidylate synthase inhibitors may have been given as monotherapy, or in combination with oxaliplatin or irinotecan
- irinotecan-containing regimen (ie. single agent or in combination and still able to tolerate additional irinotecan treatment);
- oxaliplatin-containing regimen, OR have documented unsuitability for an oxaliplatin-containing regimen;
8. Adequate haematological and renal function as determined by the investigator within 14 days prior to randomization
- Platelets greater than or equal to 75 x 10 to the power of 9/L, Hemoglobin greater than or equal to 80 g/L, ANC greater than or equal to 1.0 x 10 to the power of 9/L
- Serum creatinine less than or equal to 1.5 x institutional upper limit of normal or Creatinine Clearance greater than 50 ml/min
9. Adequate liver function with serum total bilirubin less than or equal to 2.5 x ULN, and both ALT and AST are less than or equal to 5.0 x ULN, within 14 days prior to randomization. Patients with Gilbert’s syndrome may be included as long as unconjugated bilirubin levels fall within these parameters;
10. Life expectancy of at least 12 weeks;
11. Study treatment both planned and able to start within 14 days of randomisation;
12. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments;
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. Prior treatment with cetuximab or other drugs targeting the EGFR pathway, such as panitumumab, gefitinib , erlotinib; 2. Severe restrictive lung disease or radiological pulmonary findings of “interstitial lung disease” on the baseline chest CT which, in the opinion of the investigator, represents significant pathology; 3. Brain metastases that are either untreated, symptomatic, or which have not been stable for at least one month after treatment; 4. History of other malignancies except where treated with curative intent AND with no current evidence of disease AND considered not to be at risk of future recurrence; 5. Concurrent illness, including severe infection that may jeopardize the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety; 6. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse; 7. 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 7 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
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The study population will consist of patients with metastatic colorectal cancer with either KRAS WT or KRAS G13D mutation. Once a patient completed all screening procedures and is confirmed eligible the will be randomised to either cetuximab monptherapy ( Arm A) or cetuximab in combination with irinotecan ( Arm B) . Randomisation will either be done via the electronic case report form ( INFORM) or via telephone randomisation with the NHMRC clinical trials centre.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Treatment will be allocated using the minimization method, patients will be stratified by KRAS status : KRAS WT vs KRAS G13D and site.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
13/11/2012
Actual
13/11/2012
Date of last participant enrolment
Anticipated
20/04/2016
Actual
20/04/2016
Date of last data collection
Anticipated
Actual
13/07/2017
Sample size
Target
100
Accrual to date
Final
101
Recruitment in Australia
Recruitment state(s)
NSW,VIC,QLD,SA,WA,TAS
Recruitment outside Australia
Country [1] 4237 0
United Kingdom
State/province [1] 4237 0
London
Country [2] 4238 0
Spain
State/province [2] 4238 0
Barcelona
Country [3] 5156 0
Italy
State/province [3] 5156 0
Napoli

Funding & Sponsors
Funding source category [1] 285036 0
Commercial sector/Industry
Name [1] 285036 0
Merck Serono
Country [1] 285036 0
Australia
Primary sponsor type
Other Collaborative groups
Name
AGITG
Address
NHMRC Clinical Trials Centre,
Level 5, 92-94 Parramatta Rd
Camperdown,
NSW
2050
Country
Australia
Secondary sponsor category [1] 283898 0
None
Name [1] 283898 0
Address [1] 283898 0
Country [1] 283898 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287040 0
Cancer Institute NSW
Ethics committee address [1] 287040 0
PO BOX 41
Alexandria 2015
Ethics committee country [1] 287040 0
Australia
Date submitted for ethics approval [1] 287040 0
10/04/2012
Approval date [1] 287040 0
02/08/2012
Ethics approval number [1] 287040 0
Ethics committee name [2] 295067 0
SLHD Ethics Review Committee RPAH Zone
Ethics committee address [2] 295067 0
RPAH Medical Centre
Suite 210A, 100 Carillon Avenue
NEWTOWN NSW 2042
Ethics committee country [2] 295067 0
Australia
Date submitted for ethics approval [2] 295067 0
05/06/2013
Approval date [2] 295067 0
12/07/2013
Ethics approval number [2] 295067 0
X13-0176

Summary
Brief summary
Who is it for?
You can join this study if you have metastatic colorectal cancer and have either a KRAS wild type or KRAS G13D mutation

Trial details:
Patients that pass all screening assessments, including CT scan and blood test will randomly divided into two groups. One group wiil receive cetuximab alone ( Arm A) and the other group will receive cetuximab in combination with irinotecan ( Arm B). In both groups, the chemotherapy is given intravenously. Cetuximab is administered weekly to both groups and patients in Arm B will receive irinotecan every 14 days. The study aims to evaluate the response to the different therapy regimens, by looking at the response on CT scans, survival rates and quality of life.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34017 0
A/Prof Eva Segelov
Address 34017 0
NHMRC Clinical Trials Centre
University of Sydney
Locked Bag 77 Camperdown NSW 1450
Country 34017 0
Australia
Phone 34017 0
+61 2 9562 5000
Fax 34017 0
+61 2 9562 5094
Email 34017 0
[email protected]
Contact person for public queries
Name 17264 0
Prof ICECREAM Trial Coordinator
Address 17264 0
NHMRC Clinical Trials Centre
University of Sydney
Locked Bag 77
Camperdown
NSW
1450
Country 17264 0
Australia
Phone 17264 0
+61 2 9562 5000
Fax 17264 0
+61 2 9562 5094
Email 17264 0
[email protected]
Contact person for scientific queries
Name 8192 0
Prof ICECREAM Trial Coordinator
Address 8192 0
NHMRC Clinical Trials Centre
University of Sydney
Locked Bag 77
Camperdown
NSW
1450
Country 8192 0
Australia
Phone 8192 0
+61 2 9562 5000
Fax 8192 0
+61 2 9562 5094
Email 8192 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
EmbaseICECREAM: Randomised phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic colorectal cancer with either KRAS, NRAS, BRAF and PI3KCA wild type, or G13D mutated tumours.2016https://dx.doi.org/10.1186/s12885-016-2389-8
EmbaseStrategies to tackle RAS-mutated metastatic colorectal cancer.2021https://dx.doi.org/10.1016/j.esmoop.2021.100156
N.B. These documents automatically identified may not have been verified by the study sponsor.