• ICECREAM
    Share

Trial Status

Completed

Cancer Type

Colorectal Cancer

Protocol Title

ICECREAM: The Irinotecan Cetuximab Evaluation and the Cetuximab Response Evaluation Among Patients with G13D Mutation.

Randomised Phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic CRC with either KRAS WT or G13D mutation.

Purpose of the Study

The ICECREAM study aimed to provide important data on the optimal use of currently available therapeutics in patients with metastatic colorectal cancer who have progressed on standard chemotherapy options. The trial was designed to answer two questions in parallel.

The goal of the ICECREAM trial was to investigate and evaluate whether cetuximab should be given alone or in combination with chemotherapy in KRAS wild-type patients. The same treatment option will also be studied in patients with the KRAS G13D mutation. The study design would allow KRAS G13D mutated colorectal cancer patients to have access to treatment that is currently unavailable in Australia.

The ICECREAM trial has helped researchers answer an important health question. It has provided evidence that cetuximab alone is not an effective treatment for tumours with the G13D mutation.

Key Eligibility Criteria

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. Life expectancy of at least 12 weeks;
  5. Study treatment both planned and able to start within 14 days of randomisation;
  6. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments;
  7. Signed, written informed consent;

Exclusion Criteria

  1. Prior treatment with cetuximab or other drugs targeting the EGFR pathway
  2. Severe restrictive lung disease
  3. Brain metastases that are either untreated, symptomatic, or which have not been stable for at least one month after treatment;
  4. Concurrent illness, including severe infection
  5. Presence of any psychological, familial, sociological or geographical condition
  6. 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.

More Information

More information available online at the Australian New Zealand Clinical Trial Registry (ANZCTR) here.

Principal Investigator

Prof Eva Segelov

Funding

Merck Serono

Trial Status

Completed

Cancer Type

Colorectal Cancer

Protocol Title

Randomised Phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic CRC with either KRAS WT or G13D mutation.

ICECREAM: The Irinotecan Cetuximab Evaluation and the Cetuximab Response Evaluation Among Patients with G13D Mutation.

Publication Reference

  1. Segelov E, Thavaneswaran S, Waring PM, Desai J, Robledo KP, Gebski VJ, Elez E, Nott LM, Karapetis CS, Lunke S, Chantrill LA, Pavlakis N, Khasraw M, Underhill C, Ciardiello F, Jefford M, Wasan H, Haydon A, Price TJ, van Hazel G, Wilson K, Simes J, Shapiro JD. Response to cetuximab with or without irinotecan in patients with refractory metastatic colorectal cancer harboring the KRAS G13D mutation: Australasian Gastro-Intestinal Trials Group ICECREAM Study. Journal of Clinical Oncology 2016; 34(19): 2258–2264.
  2. Segelov E, Waring P, Desai J, Wilson K, Gebski V, Thavaneswaran S, Elez E, Underhill C, Pavlakis N, Chantrill L, Nott L, Jefford M, Khasraw M, Day F, Wasan H, Ciardiello F, Karapetis C, Joubert W, van Hazel G, Haydon A, Price T, Tejpar S, Tebbutt N, Shapiro J. ICECREAM: 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. BMC Cancer 2016; 16: 339.

Conference Presentation Reference

  1. Shapiro JD, Thavaneswaran S, Underhill C, Robledo KP, Karapetis CS, Day FL, Nott LM, M. J, Chantrill LA, Pavlakis N, Tebbutt NC, Price TJ, Khasraw M, Van Hazel G, Waring PM, Tejpar S, Simes J, Gebski V, Desai J, Segelov E. Results of the quad wild type arm of the AGITG ICECREAM study: a randomised phase II study of cetuximab alone or in combination with irinotecan in patients with refractory metastatic colorectal cancer with no mutations in KRAS, NRAS, BRAF or PIK3CA. American Society of Oncology Annual Meeting; 2–6 Jun 2017; Chicago.
  2. Segelov E, Thavaneswaran S, Waring P, Desai J, Mann K, Elez E, Chantrill L, Pavlakis N, Nott L, Underhill C, Khasraw M, Wasan H, Ciardiello F, Jefford M, Joubert W, Haydon A, Karapetis C, Price T, Wilson K, Shapiro J. AGITG ICECREAM study: the Irinotecan Cetuximab Evaluation and Cetuximab Response Evaluation Amongst Patients with a G13D Mutation: analysis of outcomes in patients with refractory metastatic colorectal cancer harbouring the KRAS G13D mutation. European Cancer Congress 2015; 25-29 Sep 2015; Vienna.
  3. Segelov E, Wilson K, Gebski V, Waring P, Tabernero J, Wasan H, Ciardiello F, Desai J, Underhill C, Karapetis C, Khasraw M, Nott L, Joubert W, Pavlakis M, Van Hazel G, Chantrill L, Price T, Jefford M, Haydon A, Shapiro J. ICE CREAM: Irinotecan cetuximab evaluation and the cetuximab response evaluation among patients with G13D mutation. American Society of Clinical Oncology Annual Meeting; 31 May–4 Jun 2013; Chicago. Journal of Clinical Oncology; 31(suppl.): TPS3649.
  4. Segelov E, Wilson K, Gebski V, Waring P, Desai J, Nott L, Karapetis C, Hall M, Wasan H, Shapiro J. ICECREAM: irinotecan cetuximab evaluation and the cetuximab response evaluation among patients with G13D mutation. Clinical Oncological Society of Australia 40th Annual Meeting; 12-14 Nov 2013; Adelaide. Asia-Pacific Journal of Clinical Oncology 2013; S3: 155.

AIM

The ICECREAM study aims to compare the efficacy of cetuximab alone or in combination with irinotecan in patients with KRAS WT or KRAS G13D mutated metastatic colorectal cancer who have progressed on prior oxaliplatin and irinotecan based chemotherapy.

Background

Previous studies by the Australasian Gastro-intestinal Trials Group (AGITG) have demonstrated that cetuximab, an EFGR monoclonal antibody, prolongs survival in patients with metastatic colorectal cancer refractory to all other chemotherapy. Some medical practitioners believe that combining this treatment with irinotecan will achieve better results due to the results of one UK trial that reported modest increases in tumour shrinkage and control of the disease. However, there were greater side effects and survival was not increased on this study.

Soon after the initial cetuximab clinical trials were reported, the AGITG and other groups showed that cetuximab was not effective in people who had the specific abnormality (mutation called a KRAS Gene Mutation) in their colon cancer cells. Up to 40% of patients have this abnormality, which can be easily tested, and only patients without this mutation (KRAS wild-type) are given this treatment. When restricted to this subgroup, the benefits of cetuximab are significantly enhanced.

The picture has become more complicated recently with further research showing patients with a particular type of KRAS mutation (G13D) may actually benefit from cetuximab treatment. Currently, cetuximab is US FDA and Australian TGA approved only for patients without any KRAS mutation (KRAS wild-type).

This ICECREAM study aims to evaluate whether cetuximab should be given alone or in combination with irinotecan chemotherapy in KRAS wild-type patients in whom the disease has progressed despite previous treatment with oxaliplatin and irinotecan chemotherapy. The data on the effect of cetuximab on patients with G13D KRAS mutation was presented and published in 2016.

Clinical Trial Design

ICECREAM is a phase II, open label, randomised multi-centre trial. Eligible patients with either the KRAS wildtype gene or KRAS G13D mutation will be randomised into two groups to receive either cetuximab alone or the combination of cetuximab and irinotecan chemotherapy. One group will receive cetuximab alone and the other group will receive cetuximab in combination with irinotecan. In both groups the treatment will be administered intravenously. Cetuximab is administered weekly to both groups and patients in combination therapy group will receive irinotecan every 14 days.

The study will monitor the patients and evaluate the response to the different treatment plans, by looking at the response on CT scans, survival rates and quality of life. Treatment will continue until disease progression, unacceptable toxicity or either the patient or the physician requests treatment to end.

Study Chairs

Professor Eva Segelov (Monash Health, Monash University, Melbourne VIC)
Associate Professor Jeremy Shapiro (Cabrini Haematology & Oncology Centre, Malvern VIC)

Contact Email

icecream@ctc.usyd.edu.au

Principal Investigator

Professor Eva Segelov

More Information

Available online at the Australian New Zealand Clinical Trial Registry (ANZCTR) here.

Funding

Merck Serono