Capecitabine, Irinotecan Hydrochloride, Cetuximab, and Radiation Therapy in Treating Patients Undergoing Surgery for Locally Advanced Rectal Cancer (EXCITE)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT00972881
First received: September 5, 2009
Last updated: April 5, 2013
Last verified: April 2013
  Purpose

RATIONALE: Drugs used in chemotherapy, such as capecitabine and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy, cetuximab, and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase I/II trial is studying the side effects of giving capecitabine and irinotecan hydrochloride together with cetuximab and radiation therapy and to see how well it works in treating patients undergoing surgery for locally advanced rectal cancer.


Condition Intervention Phase
Rectal Cancer
Biological: cetuximab
Drug: capecitabine
Drug: irinotecan hydrochloride
Procedure: neoadjuvant therapy
Procedure: therapeutic conventional surgery
Radiation: radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: EXCITE: Erbitux, Xeloda, Campto, Irradiation Then Excision for Locally Advanced Rectal Cancer (North West Clinical Oncology Group-04 on Behalf of the NCRI Rectal Cancer Subgroup)

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • Histologically confirmed R0 resection rate [ Time Frame: Week 14 (6 weeks after treatment complete) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Radiotherapy compliance [ Time Frame: Weeks 2, 3, 4, 5 & 6 ] [ Designated as safety issue: No ]
    Radiotherapy treatment and dosage is captured on weekly CRFs from week 2-6

  • Grade 3 or 4 toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: Baseline, week 1- 10, week 12 & 14 then at 6, 12, 24 & 36 months follow up ] [ Designated as safety issue: Yes ]
    Adverse events are recorded weekly on CRFs from week 1 of treatment until 4 weeks post treatment, then at 1 month post surgery and specified time points during long term follow up at 6, 12, 24 & 36 month intervals.

  • Pathological complete response [ Time Frame: Week 14 (surgery conducted 6 weeks from end of treatment) ] [ Designated as safety issue: No ]
  • Post-operative morbidity [ Time Frame: Week 14 ] [ Designated as safety issue: No ]
  • Long-term morbidity [ Time Frame: Week 14, then at 6, 12, 24 & 36 months follow up ] [ Designated as safety issue: No ]
  • Disease-free survival [ Time Frame: Baseline, week 1- 10, week 12, 14 & then at 6, 12, 24 & 36 months follow up ] [ Designated as safety issue: No ]
  • Local failure-free survival [ Time Frame: Baseline, weeks 1- 10, weeks 12 & 14 then at 6, 12, 24 & 36 months follow up ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: April 2009
Estimated Study Completion Date: December 2014
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • To assess the downstaging effectiveness and tolerability of neoadjuvant chemoradiotherapy comprising capecitabine, irinotecan hydrochloride, cetuximab, and radiotherapy in patients with locally advanced rectal cancer.

OUTLINE: This is a multicenter study.

Patients receive cetuximab IV over 1-2 hours once weekly in weeks 1-6 and irinotecan hydrochloride IV over 1 hour once weekly in weeks 2-5. Patients also undergo pelvic radiotherapy once daily and receive oral capecitabine twice daily on days 1-5 in weeks 2-6.

Patients undergo surgery 8 weeks after completion of chemoradiotherapy.

After completion of study treatment, patients are followed up at 6, 12, 24, and 36 months.

Peer Reviewed and Funded or Endorsed by Cancer Research United Kindom (UK).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma of the rectum
  • MRI-defined locally advanced disease, as defined by 1 of the following:

    • Mesorectal fascia involvement
    • Mesorectal fascia threatened (tumor ≤ 1 mm from mesorectal fascia)
    • Any T3 tumor < 5 cm from anal verge
  • No evidence of metastatic disease

PATIENT CHARACTERISTICS:

  • ECOG or WHO performance status 0-1
  • ANC ≥ 1.5 x 10^9/L
  • Platelet count ≥ 100 x 10^9/L
  • Serum bilirubin < 1.25 times upper limit of normal (ULN)
  • Serum transaminase(s) < 3 times ULN
  • Serum alkaline phosphatase < 5 times ULN
  • Estimated glomerular filtration rate > 50 mL/min
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • Fit to receive all study treatments
  • Able to comply with oral medication
  • No comorbidity or coagulation problem that would deem the patient unsuitable for surgery
  • No pre-existing condition that would preclude radiotherapy (e.g., fistulas, severe ulcerative colitis [particularly patients currently taking sulfasalazine], Crohn's disease, prior adhesions)
  • No current or impending rectal obstruction (unless a defunctioning stoma is present) or metallic colonic rectal stent in situ
  • No significant small bowel delineated within the radiotherapy fields
  • No pelvic sepsis
  • No gastrointestinal disorder that would interfere with oral therapy or oral bioavailability
  • No uncontrolled cardiac, respiratory, or other disease that would preclude study therapy or informed consent
  • No serious medical or psychiatric disorder that would preclude study therapy or informed consent
  • No known dihydropyrimidine dehydrogenase deficiency

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy
  • No prior radiotherapy to the pelvis
  • No concurrent participation in other studies, except genetic studies (e.g., NSCCG-National Study of Colorectal Cancer Genetics)
  • No concurrent St. John wort
  • No other concurrent cytotoxic treatment or radiotherapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00972881

Locations
United Kingdom
Yorkshire Regional Clinical Trials & Research Unit
Leeds, England, United Kingdom, LS16 6QB
Christie Hospital
Manchester, England, United Kingdom, M20 4BX
Clatterbridge Centre for Oncology
Merseyside, England, United Kingdom, CH63 4JY
Rosemere Cancer Centre at Royal Preston Hospital
Preston, England, United Kingdom, PR2 9HT
Cancer Research UK and University College London Cancer Trials Centre
Rhyl, Denbighshire, Wales, United Kingdom, LL 18 5UJ
Sponsors and Collaborators
University College, London
Investigators
Principal Investigator: Simon Gollins, MD Glan Clwyd Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT00972881     History of Changes
Other Study ID Numbers: CDR0000648171, CRUK-UCL-EXCITE, EUDRACT-2007-006701-25, EU-20964
Study First Received: September 5, 2009
Last Updated: April 5, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University College, London:
adenocarcinoma of the rectum
Locally advanced rectal cancer

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Irinotecan
Camptothecin
Capecitabine
Cetuximab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on August 28, 2014