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

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)

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.

Study Overview

• Status: Completed
• Conditions: Rectal Cancer
• Intervention / Treatment: Drug: irinotecan hydrochloride; Radiation: radiation therapy; Procedure: therapeutic conventional surgery; Procedure: neoadjuvant therapy; Drug: capecitabine; Biological: cetuximab

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).

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • England
    • Leeds, England, United Kingdom, LS16 6QB
      • Yorkshire Regional Clinical Trials & Research Unit
    • Manchester, England, United Kingdom, M20 4BX
      • Christie Hospital
    • Merseyside, England, United Kingdom, CH63 4JY
      • Clatterbridge Centre for Oncology
    • Preston, England, United Kingdom, PR2 9HT
      • Rosemere Cancer Centre at Royal Preston Hospital
  • Wales
    • Rhyl, Denbighshire, Wales, United Kingdom, LL 18 5UJ
      • Cancer Research UK and University College London Cancer Trials Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Histologically confirmed R0 resection rate	Week 14 (6 weeks after treatment complete)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiotherapy compliance	Radiotherapy treatment and dosage is captured on weekly CRFs from week 2-6	Weeks 2, 3, 4, 5 & 6
Grade 3 or 4 toxicity as assessed by NCI CTCAE v3.0	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.	Baseline, week 1- 10, week 12 & 14 then at 6, 12, 24 & 36 months follow up
Pathological complete response		Week 14 (surgery conducted 6 weeks from end of treatment)
Post-operative morbidity		Week 14
Long-term morbidity		Week 14, then at 6, 12, 24 & 36 months follow up
Disease-free survival		Baseline, week 1- 10, week 12, 14 & then at 6, 12, 24 & 36 months follow up
Local failure-free survival		Baseline, weeks 1- 10, weeks 12 & 14 then at 6, 12, 24 & 36 months follow up

Collaborators and Investigators

• Sponsor: University College, London
• Investigators: Principal Investigator: Simon Gollins, MD, Glan Clwyd Hospital

Publications and helpful links

Helpful Links

• Clinical trial summary from the Cancer Research UK website

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 31, 2016

Study Registration Dates

• First Submitted: September 5, 2009
• First Submitted That Met QC Criteria: September 5, 2009
• First Posted (Estimate): September 9, 2009

Study Record Updates

• Last Update Posted (Actual): October 25, 2017
• Last Update Submitted That Met QC Criteria: October 24, 2017
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; Locally advanced rectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Topoisomerase I Inhibitors; Capecitabine; Irinotecan; Cetuximab
• Other Study ID Numbers: CDR0000648171; CRUK-UCL-EXCITE; EUDRACT-2007-006701-25; EU-20964