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

• ClinicalTrials.gov Identifier: NCT00972881
• Recruitment Status: Completed
• First Posted: September 9, 2009
• Last Update Posted: October 25, 2017
• Sponsor: University College, London
• Information provided by (Responsible Party): University College, London

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Rectal Cancer	Biological: cetuximab; Drug: capecitabine; Drug: irinotecan hydrochloride; Procedure: neoadjuvant therapy; Procedure: therapeutic conventional surgery; Radiation: radiation therapy	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 82 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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)
• Study Start Date: April 2009
• Actual Primary Completion Date: December 2011
• Actual Study Completion Date: December 31, 2016

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. Histologically confirmed R0 resection rate [ Time Frame: Week 14 (6 weeks after treatment complete) ]

Secondary Outcome Measures :

1. Radiotherapy compliance [ Time Frame: Weeks 2, 3, 4, 5 & 6 ]
   Radiotherapy treatment and dosage is captured on weekly CRFs from week 2-6
2. 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 ]
   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.
3. Pathological complete response [ Time Frame: Week 14 (surgery conducted 6 weeks from end of treatment) ]
4. Post-operative morbidity [ Time Frame: Week 14 ]
5. Long-term morbidity [ Time Frame: Week 14, then at 6, 12, 24 & 36 months follow up ]
6. Disease-free survival [ Time Frame: Baseline, week 1- 10, week 12, 14 & then at 6, 12, 24 & 36 months follow up ]
7. Local failure-free survival [ Time Frame: Baseline, weeks 1- 10, weeks 12 & 14 then at 6, 12, 24 & 36 months follow up ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 120 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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:

Clinical trial summary from the Cancer Research UK website 

• Responsible Party: University College, London
• ClinicalTrials.gov Identifier: NCT00972881
• Other Study ID Numbers: CDR0000648171; CRUK-UCL-EXCITE; EUDRACT-2007-006701-25; EU-20964
• First Posted: September 9, 2009
• Last Update Posted: October 25, 2017
• Last Verified: December 2014

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; Capecitabine; Irinotecan; Cetuximab; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Antineoplastic Agents, Immunological