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

Rectal Cancer Clinical Trial

— EXCITE  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00972881
• Other study ID #: CDR0000648171
• Secondary ID: CRUK-UCL-EXCITEE
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 5, 2009
• Last updated: October 24, 2017
• Start date: April 2009
• Est. completion date: December 31, 2016

Study information

• Verified date: December 2014
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: December 31, 2016
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

Biological:
• cetuximab

Drug:
• capecitabine

• irinotecan hydrochloride

Procedure:
• neoadjuvant therapy

• therapeutic conventional surgery

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United Kingdom	Yorkshire Regional Clinical Trials & Research Unit	Leeds	England
United Kingdom	Christie Hospital	Manchester	England
United Kingdom	Clatterbridge Centre for Oncology	Merseyside	England
United Kingdom	Rosemere Cancer Centre at Royal Preston Hospital	Preston	England
United Kingdom	Cancer Research UK and University College London Cancer Trials Centre	Rhyl, Denbighshire	Wales

Sponsors (1)

Lead Sponsor	Collaborator
University College, London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Histologically confirmed R0 resection rate		Week 14 (6 weeks after treatment complete)
Secondary	Radiotherapy compliance	Radiotherapy treatment and dosage is captured on weekly CRFs from week 2-6	Weeks 2, 3, 4, 5 & 6
Secondary	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
Secondary	Pathological complete response		Week 14 (surgery conducted 6 weeks from end of treatment)
Secondary	Post-operative morbidity		Week 14
Secondary	Long-term morbidity		Week 14, then at 6, 12, 24 & 36 months follow up
Secondary	Disease-free survival		Baseline, week 1- 10, week 12, 14 & then at 6, 12, 24 & 36 months follow up
Secondary	Local failure-free survival		Baseline, weeks 1- 10, weeks 12 & 14 then at 6, 12, 24 & 36 months follow up

External Links

•   Clinical trial summary from the Cancer Research UK website