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

NCT ID: NCT00972881

Last Updated: 2017-10-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2016-12-31

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.

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).

Conditions

Rectal Cancer

Keywords

adenocarcinoma of the rectum; Locally advanced rectal cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

cetuximab

Intervention Type: BIOLOGICAL

capecitabine

Intervention Type: DRUG

irinotecan hydrochloride

Intervention Type: DRUG

neoadjuvant therapy

Intervention Type: PROCEDURE

therapeutic conventional surgery

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University College, London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Simon Gollins, MD

Role: PRINCIPAL_INVESTIGATOR

Glan Clwyd Hospital

Locations

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, United Kingdom

Countries

United Kingdom

Related Links

http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-cetuximab-capecitabine-and-irinotecan-with-radiotherapy-before-surgery-for-cancer-of-the-rectum

Clinical trial summary from the Cancer Research UK website

Other Identifiers

CRUK-UCL-EXCITE

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2007-006701-25

Identifier Type: -

Identifier Source: secondary_id

EU-20964

Identifier Type: -

Identifier Source: secondary_id

CDR0000648171

Identifier Type: -

Identifier Source: org_study_id