Clinical trial NCT00972881: Capecitabine, Irinotecan Hydrochloride, Cetuximab, and Radiation Therapy in Treating Patients Undergoing Surgery for Locally Advanced Rectal Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Rectal Cancer
Keywords: adenocarcinoma of the rectum
Locally advanced rectal cancer
Lead sponsor: University College, London
Sponsor class: OTHER
First posted: 2009-09-09
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility 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

Primary outcomes:
measure: Histologically confirmed R0 resection rate
timeFrame: Week 14 (6 weeks after treatment complete)
Secondary outcomes:
measure: Radiotherapy compliance
timeFrame: Weeks 2, 3, 4, 5 & 6
measure: Grade 3 or 4 toxicity as assessed by NCI CTCAE v3.0
timeFrame: Baseline, week 1- 10, week 12 & 14 then at 6, 12, 24 & 36 months follow up
measure: Pathological complete response
timeFrame: Week 14 (surgery conducted 6 weeks from end of treatment)
measure: Post-operative morbidity
timeFrame: Week 14
measure: Long-term morbidity
timeFrame: Week 14, then at 6, 12, 24 & 36 months follow up
measure: Disease-free survival
timeFrame: Baseline, week 1- 10, week 12, 14 & then at 6, 12, 24 & 36 months follow up
measure: Local failure-free survival
timeFrame: Baseline, weeks 1- 10, weeks 12 & 14 then at 6, 12, 24 & 36 months follow up
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: Yorkshire Regional Clinical Trials & Research Unit
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital
state: England
city: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology
state: England
city: Preston
country: United Kingdom
facility: Rosemere Cancer Centre at Royal Preston Hospital
state: England
city: Rhyl, Denbighshire
country: United Kingdom
facility: Cancer Research UK and University College London Cancer Trials Centre
state: Wales
Study officials:
affiliation: Glan Clwyd Hospital
name: Simon Gollins, MD
role: PRINCIPAL_INVESTIGATOR
References: