Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT00383695
Other study ID # CDR0000503948
Secondary ID RMNHS-RMH-CCR-25
Status Active, not recruiting
Phase Phase 2
First received September 29, 2006
Last updated January 12, 2010
Start date September 2005

Study information

Verified date January 2010
Source Royal Marsden NHS Foundation Trust
Contact n/a
Is FDA regulated No
Health authority United Kingdom: Medicines and Healthcare Products Regulatory Agency
Study type Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. 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. Giving chemotherapy and radiation therapy with or without cetuximab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether giving oxaliplatin, capecitabine, and radiation therapy is more effective with or without cetuximab when given before surgery in treating rectal cancer.

PURPOSE: This randomized phase II trial is studying oxaliplatin, capecitabine, and radiation therapy to compare how well they work with or without cetuximab in treating patients undergoing surgery for high-risk rectal cancer.


Description:

OBJECTIVES:

- Compare the pathological complete response rate at total mesorectal excision in patients with high-risk rectal cancer treated with neoadjuvant therapy comprising oxaliplatin, capecitabine, and radiotherapy with or without cetuximab.

OUTLINE: This is a multicenter, open-label, randomized, controlled study. Patients are stratified according to participating center and presence of T4 disease (yes vs no). Patients are randomized to 1 of 2 treatment arms.

- Arm I:

- Neoadjuvant chemotherapy: Patients receive oxaliplatin IV over 2 hours on days 1, 22, 43, and 64 and oral capecitabine twice daily on days 1-14, 22-35, 43-56, and 64-77.

- Neoadjuvant chemoradiotherapy: Patients undergo radiotherapy once daily on days 85-89, 92-96, 99-103, 106-110, 113-117, and 120-124 and receive oral capecitabine twice daily on days 85-126.

- Surgery: Four to six weeks after completion of chemoradiotherapy, patients undergo total mesorectal excision (TME).

- Adjuvant therapy: Beginning 6-8 weeks after surgery, patients receive oxaliplatin IV over 2 hours on days 1, 22, 43, and 64 and oral capecitabine twice daily on days 1-14, 22-35, 43-56, and 64-77.

- Arm II:

- Neoadjuvant therapy: Patients receive oxaliplatin and capecitabine as in arm I neoadjuvant chemotherapy and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78.

- Neoadjuvant chemoradiotherapy: Patients undergo radiotherapy and receive capecitabine as in arm I neoadjuvant chemoradiotherapy and cetuximab IV over 1 hour on days 85, 92, 99, 106, 113, and 120.

- Surgery: Four to six weeks after completion of chemoradiotherapy patients undergo TME as in arm I.

- Adjuvant therapy: Beginning 6-8 weeks after surgery, patients receive oxaliplatin and capecitabine as in arm I adjuvant chemotherapy and cetuximab IV over 1 hour on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed periodically.

After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually for 2 years.

PROJECTED ACCRUAL: A total of 164 patients will be accrued for this study.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 164
Est. completion date
Est. primary completion date
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma or undifferentiated non-small cell carcinoma of the rectum

- MRI-defined high-risk, operable disease, defined by = 1 of the following:

- Tumors within 1 mm of mesorectal fascia (i.e., circumferential resection margin threatened or involved)

- T3 tumors at or below levators

- Tumors extending = 5 mm into perirectal fat

- T4 tumors

- Presence of extramural venous invasion (primary tumor is therefore at least T3)

- No evidence of metastatic disease by CT scan of the chest and abdomen or, if required, by positron emission tomography scan or biopsy

- No rectal cancer that is unlikely to be operable even after neoadjuvant treatment (i.e., tumor involving the internal iliac vessels)

- No T1-2 rectal cancer, in the absence of other high-risk factors

- T2 tumors within 1 mm of mesorectal fascia allowed

- No recurrent disease

PATIENT CHARACTERISTICS:

- WHO performance status 0-2

- Life expectancy > 3 months

- WBC > 3,000/mm³

- Absolute neutrophil count > 1,500/mm³

- Platelet count > 100,000/mm³

- Bilirubin < 1.5 times upper limit of normal (ULN)

- Transaminases < 2.5 times ULN

- Creatinine normal OR creatinine clearance > 50 mL/min

- Not pregnant or nursing

- Fertile patients must use effective contraception

- No concurrent uncontrolled medical condition

- No other active malignant disease within the past 10 years except nonmelanoma skin cancer or carcinoma in situ of the cervix

- No contraindications to MRI (e.g., pacemaker)

- No medical or psychiatric conditions that would preclude informed consent

- No known malabsorption syndrome or lack of physical integrity of the upper gastrointestinal tract

- No clinically significant (i.e., active) cardiac disease, including any of the following:

- Congestive heart failure

- Symptomatic coronary artery disease

- Cardiac dysrhythmia (e.g., atrial fibrillation, even if controlled with medication)

- Myocardial infarction within the past 12 months

- No symptoms or history of peripheral neuropathy

PRIOR CONCURRENT THERAPY:

- No prior chemotherapy, radiotherapy, or investigational treatment for rectal cancer

- No other concurrent cytotoxic agents or investigational drugs

- No concurrent sorivudine or sorivudine analogues (e.g., brivudine)

Study Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Biological:
cetuximab

Drug:
capecitabine

oxaliplatin

Procedure:
adjuvant therapy

conventional surgery

neoadjuvant therapy

Radiation:
radiation therapy


Locations

Country Name City State
Spain Vall d'Hebron University Hospital Barcelona
Spain Hospital Universitario La Paz Madrid
Spain Hospital Clinico Universitario de Valencia Valencia
Sweden Karolinska University Hospital - Solna Stockholm
Sweden Uppsala University Hospital Uppsala
United Kingdom Royal Bournemouth Hospital NHS Trust Bournemouth England
United Kingdom Sussex Cancer Centre at Royal Sussex County Hospital Brighton England
United Kingdom Eastbourne District General Hospital Eastbourne England
United Kingdom Cancer Research UK Clinical Groups at Guy's King's & St. Thomas' Hospitals London England
United Kingdom Mid Kent Oncology Centre at Maidstone Hospital Maidstone England
United Kingdom Dorset Cancer Centre Poole Dorset England
United Kingdom Southampton General Hospital Southampton England
United Kingdom Royal Marsden - Surrey Sutton England

Sponsors (1)

Lead Sponsor Collaborator
Royal Marsden NHS Foundation Trust

Countries where clinical trial is conducted

Spain,  Sweden,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Pathological complete response rate at time of total mesorectal excision (TME) No
Secondary Radiological response rates after completion of neoadjuvant therapy No
Secondary Complete resection rate (R0 resection) with microscopic clear resection margin (tumor observed > 1 mm from the resection margin), especially circumferential resection margin No
Secondary Perioperative measures, including operation time, duration of in-patient stay, perioperative transfusion requirement, and mortality, within 30 days of TME No
Secondary Postoperative complications, including wound infection, wound dehiscence, and fistula formation No
Secondary Quality of TME as assessed by audit of photographed surgical specimens No
Secondary Rate of abdominoperitoneal excision No
Secondary Rate of permanent defunctioning colostomies No
Secondary Clinical and radiological anastomotic leak rate No
Secondary Progression-free survival and patterns of failure No
Secondary Overall survival No
Secondary Safety Yes
Secondary Quality of life, including long-term bowel function No
See also
  Status Clinical Trial Phase
Recruiting NCT05400122 - Natural Killer (NK) Cells in Combination With Interleukin-2 (IL-2) and Transforming Growth Factor Beta (TGFbeta) Receptor I Inhibitor Vactosertib in Cancer Phase 1
Active, not recruiting NCT05551052 - CRC Detection Reliable Assessment With Blood
Completed NCT00098787 - Bevacizumab and Oxaliplatin Combined With Irinotecan or Leucovorin and Fluorouracil in Treating Patients With Metastatic or Recurrent Colorectal Cancer Phase 2
Recruiting NCT06037954 - A Study of Mental Health Care in People With Cancer N/A
Recruiting NCT05425940 - Study of XL092 + Atezolizumab vs Regorafenib in Subjects With Metastatic Colorectal Cancer Phase 3
Suspended NCT04595604 - Long Term Effect of Trimodal Prehabilitation Compared to ERAS in Colorectal Cancer Surgery. N/A
Completed NCT03414125 - Effect of Mailed Invites of Choice of Colonoscopy or FIT vs. Mailed FIT Alone on Colorectal Cancer Screening N/A
Completed NCT02963831 - A Study to Investigate ONCOS-102 in Combination With Durvalumab in Subjects With Advanced Peritoneal Malignancies Phase 1/Phase 2
Recruiting NCT05489211 - Study of Dato-Dxd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours (TROPION-PanTumor03) Phase 2
Terminated NCT01847599 - Educational Intervention to Adherence of Patients Treated by Capecitabine +/- Lapatinib N/A
Completed NCT05799976 - Text Message-Based Nudges Prior to Primary Care Visits to Increase Care Gap Closure N/A
Recruiting NCT03874026 - Study of Folfiri/Cetuximab in FcGammaRIIIa V/V Stage IV Colorectal Cancer Patients Phase 2
Active, not recruiting NCT03170960 - Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors Phase 1/Phase 2
Completed NCT03167125 - Participatory Research to Advance Colon Cancer Prevention N/A
Completed NCT03181334 - The C-SPAN Coalition: Colorectal Cancer Screening and Patient Navigation N/A
Recruiting NCT04258137 - Circulating DNA to Improve Outcome of Oncology PatiEnt. A Randomized Study N/A
Recruiting NCT05568420 - A Study of the Possible Effects of Medication on Young Onset Colorectal Cancer (YOCRC)
Recruiting NCT02972541 - Neoadjuvant Chemotherapy Verse Surgery Alone After Stent Placement for Obstructive Colonic Cancer N/A
Completed NCT02876224 - Study of Cobimetinib in Combination With Atezolizumab and Bevacizumab in Participants With Gastrointestinal and Other Tumors Phase 1
Completed NCT01943500 - Collection of Blood Specimens for Circulating Tumor Cell Analysis N/A