Chemotherapy and Radiation Therapy Before Surgery Followed by Capecitabine With or Without Oxaliplatin in Treating Patients With Locally Advanced Rectal Cancer - Full Text View

Sponsored by:	European Organization for Research and Treatment of Cancer
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00766155

Purpose

RATIONALE: Drugs used in chemotherapy, such as capecitabine and oxaliplatin, 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. Giving radiation therapy that uses a 3-dimensional image of the tumor to help focus thin beams of radiation directly on the tumor may kill more tumor cells and have fewer side effects. Giving chemotherapy together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether capecitabine is more effective with or without oxaliplatin in treating patients with rectal cancer.

PURPOSE: This randomized phase III trial is studying giving chemotherapy together with radiation therapy before surgery followed by capecitabine with or without oxaliplatin to see how well it works in treating patients with locally advanced rectal cancer.

Condition	Intervention	Phase
Colorectal Cancer	Drug: capecitabine Drug: oxaliplatin	Phase III

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Capecitabine Oxaliplatin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label
Official Title:	Preoperative Chemoradiotherapy and Postoperative Chemotherapy With Capecitabine and Oxaplatin vs.Capecitabine Alone in Locally Advanced Rectal Cancer (PETACC-6)

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Disease-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival within at least the first 5 years after treatment [ Designated as safety issue: No ]
Loco-regional failure, defined as local or regional recurrence, inoperable disease, or R1 or R2 resection [ Designated as safety issue: No ]
Distant failure (i.e., distant metastasis) [ Designated as safety issue: No ]
Pathological down-stage (ypT0, 2N0) rate [ Designated as safety issue: No ]
Pathological complete remission (ypT0N0) rate [ Designated as safety issue: No ]
Tumor regression grade [ Designated as safety issue: No ]
Histopathological R0 resection rate [ Designated as safety issue: No ]
Sphincter preservation rate [ Designated as safety issue: No ]
Preoperative complication rate [ Designated as safety issue: No ]
Toxicity according to CTCAE v.3.0 weekly during treatment, at 4-8 weeks after surgery, at therapy completion, and every 6 months for 5 years after therapy completion [ Designated as safety issue: Yes ]

Estimated Enrollment:	1090
Study Start Date:	August 2008

Arms	Assigned Interventions
Arm I: Active Comparator Patients receive oral capecitabine twice daily and undergo concurrent 3-dimensional conformal radiotherapy 5 days a week on days 1-33. Patients may receive additional chemoradiotherapy on days 36-38. Patients then undergo surgery. Beginning 6-8 weeks after surgery, patients receive capecitabine twice daily on day 1-15. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.	Drug: capecitabine Given orally
Arm II: Experimental Patients receive oral capecitabine twice daily and undergo concurrent 3-dimensional conformal radiotherapy 5 days a week on days 1-33. Patients also receive oxaliplatin IV over 1 hour on days 1, 8, 15, 22, and 29 prior to radiotherapy followed by surgery. Patients may receive additional chemoradiotherapy on days 36-38. Beginning 6-8 weeks later, patients receive oxaliplatin IV over 2 hours on day 1, and oral capecitabine twice daily on days 1-15. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.	Drug: capecitabine Given orally Drug: oxaliplatin Given IV

Arms

Assigned Interventions

Arm I: Active Comparator

Patients receive oral capecitabine twice daily and undergo concurrent 3-dimensional conformal radiotherapy 5 days a week on days 1-33. Patients may receive additional chemoradiotherapy on days 36-38. Patients then undergo surgery. Beginning 6-8 weeks after surgery, patients receive capecitabine twice daily on day 1-15. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: capecitabine

Given orally

Arm II: Experimental

Patients receive oral capecitabine twice daily and undergo concurrent 3-dimensional conformal radiotherapy 5 days a week on days 1-33. Patients also receive oxaliplatin IV over 1 hour on days 1, 8, 15, 22, and 29 prior to radiotherapy followed by surgery. Patients may receive additional chemoradiotherapy on days 36-38. Beginning 6-8 weeks later, patients receive oxaliplatin IV over 2 hours on day 1, and oral capecitabine twice daily on days 1-15. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: capecitabine

Given orally

Drug: oxaliplatin

Given IV

Detailed Description:

OBJECTIVES:

Primary

Investigate whether the addition of oxaliplatin to neoadjuvant chemoradiotherapy and adjuvant chemotherapy comprising capecitabine improves disease-free survival in patients with locally advanced rectal cancer.

Secondary

Compare the overall survival of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy and adjuvant chemotherapy comprising capecitabine with versus without oxaliplatin.
Determine the loco-regional failure and distant failure of patients treated with these regimens.
Determine the pathological down-staging (ypT0-2N0) of patients treated with these regimens.
Determine the pathological complete remission (yp T0N0) rate of patients treated with these regimens.
Determine the tumor progression grade and histopathological R0 resection of patients treated with these regimens.
Determine the sphincter preservation rate of patients treated with these regimens.
Determine the perioperative complication rate of these regimens in these patients.
Determine the toxicity of these regimens in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to treating center, clinical T category (T1-3 vs T4), clinical nodal status (Nx vs NO vs N1-2), distance from the tumor to the anal verge (≤ 5 cm vs > 5 cm) and availability of MRI at the center (yes vs no). Patients are randomized to 1 of 2 treatment arms.

Arm I (control):
- Neoadjuvant therapy: Patients receive oral capecitabine twice daily on days 1-35. Patients also undergo concurrent 3-dimensional conformal radiotherapy 5 days a week on days 1-33 followed by surgery. Patients may receive additional chemoradiotherapy on days 36-38.
- Adjuvant therapy: Beginning 6-8 weeks after surgery, patients receive oral capecitabine twice daily on days 1-15. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
Arm II (investigational):
- Neoadjuvant therapy: Patients receive oral capecitabine twice daily and undergo concurrent 3-dimensional conformal radiotherapy 5 days a week on days 1-33. Patients also receive oxaliplatin IV over 1 hour on days 1, 8, 15, 22, and 29 prior to radiotherapy followed by surgery. Patients may receive additional chemoradiotherapy on days 36-38.
- Adjuvant therapy: Beginning 6-8 weeks after surgery, patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-15. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 3 months for 3 years, and then every 6 months for 2 years.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the rectum
- Tumor ≤ 12 cm from the anal verge
- Stage T3-4 or any node-positive disease
No evidence of metastatic disease (confirmed by negative CT scan of the chest and abdomen)
Resectable disease or expected to become resectable after preoperative chemoradiation
May only be randomized once in this trial

PATIENT CHARACTERISTICS:

WHO/ECOG performance status 0-2
Hemoglobin ≥ 10.0 g/dL (transfusion allowed to achieve or maintain levels)
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
ALT and AST ≤ 2.5 times upper level of normal (ULN)
Alkaline phosphatase ≤ 2.5 times ULN
Total bilirubin ≤ 1.5 times ULN
Creatinine clearance > 50 mL/min
Creatinine ≤ 1.5 times ULN
Able to swallow tablets
No prior or concurrent malignancies within the past 5 years except for adequately treated cone-biopsied carcinoma in situ of the cervix or basal cell carcinoma of the skin
No clinically significant (i.e., active) cardiac disease, including any of the following:
- Congestive heart failure
- Symptomatic coronary artery disease
- Cardiac arrhythmia
No myocardial infarction within the past 12 months
No known significant impairment of intestinal resorption (e.g., chronic diarrhea, inflammatory bowel disease)
No pre-existing conditions that would preclude chemoradiotherapy or radiotherapy (i.e., fistulas, severe ulcerative colitis [particularly patients currently taking sulfasalazine], Crohn's disease, or prior adhesions)
No peripheral neuropathy ≥ grade 2 by CTCAE v3.0
No serious uncontrolled intercurrent infections or other serious uncontrolled concomitant disease
No history of uncontrolled seizures, central nervous system disorders or psychiatric disability that, in the opinion of the principal investigator, is clinically significant and would preclude giving informed consent or interfere with compliance with oral drug administration
No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
Not pregnant or nursing
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

No prior cytotoxic chemotherapy or radiation therapy for rectal cancer
No prior radiation therapy to the pelvis
No prior or concurrent investigational drug, agent, or procedure
More than 4 weeks since prior participation in the active or follow-up period of another investigational protocol
No known allergy or any other adverse reaction to any of the study drugs or to any related compound
No known dihydropyrimidine dehydrogenase deficiency
No organ allograft requiring immunosuppressive therapy
No concurrent sorivudine or chemically related analogues (e.g., brivudine)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00766155

Locations

Germany
Universitaetsklinikum Halle	Recruiting
Halle, Germany, D-06097
Contact: Contact Person 49 345 557-2849

Sponsors and Collaborators

European Organization for Research and Treatment of Cancer

Investigators

Principal Investigator:

Hans-Joachim Schmoll, MD, PhD

Martin-Luther-Universität Halle-Wittenberg

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000614916, EORTC-40054, EU-20880, PETACC-6, EORTC-22062, ROCHE-EORTC-40054
Study First Received:	October 2, 2008
Last Updated:	October 2, 2008
ClinicalTrials.gov Identifier:	NCT00766155
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage II rectal cancer
stage III rectal cancer
adenocarcinoma of the rectum

Study placed in the following topic categories:

Capecitabine
Digestive System Neoplasms
Rectal Neoplasms
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Intestinal Neoplasms

Rectal neoplasm
Oxaliplatin
Digestive System Diseases
Gastrointestinal Neoplasms
Adenocarcinoma
Rectal cancer
Colorectal Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Neoplasms
Antimetabolites, Antineoplastic
Neoplasms by Site

Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009