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External-Beam Radiation Therapy, Capecitabine, and Sorafenib in Treating Patients With Locally Advanced Rectal Cancer

Neoadjuvant Radiotherapy Combined With Capecitabine and Sorafenib in Patients With Advanced, K-ras Mutated Rectal Cancer. A Multicenter Phase I/IIa Trial.

Status
Completed
Phases
Phase 1Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00869570
Enrollment
54
Registered
2009-03-26
Start date
2009-03-31
Completion date
2016-09-30
Last updated
2019-05-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Colorectal Cancer

Keywords

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

Brief summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving radiation therapy together with capecitabine and sorafenib 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 and best dose of capecitabine when given together with sorafenib and external-beam radiation therapy and to see how well it works in treating patients with locally advanced rectal cancer.

Detailed description

OBJECTIVES: * Determine the recommended dose of neoadjuvant capecitabine when given together with sorafenib tosylate and external-beam radiotherapy in patients with K-ras mutated, locally advanced rectal cancer. (Phase I) * Assess the efficacy and safety of this regimen in these patients. (Phase II) OUTLINE: This is a multicenter, phase I, dose-escalation study of capecitabine followed by a phase II study. Patients receive oral capecitabine twice daily and oral sorafenib tosylate once daily on days 1-33. Patients also undergo external-beam radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, and 29-33. Approximately 6 weeks after completion of neoadjuvant therapy, patients undergo surgery. After completion of study therapy, patients are followed at 8 weeks and then periodically for up to 3 years.

Interventions

DRUGcapecitabine

Phase II: 2 x 825 mg/m2 per day (during 5 weeks)

DRUGsorafenib tosylate

Phase II: 1 x 400 mg per day (during 5 weeks)

RADIATIONradiation therapy

Phase II: 1.8 Gy per day in 25 fractions (during 5 weeks)

Sponsors

Swiss Cancer Institute
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No

Inclusion criteria

DISEASE CHARACTERISTICS: * Histologically confirmed locally advanced adenocarcinoma of the rectum (with or without nodal involvement) requiring surgery * Stage mrT3-4, and/or mrN1-2, M0 disease * Tumor with K-ras gene mutation as assessed locally * No distant metastases PATIENT CHARACTERISTICS: * WHO performance status 0-1 * Neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 10.0 g/dL * Creatinine clearance ≥ 50mL/min * AST ≤ 2.5 times upper limit of normal (ULN) * Total bilirubin ≤ 1.5 times ULN * PT/INR or PTT ≤ 1.5 times ULN * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier contraception during and for 12 months after completion of study therapy * Is compliant and geographic proximity allows for proper staging and follow-up * No other malignancy within the past 5 years except adequately treated cervical carcinoma in situ or localized nonmelanoma skin cancer * No psychiatric disorder that would preclude understanding study-related information, giving informed consent, or complying with oral drug intake * No clinically significant (i.e., active) cardiac disease (e.g., congestive heart failure, symptomatic coronary artery disease, or cardiac arrhythmia \[even if controlled with medication\]) or myocardial infarction within the past 12 months * No uncontrolled hypertension * No evidence or history of bleeding diathesis * No lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome * No serious or underlying condition (e.g., active autoimmune disease, uncontrolled diabetes, or uncontrolled infection) that, in the judgement of the investigator, could preclude the ability of the patient to participate in the study * No known hypersensitivity to study drugs or to any other component of the study drugs PRIOR CONCURRENT THERAPY: * No prior treatment for rectal cancer * No prior organ allografts * More than 4 weeks since prior major surgery other than colostomy * More than 30 days since prior treatment in a clinical trial * No other concurrent experimental drugs or anticancer therapy * No concurrent brivudine, lamivudine, ribavirin, or any other nucleoside analogue * No concurrent drugs contraindicated for use with the study drugs * No other concurrent radiotherapy * No concurrent anticoagulation therapy other than low molecular weight heparin

Design outcomes

Primary

MeasureTime frame
Dose-limiting toxicity of the treatment combination (Phase I)during trial treatment (12 weeks)
Pathological near complete or complete tumor response (Dworak grade 3 and 4) (Phase II)after trial treatment (approx. 12 weeks).

Secondary

MeasureTime frame
Time to distant failureduring 3 years follow-up.
R0 and R1 resectionafter trial treatment (approx. 12 weeks)
Adverse events as assessed by NCI CTCAE v3.0during trial treatment.
Disease-free survivalduring 3 years follow-up.
Postoperative complicationswithin 8 weeks after surgery

Countries

Hungary, Switzerland

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Mar 8, 2026