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

NCT00869570 | Completed Phase 1

• 4 other identifiers: SAKK 41/08SWS-SAKK-41-082008-006312-38CDR0000634955
• Study Type: interventional
• Target: 54
• Locations: 2 countries
• Sites: 18

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.

Conditions

Colorectal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• R0 and R1 resection

  after trial treatment (approx. 12 weeks)

• Postoperative complications

  within 8 weeks after surgery

• Time to distant failure

  during 3 years follow-up.

• Disease-free survival

  during 3 years follow-up.

• Adverse events as assessed by NCI CTCAE v3.0

  during trial treatment.

Study Arms (1)

Arm A: Sorafenib & Capecitabine & RT

EXPERIMENTAL

Sorafenib: day 1 to 33 (5 weeks, including Saturday and Sunday) every 24 hours, immediately or within two hours after RT according to the dose escalation table during phase I, and the recommended dose during phase IIa. The intake stops at the last day of RT. On nonradiotherapy days (e.g. Saturday, Sunday), the tablets have to be taken at the same time as during the week. * Capecitabine: day 1 to 33 (5 weeks, including Saturday and Sunday) according to dose escalation table during phase I, and at the recommended dose during phase IIa. The intake stops in the evening of the last day of RT. * External beam RT: Monday through Friday for 5 weeks starting on day 1 (daily fraction 1.8 Gy, final dose 45 Gy) each day at the same time (e.g. 11:00 a.m. daily). * Surgery: 6 weeks (± 1 week) after radiochemotherapy (RCT) has been completed

Drug: capecitabine; Drug: sorafenib tosylate; Radiation: radiation therapy

Interventions

capecitabine DRUG

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

Also known as: XELODA

Arm A: Sorafenib & Capecitabine & RT

sorafenib tosylate DRUG

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

Also known as: BAY 43-9006

Arm A: Sorafenib & Capecitabine & RT

radiation therapy RADIATION

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

Arm A: Sorafenib & Capecitabine & RT

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (18)

Szent Laszlo Korhaz

Budapest, 1097, Hungary

Location

Saint Claraspital AG

Basel, CH-4016, Switzerland

Location

Universitaetsspital-Basel

Basel, CH-4031, Switzerland

Location

Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli

Bellinzona, 6500, Switzerland

Location

Inselspital, Bern

Bern, CH-3010, Switzerland

Location

Spitalzentrum Biel

Biel, CH-2501, Switzerland

Location

Kantonsspital Bruderholz

Bruderholz, CH-4101, Switzerland

Location

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

Location

Hopital Cantonal Universitaire de Geneva HUG

Geneva, CH-1211, Switzerland

Location

Kantonsspital Luzern

Lucerne, 6000, Switzerland

Location

OnkoZentrum Luzern at Klinik St. Anna

Lucerne, 6006, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

SpitalSTS AG Simmental-Thun-Saanenland

Thun, 3600, Switzerland

Location

Kantonsspital Winterthur

Winterthur, CH-8400, Switzerland

Location

Onkozentrum - Klinik im Park

Zurich, 8002, Switzerland

Location

Stadtspital Triemli

Zurich, 8063, Switzerland

Location

Onkozentrum Hirslanden

Zurich, CH-8008, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, CH-8091, Switzerland

Location

Related Publications (1)

• von Moos R, Koeberle D, Schacher S, Hayoz S, Winterhalder RC, Roth A, Bodoky G, Samaras P, Berger MD, Rauch D, Saletti P, Plasswilm L, Zwahlen D, Meier UR, Yan P, Izzo P, Klingbiel D, Bartschi D, Zaugg K; Swiss Group for Clinical Cancer Research (SAKK). Neoadjuvant radiotherapy combined with capecitabine and sorafenib in patients with advanced KRAS-mutated rectal cancer: A phase I/II trial (SAKK 41/08). Eur J Cancer. 2018 Jan;89:82-89. doi: 10.1016/j.ejca.2017.11.005. Epub 2017 Dec 11.

  PMID: 29241084 RESULT

MeSH Terms

Conditions

Colorectal Neoplasms; Rectal Neoplasms

Interventions

Capecitabine; Sorafenib; Radiotherapy

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Therapeutics

Study Officials

• Roger von Moos, MD

  Kantonsspital Graubuenden

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2009
• First Posted: March 26, 2009
• Study Start: March 1, 2009
• Primary Completion: May 1, 2013
• Study Completion: September 1, 2016
• Last Updated: May 15, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1); CH (17)