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Colorectal CancerPhase 1/2NCT00869570

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

A Phase 1/2 study testing capecitabine, sorafenib tosylate and radiation therapy in people with Colorectal Cancer, run by Swiss Cancer Institute at 18 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Colorectal Cancer
What is being tested?
capecitabine, sorafenib tosylate and radiation therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
18 sitesin 2 countries
Study dates
Mar 2009to Sep 2016
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

18 sites in 2 countries.

18 sites in 2 countries

Switzerland17 sites

  • Saint Claraspital AG

    Basel, CH-4016

  • Universitaetsspital-Basel

    Basel, CH-4031

  • Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli

    Bellinzona, 6500

  • Inselspital, Bern

    Bern, CH-3010

  • Spitalzentrum Biel

    Biel, CH-2501

  • Kantonsspital Bruderholz

    Bruderholz, CH-4101

  • Kantonsspital Graubuenden

    Chur, CH-7000

  • Hopital Cantonal Universitaire de Geneva HUG

    Geneva, CH-1211

  • Kantonsspital Luzern

    Lucerne, 6000

  • OnkoZentrum Luzern at Klinik St. Anna

    Lucerne, 6006

  • Kantonsspital - St. Gallen

    Sankt Gallen, CH-9007

  • SpitalSTS AG Simmental-Thun-Saanenland

    Thun, 3600

  • Kantonsspital Winterthur

    Winterthur, CH-8400

  • Onkozentrum - Klinik im Park

    Zurich, 8002

  • Stadtspital Triemli

    Zurich, 8063

  • Onkozentrum Hirslanden

    Zurich, CH-8008

  • UniversitaetsSpital Zuerich

    Zurich, CH-8091

Other trials in Switzerland

Hungary1 site

  • Szent Laszlo Korhaz

    Budapest, 1097

Other trials in Hungary

About this study

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

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.

Read the 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.

Being tested
capecitabine, sorafenib tosylate, radiation therapy
Keywords
adenocarcinoma of the rectum, stage II rectal cancer, stage III rectal cancer
Medical subject headings
Colorectal Neoplasms, Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • capecitabineDrug

    Also called XELODA

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

  • sorafenib tosylateDrug

    Also called BAY 43-9006

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

  • radiation therapyRadiation

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

Study groups in NCT00869570
Study groupRoleWhat they receive
Arm A: Sorafenib & Capecitabine & RTExperimentalSorafenib: 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
Receives: Drug: capecitabine; Drug: sorafenib tosylate; Radiation: radiation therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose-limiting toxicity of the treatment combination (Phase I)

    Measured: during trial treatment (12 weeks)

  2. Pathological near complete or complete tumor response (Dworak grade 3 and 4) (Phase II)

    Measured: after trial treatment (approx. 12 weeks).

Secondary outcomes (5)

  1. R0 and R1 resection

    Measured: after trial treatment (approx. 12 weeks)

  2. Postoperative complications

    Measured: within 8 weeks after surgery

  3. Time to distant failure

    Measured: during 3 years follow-up.

  4. Disease-free survival

    Measured: during 3 years follow-up.

  5. Adverse events as assessed by NCI CTCAE v3.0

    Measured: during trial treatment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Mar 2009 (estimated)
  2. Study startMar 2009
  3. Primary completionMay 2013
  4. Study completionSep 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00869570
Sponsor's protocol ID
SAKK 41/08
Other IDs
SWS-SAKK-41-08, 2008-006312-38, CDR0000634955, 2008
Status last verified
May 2019
First submitted
25 Mar 2009
Last updated
15 May 2019
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • 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.

    PubMed 29241084

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing capecitabine, sorafenib tosylate and radiation therapy in people with Colorectal Cancer, run by Swiss Cancer Institute at 18 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in Switzerland, Hungary. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting toxicity of the treatment combination (Phase I) (time frame: during trial treatment (12 weeks)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00869570, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2019.

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