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Recurrent Colon CancerPhase 1NCT00134069

Sorafenib, Cetuximab, and Irinotecan in Treating Patients With Advanced or Metastatic Colorectal Cancer

A Phase 1 study testing sorafenib tosylate, cetuximab and irinotecan hydrochloride in people with Recurrent Colon Cancer and Recurrent Rectal Cancer, run by National Cancer Institute (NCI) at 2 sites in United States.

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

This phase I/II trial is studying the side effects and best dose of sorafenib when given together with cetuximab and irinotecan and to see how well they work in treating patients with advanced or metastatic colorectal cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
sorafenib tosylate, cetuximab and irinotecan hydrochloride
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
2 sitesUnited States
Study dates
Jun 2005to Dec 2011
Phase
Phase 1
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically confirmed colorectal cancer (advanced or metastatic disease not amenable to potential curative resection)
  • Archival tumor (blocks and/or slides) must be available for patients who decline tumor biopsies
  • Tumor must be amenable to sequential biopsies for patients willing to undergo tumor biopsy
  • Must have evidence of disease progression after first-line chemotherapy for advanced disease
  • Previously irradiated lesions are not considered measurable disease
  • Measurable disease, defined as >= 1 unidimensionally measurable target lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan
Show all 62Show fewer
  • No known brain metastases
  • Eastern Cooperative Oncology Group (ECOG) 0-2 OR Karnofsky 60-100%
  • Life expectancy of more than 12 weeks
  • white blood cell count (WBC) >= 3,000/mm^3
  • Bilirubin normal
  • Creatinine normal OR creatinine clearance >= 60 mL/min
  • No hypertension
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • Not pregnant or nursing
  • Able to swallow oral medication
  • Willing to undergo 2 sequential tumor and skin biopsies
  • No ongoing or active infection
  • No history of allergic reaction attributed to compounds of similar chemical or biologic composition to study drugs
  • No psychiatric illness or social situation that would preclude study compliance
  • No other uncontrolled illness
  • No prior cetuximab
  • No concurrent prophylactic filgrastim (G-CSF), sargramostim (GM-CSF) or epoetin alfa
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
  • No other concurrent chemotherapy
  • More than 4 weeks since prior radiotherapy and recovered
  • No prior sorafenib
  • No other prior therapy targeted against MAPK
  • More than 14 days since prior and no concurrent administration of the following cytochrome P450 3A4 (CYP3A4) inducers:
  • Rifampin
  • Rifabutin
  • Hypericum perforatum (St. John's wort)
  • Phenytoin
  • Carbamazepine
  • Phenobarbital
  • More than 7 days since prior and no concurrent administration of the following CYP3A4 inhibitors:
  • Amiodarone
  • Clarithromycin
  • Diltiazem
  • Erythromycin
  • Grapefruit juice
  • Indinavir
  • Saquinavir
  • Lopinavir in combination with ritonavir
  • Fosamprenavir
  • Ritonavir
  • Atazanavir
  • Nelfinavir
  • Itraconazole
  • Ketoconazole
  • Nefazodone
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational agents
  • No other concurrent anticancer therapy
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Absolute neutrophil count >=1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • No evidence of bleeding diathesis
  • Aspartate aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 times upper limit of normal

Who cannot join

None listed.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of Colorado at Denver Health Sciences Center

    Aurora, Colorado, 80045

  • Johns Hopkins University

    Baltimore, Maryland, 21287-8936

Other trials in United States

About this study

Official title: Phase I/II Clinical, Pharmacological, and Biological Study of BAY 43-9006 in Combination With Cetuximab and Irinotecan in Patients With Advanced Colorectal Cancer

This phase I/II trial is studying the side effects and best dose of sorafenib when given together with cetuximab and irinotecan and to see how well they work in treating patients with advanced or metastatic colorectal cancer. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. Sorafenib and cetuximab may also stop tumor growth by blocking blood flow to the tumor. Drugs used in chemotherapy, such as irinotecan, work in different ways to kill tumor cells, either by killing the cells or by stopping them from dividing. Giving sorafenib together with cetuximab and irinotecan may kill more tumor cells

Read the detailed description

OBJECTIVES:

  1. Determine the toxicity spectrum and dose-limiting toxic effects of sorafenib when combined with cetuximab and irinotecan in patients with advanced or metastatic colorectal cancer.

II. Determine the recommended phase II dose of sorafenib when combined with cetuximab and irinotecan in these patients.

III. Correlate the clinical activity of this regimen, in terms of radiologic and positron emission tomography (PET) response, with baseline extracellular signal-regulated kinase (ERK) expression as well as Kirsten rat sarcoma (KRAS), BRAF, and other genetic properties of tumors in these patients.

IV. Determine the pharmacokinetics of this regimen in these patients. V. Correlate the pharmacodynamic effects of this regimen with baseline ERK expression as well as KRAS, BRAF, and other genetic properties of tumors in these patients.

VI. Correlate the pharmacodynamic effects of this regimen on mitogen-activated protein kinase (MAPK) status in peripheral blood mononuclear cells and on normal skin and oral mucosa with clinical parameters in these patients.

OUTLINE: This is a phase I dose-escalation study of sorafenib followed by a multicenter phase II study.

PHASE I:

COURSE 1 (56 days): Patients receive oral sorafenib once or twice daily on days 1-56, cetuximab IV over 1-2 hours on days 1, 8,15, 22, 29, 36, 43, and 50, and irinotecan IV over 90 minutes on days 15, 22, 29, and 36.

COURSE 2 AND ALL SUBSEQUENT COURSES (42 days): Patients receive oral sorafenib once or twice daily on days 1-42, cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36, and irinotecan IV over 90 minutes on days 1, 8, 15, and 22. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of sorafenib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

PHASE II: Patients receive sorafenib at the MTD determined in phase I, cetuximab, and irinotecan as in phase I.

After completion of study treatment, patients are followed at 30 days.

*NOTE: This trial was intended to be Phase I/II, but the trial never continued to the Phase II portion.

Being tested
sorafenib tosylate, cetuximab, irinotecan hydrochloride
Medical subject headings
Colonic Neoplasms, Rectal Neoplasms

What participants receive

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

  • sorafenib tosylateDrug

    Also called BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar

    Given orally

  • cetuximabDrug

    Also called C225, C225 monoclonal antibody, IMC-C225, MOAB C225

    Given IV

  • irinotecan hydrochlorideDrug

    Also called Campto, Camptosar, CPT-11, irinotecan

    Given IV

Study groups in NCT00134069
Study groupRoleWhat they receive
Treatment (sorafenib, irinotecan, cetuximab)ExperimentalPatients will receive sorafenib by mouth once or twice a day and a 1- to 2-hour infusion of cetuximab once a week for 8 weeks. They will also receive a 1½-hour infusion of irinotecan once a week in weeks 3-6. Patients will then receive sorafenib by mouth once or twice a day and a 1- to 2-hour infusion of cetuximab once a week for 6 weeks. They will also receive a 1½-hour infusion of irinotecan once a week in weeks 1-4. Treatment may repeat every 6 weeks for as long as benefit is shown.
Receives: Drug: sorafenib tosylate; Drug: cetuximab; Drug: irinotecan hydrochloride

What is being measured

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

  1. Toxicity spectrum and dose-limiting toxicities of sorafenib in combination with cetuximab and irinotecan as assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v 3.0

    Measured: Up to 30 days

  2. Recommended dose for phase II evaluation of the combination of sorafenib, cetuximab and irinotecan

    Measured: 56 days

  3. Clinical activity of the combination of sorafenib, cetuximab and irinotecan in terms of radiological response

    Measured: Up to 30 days

  4. Pharmacokinetics of sorafenib, cetuximab, and irinotecan when given in combination or when given in combination with cetuximab alone and with cetuximab and irinotecan

    Measured: Up to 30 days

  5. Pharmacodynamics of the combination of irinotecan when given in combination with sorafenib and cetuximab in tumor tissues

    Measured: Up to 30 days

Timeline

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

  1. First posted24 Aug 2005 (estimated)
  2. Study startJun 2005
  3. Primary completionSep 2010
  4. Study completionDec 2011

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00134069
Sponsor's protocol ID
NCI-2009-00110
Other IDs
07-0571, R21CA117125, U01CA070095
Status last verified
Apr 2014
First submitted
22 Aug 2005
Last updated
16 Apr 2014
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing sorafenib tosylate, cetuximab and irinotecan hydrochloride in people with Recurrent Colon Cancer and Recurrent Rectal Cancer, run by National Cancer Institute (NCI) at 2 sites in United States.

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

Who may be eligible to take part?

The sponsor lists 62 inclusion and 0 exclusion criteria. 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 16 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. 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 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.

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?

Toxicity spectrum and dose-limiting toxicities of sorafenib in combination with cetuximab and irinotecan as assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v 3.0 (time frame: Up to 30 days). The study lists 5 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 NCT00134069.

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 16 Apr 2014.

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