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Recurrent Colon CancerPhase 1NCT01217450

Selumetinib and Cetuximab in Treating Patients With Refractory Solid Tumors

A Phase 1 study testing selumetinib, cetuximab and laboratory biomarker analysis in people with Recurrent Colon Cancer and Recurrent Rectal Cancer, run by National Cancer Institute (NCI) at 3 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 trial is studying the side effects and the best dose of MEK Inhibitor AZD6244 when given together with cetuximab in patients with advanced or refractory solid tumors that cannot be removed by surgery. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
selumetinib, cetuximab and laboratory biomarker analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
3 sitesUnited States
Study dates
Oct 2012to May 2014
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

  • In the dose escalation cohorts: Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective; histology can be based on either the primary tumor or metastases
  • In the MTD expansion cohort: Patients must have biopsy proven K-RAS mutant, metastatic colorectal cancer that has progressed on at least 2 prior standard therapies; K-RAS mutation status must be verified by a CLIA-certified laboratory (NOTE: colorectal patients enrolled during the dose escalation portion do not need to be K-RAS mutant in order to be eligible)
  • Patients must be at least 4 weeks since prior chemotherapy, 6 weeks if the last regimen included nitrosureas or mitomycin C; prior radiation is allowed as long as the radiation was completed 4 weeks prior to study treatment and no more than 35% of marrow irradiated
  • ECOG performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of greater than 3 months
  • Leukocytes >= 3,000/mcL
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  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal (AST and ALT =< 5.0 X institutional upper limit of normal will be permitted if liver metastases are present)
  • Creatinine =< 1.5 X institution upper limit of normal OR creatinine clearance >= 45 mL/min/1.73 m^2, as calculated by Cockroft-Gault formula, for patients with creatinine levels above institutional normal
  • Patients may have received prior cetuximab
  • The effects of AZD6244 on the developing human fetus are unknown; for this reason and because small molecule kinase inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for 16 weeks following the last dose of study treatment. Acceptable methods of birth control include implants, injectables, combined oral contraceptives, (which must all be combined with barrier methods of contraception), some IUDs, sexual abstinence, and vasectomized partner; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document
  • Patients with brain metastases that have been treated and stable for 2 months will be eligible for this study
  • Subjects undergoing anti-coagulation therapy with LMWH and warfarin are eligible; subjects receiving both warfarin and AZD6244 should have more frequent PT/INR monitoring

Who cannot join

  • Patients who have had chemotherapy, radiotherapy or hormonal therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered (=< grade 1) from adverse events due to agents administered more than 4 weeks earlier
  • Concurrent treatment with an investigational agent other than the investigational agent(s) used in this study OR treatment within 4 weeks of study entry with any investigational agent(s) or device(s)
  • Failure to recover fully (as judged by the investigator) from prior surgical procedures
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD6244 or other agents used in study
  • Patients taking high doses (more than recommended daily dose) of vitamin E will be excluded; patients can discontinue use of high dose vitamin E prior to study entry to be considered eligible
  • Any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain AZD6244 capsules
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  • Patients with malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel are excluded; subjects with ulcerative colitis, inflammatory bowel disease, or a partial or complete small bowel obstruction are also excluded
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, prior cardiomyopathy, LVEF < 50%, unstable angina pectoris, cardiac arrhythmia (i.e. atrial fibrillation), or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because AZD6244 is a small molecule kinase inhibitor with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AZD6244, breastfeeding should be discontinued if the mother is treated with AZD6244; these potential risks may also apply to other agents used in this study
  • HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD6244; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  • Patients who are serologically positive for Hepatitis B or C, or have a history of liver disease, other forms of hepatitis or cirrhosis are ineligible
  • Use of strong CYP1A2 or 3A4 inducers and/or inhibitors (for example, but not limited to, ketoconazole, rifampicin, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin (TAO), voriconazole, grapefruit or grapefruit juice, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital and St. John's Wort) is not permitted while on study or within 7 days prior to study enrollment

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • National Cancer Institute Medicine Branch

    Bethesda, Maryland, 20892

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Wisconsin Clinical Cancer Center

    Milwaukee, Wisconsin, 53226

Other trials in United States

About this study

Official title: A Phase 1 Study of AZD6244 in Combination With Cetuximab in Refractory Solid Tumors

This phase I trial is studying the side effects and the best dose of MEK Inhibitor AZD6244 when given together with cetuximab in patients with advanced or refractory solid tumors that cannot be removed by surgery. MEK inhibitor AZD6244 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. Giving MEK Inhibitor AZD6244 together with cetuximab may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the dose limiting toxicities and the maximum tolerated dose of AZD6244 in combination with cetuximab in advanced, refractory solid tumors.

II. To assess for evidence of anti-tumor activity with this combination, per tumor measurements using RECIST criteria.

SECONDARY OBJECTIVES:

  1. To evaluate the pharmacokinetics of AZD6244 and cetuximab when administered concomitantly.

II. To evaluate the safety and tolerability of the combination of AZD6244 and cetuximab in patients with K-RAS mutated metastatic colorectal cancer.

TERTIARY OBJECTIVES:

  1. To assess the inhibition of the RAF/MEK/ERK pathway in peripheral blood mononuclear cells secondary to treatment with AZD6244.

II. To evaluate the pharmacokinetics of AZD6244 in combination with cetuximab and the relation to treatment side effects.

OUTLINE: This is a dose-escalation study of MEK inhibitor AZD6244.

Patients receive oral MEK inhibitor AZD6244 once or twice daily on days 1-28 and cetuximab IV over 60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline and periodically during study for pharmacokinetic and biomarker analyses.

After completion of study treatment, patients are followed up for 1 month or every 3 months for 1 year.

Being tested
selumetinib, cetuximab, laboratory biomarker analysis, pharmacological study
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.

  • selumetinibDrug

    Also called ARRY-142886, AZD6244

    Given orally

  • cetuximabBiological

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

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

Study groups in NCT01217450
Study groupRoleWhat they receive
Treatment (selumetinib, cetuximab)ExperimentalPatients receive oral MEK inhibitor AZD6244 once or twice daily on days 1-28 and cetuximab IV over 60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: selumetinib; Biological: cetuximab; Other: laboratory biomarker analysis; Other: pharmacological study

What is being measured

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

  1. MTD of selumetinib combined with cetuximab

    Graded using the NCI Common Toxicity Criteria.

    Measured: 28 days

  2. Tumor response, as evaluated by the RECIST

    Analyzed by descriptive statistics, and summarized in tabular format. 95% confidence intervals will be computed using the method proposed by Chang.

    Measured: Up to 4 weeks after completion of study treatment

Secondary outcomes (1)

  1. Toxicities graded using the NCI Common Toxicity Criteria

    Summarized in terms of types and severities. Analyzed descriptively in tabular format. Ninety percent confidence intervals for the proportions of patients with complications (grade 3 or higher toxicities) will be constructed using the Wilson's score method.

    Measured: Up to 4 weeks after completion of study treatment

Timeline

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

  1. First posted8 Oct 2010 (estimated)
  2. Study startOct 2012
  3. Primary completionDec 2012
  4. Study completionMay 2014

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
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01217450
Sponsor's protocol ID
NCI-2012-02915
Other IDs
NCI-2012-02915, CDR0000686619, CO10901, 8627, P30CA014520, U01CA062491
Status last verified
Dec 2013
First submitted
7 Oct 2010
Last updated
29 May 2014
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing selumetinib, cetuximab and laboratory biomarker analysis in people with Recurrent Colon Cancer and Recurrent Rectal Cancer, run by National Cancer Institute (NCI) at 3 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 16 inclusion and 12 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 29 May 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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?

MTD of selumetinib combined with cetuximab (time frame: 28 days). 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 NCT01217450.

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 29 May 2014.

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