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Adult Solid NeoplasmPhase 1NCT01061749

Selumetinib and Cixutumumab in Treating Patients With Advanced Solid Malignancies

A Phase 1 study testing Cixutumumab, Laboratory Biomarker Analysis and Pharmacological Study in people with Adult Solid Neoplasm, run by National Cancer Institute (NCI) at 1 site 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 clinical trial studies the safety and best dose of selumetinib and cixutumumab in treating patients with advanced solid malignancies. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Adult Solid Neoplasm
What is being tested?
Cixutumumab, Laboratory Biomarker Analysis and Pharmacological Study
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
Nov 2009to Sep 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

  • Patients must have a histologically-confirmed metastatic or locally advanced solid tumor that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist
  • There is no limit on the number of prior treatment regimens
  • Patients must be off prior chemotherapy, radiation therapy, hormonal therapy, or biological therapy for at least 4 weeks; patients who were receiving mitomycin C, nitrosoureas, or carboplatin must be 6 weeks from the last administration of chemotherapy; patients with prostate cancer may continue to receive LHRH agonist (unless orchiectomy has been performed)
  • ECOG performance status 0-1
  • Life expectancy of greater than 3 months
  • Leukocytes >= 3,000/mcL
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  • Absolute neutrophil count >= 1,200/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 9 mg/dL
  • Albumin >= 2.5 g/dL
  • Total bilirubin =< 1.5 X institutional upper limits of normal in the absence of Gilbert's syndrome
  • AST(SGOT) and ALT(SGPT) =< 2.5 X institutional upper limit of normal
  • Serum glucose =< 120 mg/dL
  • Creatinine =< 1.5 mg/dL OR creatinine clearance >= 45 mL/min for patients with creatinine levels above institutional normal.
  • Patients must have recovered from toxicity related to prior therapy to at least grade 1 (defined by CTEP Active Version of the CTCAE); chronic stable grade 2 peripheral neuropathy secondary to neurotoxicity from prior therapies may be considered on a case by case basis by the Principal Investigator
  • As the effect of AZD6244 and IMC-A12 in combination on the developing human fetus is not known, women of child-bearing potential and men must agree to use adequate contraception (abstinence; hormonal or barrier method of birth control) for the study and at least 3 months after completion
  • Female patient of childbearing potential has a negative serum pregnancy test within 7 days of study enrollment
  • Ability to understand and the willingness to sign a written informed consent document
  • Measurable disease
  • Patient must be able to swallow pills
  • Patients must have LVEF > 45% before starting therapy as measured by echocardiogram or MUGA
  • Patients should have a baseline ophthalmologic examination before starting therapy

Who cannot join

  • Patient current evidence of active and uncontrolled infection, documented Child's class B-C cirrhosis, or active pancreatitis
  • Uncontrolled hypertension (BP > 150/95 despite optimal therapy)
  • Left ventricular ejection fraction of =< 45% or NYHA Class II-IV CHF
  • Prior or current cardiomyopathy
  • Atrial fibrillation with heart rate > 100 bpm
  • Unstable ischemic heart disease (myocardial infarction within 6 months prior to starting treatment, or angina requiring use of nitrates more than once weekly)
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  • Patients receiving any medications that are inhibitors or inducers of specific CYP450 enzyme(s) are ineligible
  • History of growth hormone deficiency or excess, or patient is concurrently using growth hormone (GH), or growth hormone inhibitors
  • Patient has a known hypersensitivity to the components of study drugs, its analogs, or drugs of similar chemical or biologic composition
  • Patient has prior exposure to IGF-1R or RAF/MEK inhibitors
  • The patient has poorly controlled diabetes mellitus, defined as a Hba1c > 7%
  • Patients with active CNS metastases and/or carcinomatous meningitis are excluded; however, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for 3 months prior to entry as defined as:
  • No evidence of new or enlarging CNS metastasis
  • No new signs or symptoms consistent with CNS metastasis
  • Off steroids or on a stable dose of steroids for at least four weeks
  • Patient with a primary central nervous system tumor
  • Patient has known psychiatric or substance abuse disorders that is uncontrolled and would interfere with cooperation with the requirements of the trial
  • Patient is pregnant or breastfeeding.
  • Patient is Human Immunodeficiency virus (HIV)-positive and on highly active antiretroviral therapy (HAART), as drug interactions between those agents and these experimental agents are wholly unknown; if this combination goes forward, this regimen will need to be tested in this group of patients in the future; patients with HIV who are well compensated and do not require HAART therapy are eligible for the study
  • Patient has active hepatitis B or C on treatment
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days of day 1 of therapy
  • Use of any other concurrent investigational agents or anticancer agents including hormonal therapy, except in the case of prostate cancer patients who are being treated with LHRH agonist at the time of trial entry
  • Patients should avoid excessive sun exposure and use adequate sunscreen protection if sun exposure is anticipated
  • History of any serious intraocular or retinal pathology as determined by the reference ophthalmologist, with the exception of controlled glaucoma or cataracts; in particular, patients with a history of retinal vein occlusion (RVC) or central serous retinopathy (CSR), or predisposing factors to RVO or CSR as assessed by ophthalmic exam (e.g. evidence of new optic disc cupping, new visual field defects, intraocular pressure > 21 mmHg, uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes) must be excluded

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

Other trials in United States

About this study

Official title: A Phase I, Single-Institution Open Label, Dose-Escalation Trial With an Expansion Trial Cohort Evaluating the Safety and Tolerability of AZD6244 and IMC-A12 in Subjects With Advanced Solid Malignancies

This phase I clinical trial studies the safety and best dose of selumetinib and cixutumumab in treating patients with advanced solid malignancies. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor to grow and spread. Others find tumor cells and help kill them or carry [cancer/tumor]-killing substances to them.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the safety and toxicity of the combination of AZD6244 and IMC-A12 in advanced solid tumors that have progressed on standard therapy.

II. Finding the maximum tolerated dose (MTD)/recommended phase II dose of the combination.

SECONDARY OBJECTIVES:

  1. Explore preliminary evidence of efficacy of the combination of AZD6244 and IMC-A12 in advanced solid tumors using RECIST criteria for tumor response.

II. Define pharmacodynamic (PD) profile of the combination of IMC-A12 and AZD6244.

III. Correlate pharmacokinetics (PK) of the combination of IMC-A12 and AZD6244 to pharmacodynamic (PD) endpoints.

IV. Assess the PK/PD (phospho-S6) link with AZD6244 when administered in combination with IMC-A12.

OUTLINE: This is a dose-escalation study of selumetinib and cixutumumab.

Patients receive selumetinib orally (PO) twice daily (BID) on days 1-28 and cixutumumab intravenously (IV) on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks.

Being tested
Cixutumumab, Laboratory Biomarker Analysis, Pharmacological Study, Selumetinib

What participants receive

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

  • CixutumumabBiological

    Also called Anti-IGF-1R Recombinant Monoclonal Antibody IMC-A12, IMC-A12

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • SelumetinibDrug

    Also called ARRY-142886, AZD6244, MEK Inhibitor AZD6244

    Given PO

Study groups in NCT01061749
Study groupRoleWhat they receive
Treatment (selumetinib, cixutumumab)ExperimentalPatients receive selumetinib PO BID on days 1-28 and cixutumumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Cixutumumab; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Selumetinib

What is being measured

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

  1. Maximum tolerated dose of selumetinib in combination with cixutumumab defined as the dose produced DLT in =< 1 out of 6 patients

    The proportion of patients with serious or life threatening toxicities will be estimated along with 95% confidence intervals. Tabulated by dose combination, by toxicity type, and by the severity.

    Measured: Up to 4 weeks

Secondary outcomes (2)

  1. Pharmacokinetics of the combination of selumetinib and cixutumumab

    Peak serum level (Cmax), the trough level (Cmin), and the Area Under the serum concentration time Curve (AUC) will be summarized using descriptive statistics.

    Measured: Prior to the dose and at 0.5, 1, 1.5, 2, 4, and 8 hours

  2. The proportion of patients who experience PR, CR, or SD as defined by RECIST criteria

    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 posted3 Feb 2010 (estimated)
  2. Study startNov 2009
  3. Primary completionApr 2013
  4. Study completionSep 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
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01061749
Sponsor's protocol ID
NCI-2012-02912
Other IDs
NCI-2012-02912, NA_00028512, J0961, 8269, P30CA006973, U01CA070095, UM1CA186691
Status last verified
Dec 2014
First submitted
2 Feb 2010
Last updated
25 Jan 2016
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cixutumumab, Laboratory Biomarker Analysis and Pharmacological Study in people with Adult Solid Neoplasm, run by National Cancer Institute (NCI) at 1 site 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 22 inclusion and 24 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 25 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

Maximum tolerated dose of selumetinib in combination with cixutumumab defined as the dose produced DLT in =< 1 out of 6 patients (time frame: Up to 4 weeks). 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 NCT01061749.

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 25 Jan 2016.

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