Selumetinib and Cixutumumab in Treating Patients With Advanced Solid Malignancies

NCT01061749 | Completed Phase 1

• 7 other identifiers: NCI-2012-02912NA_00028512J09618269P30CA006973U01CA070095UM1CA186691
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Adult Solid Neoplasm

Outcome Measures

Primary Outcomes (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.

  Up to 4 weeks

Secondary Outcomes (2)

• Pharmacokinetics of the combination of selumetinib and cixutumumab

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

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

  Up to 4 weeks after completion of study treatment

Study Arms (1)

Treatment (selumetinib, cixutumumab)

EXPERIMENTAL

Patients 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.

Biological: Cixutumumab; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Selumetinib

Interventions

Cixutumumab BIOLOGICAL

Given IV

Also known as: Anti-IGF-1R Recombinant Monoclonal Antibody IMC-A12, IMC-A12

Treatment (selumetinib, cixutumumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (selumetinib, cixutumumab)

Pharmacological Study OTHER

Correlative studies

Treatment (selumetinib, cixutumumab)

Selumetinib DRUG

Given PO

Also known as: ARRY-142886, AZD6244, MEK Inhibitor AZD6244

Treatment (selumetinib, cixutumumab)

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Interventions

cixutumumab; AZD 6244

Study Officials

• Nilofer Azad

  Johns Hopkins University/Sidney Kimmel Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 2, 2010
• First Posted: February 3, 2010
• Study Start: November 1, 2009
• Primary Completion: April 1, 2013
• Study Completion: September 1, 2014
• Last Updated: January 25, 2016

Record last verified: 2014-12

Locations

US (1)