Cediranib Maleate and Selumetinib Sulfate in Treating Patients With Solid Malignancies

NCT01364051 | Active Not Recruiting Phase 1

• 8 other identifiers: NCI-2012-02906CDR0000700596MC1012NCI-2011-010838810P30CA015083U01CA069912UM1CA186686
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial studies the side effects and best dose of cediranib maleate and selumetinib sulfate in treating patients with solid malignancies. Cediranib maleate and selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Cediranib maleate may also stop the growth of tumor cells by blocking blood flow to the tumor.

Conditions

Metastatic Melanoma; Refractory Malignant Solid Neoplasm; Unresectable Malignant Solid Neoplasm; Stage IV Cutaneous Melanoma AJCC v6 and v7

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  MTD will be defined as the dose level below the lowest dose that induces dose limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients). Graded per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).

  28 days

Secondary Outcomes (5)

• Incidence of adverse events, classified as either possibly, probably, or definitely related to study treatment

  Up to 3 months

• Incidence of hematologic toxicities

  Up to 3 months

• Incidence of non-hematologic toxicities

  Up to 3 months

• Overall toxicity incidence

  Up to 3 months

• Best response

  From the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started), assessed up to 3 months

Other Outcomes (3)

• Changes of the serum levels of M30 (dose expansion phase)

  Baseline up to day 22 of course 1

• Changes of the serum levels of caspase 3 (dose expansion phase)

  Baseline up to day 22 of course 1

• Changes of the serum levels of cytochrome c (dose expansion phase)

  Baseline up to day 22 of course 1

Study Arms (1)

Treatment (cediranib maleate, selumetinib)

EXPERIMENTAL

Patients receive cediranib maleate PO QD and selumetinib sulfate PO QD or BID on days 1-28 (days 8-28 of cycle 1). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cycles may be extended to 12 weeks after 1 year of study treatment.

Drug: Cediranib; Drug: Cediranib Maleate; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Selumetinib; Drug: Selumetinib Sulfate

Interventions

Cediranib DRUG

Given PO

Also known as: AZ-D2171, AZD 2171, AZD2171

Treatment (cediranib maleate, selumetinib)

Pharmacological Study OTHER

Correlative studies

Treatment (cediranib maleate, selumetinib)

Cediranib Maleate DRUG

Given PO

Also known as: AZD2171, AZD2171 Maleate, Recentin

Treatment (cediranib maleate, selumetinib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (cediranib maleate, selumetinib)

Selumetinib DRUG

Given PO

Also known as: ARRY-142886, AZD 6244, AZD-6244, AZD6244, MEK Inhibitor AZD6244

Treatment (cediranib maleate, selumetinib)

Selumetinib Sulfate DRUG

Given PO

Also known as: AZD-6244 Hydrogen Sulfate, AZD6244 Hydrogen Sulfate, AZD6244 Hydrogen Sulphate, Koselugo, Selumetinib Sulphate

Treatment (cediranib maleate, selumetinib)

Eligibility Criteria

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

You may qualify if:

• Histologic proof of cancer that is now considered clinically unresectable and for whom there is no standard therapy; NOTE: for the maximum tolerated dose (MTD) expansion cohort only: metastatic melanoma histology is required
• Measurable and non-measurable disease are eligible
• Ability to provide informed consent
• Absolute neutrophil count (ANC) \>= 1500/uL (obtained =\< 21 days prior to registration)
• Platelets (PLT) \>= 100,000/uL (obtained =\< 21 days prior to registration)
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (obtained =\< 21 days prior to registration)
• Aspartate aminotransferase (AST) =\< 2.5 x ULN or =\< 5 x ULN in presence of liver metastases (obtained =\< 21 days prior to registration)
• Creatinine =\< 1.5 x ULN (obtained =\< 21 days prior to registration)
• Hemoglobin (HgB) \>= 9.0 gm/dL (obtained =\< 21 days prior to registration)
• Alkaline phosphatase =\< 2.5 x ULN (obtained =\< 21 days prior to registration)
• Creatinine clearance \> 50 ml/min, by either Cockcroft-Gault formula or 24-hour urine collection analysis (obtained =\< 21 days prior to registration)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1
• Willing to return to Mayo for follow up
• Life expectancy \>= 12 weeks
• Women of childbearing potential only: negative serum pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only

You may not qualify if:

• Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Any of the following prior therapies:
• Chemotherapy =\< 28 days prior to registration
• Mitomycin C/nitrosoureas =\< 42 days prior to registration
• Immunotherapy =\< 28 days prior to registration
• Biologic therapy =\< 28 days prior to registration
• Radiation therapy =\< 28 days prior to registration
• Radiation to \> 25% of bone marrow
• Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
• Cardiac conditions as follows:
• Uncontrolled hypertension (blood pressure \[BP\] \>= 150/95 despite optimal therapy)
• Heart failure New York Heart Association (NYHA) class II or above or left ventricular ejection fraction \< 50%
• Atrial fibrillation with heart rate \> 100 beats per minute (bpm)
• Unstable ischemic heart disease (myocardial infarction \[MI\] within 6 months prior to starting treatment, or angina requiring use of nitrates more than once weekly)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Emiloju OE, Yin J, Koubek E, Reid JM, Borad MJ, Lou Y, Seetharam M, Edelman MJ, Sausville EA, Jiang Y, Kaseb AO, Posey JA, Davis SL, Gores GJ, Roberts LR, Takebe N, Schwartz GK, Hendrickson AEW, Kaufmann SH, Adjei AA, Hubbard JM, Costello BA. Phase 1 trial of navitoclax and sorafenib in patients with relapsed or refractory solid tumors with hepatocellular carcinoma expansion cohort. Invest New Drugs. 2024 Feb;42(1):127-135. doi: 10.1007/s10637-024-01420-8. Epub 2024 Jan 25.

  PMID: 38270822 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

cediranib; AZD 6244

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Brian A Costello

  Mayo Clinic

  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: May 26, 2011
• First Posted: June 2, 2011
• Study Start: May 25, 2011
• Primary Completion: June 6, 2019
• Study Completion (Estimated): March 31, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-03

Locations

US (2)