Cediranib Maleate and Selumetinib Sulfate in Treating Patients With Solid Malignancies

NCT ID: NCT01364051

Last Updated: 2025-09-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-25
• Study Completion Date: 2026-03-19

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.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximally tolerated dose of cediranib maleate (AZD2171 [cediranib]) in combination with selumetinib sulfate (AZD6244 hydrogen sulfate).

II. To describe the toxicity profile associated with AZD2171 (cediranib) in combination with AZD6244 hydrogen sulfate.

III. To describe the tumor responses and identify any activity of this AZD2171 (cediranib) in combination with AZD6244 hydrogen sulfate.

IV. To explore, through correlative studies, the effect of AZD2171 (cediranib) with or without AZD6244 hydrogen sulfate on serum markers of apoptosis.

V. To assess the pharmacokinetic interaction of AZD2171 (cediranib) in combination with AZD6244 hydrogen sulfate.

VI. To study the association of clinical (toxicity and/or tumor response or activity) with the pharmacologic (pharmacokinetic/pharmacodynamic) parameters, and/or biologic (correlative laboratory study) results.

OUTLINE: This is a dose-escalation study followed by a dose-expansion cohort study.

Patients receive cediranib maleate orally (PO) once daily (QD) and selumetinib sulfate PO QD or twice daily (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.

After completion of study therapy, patients are followed up at 3 months.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (cediranib maleate, selumetinib)

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.

Group Type: EXPERIMENTAL

Cediranib

Intervention Type: DRUG

Given PO

Cediranib Maleate

Intervention Type: DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Pharmacological Study

Intervention Type: OTHER

Correlative studies

Selumetinib

Intervention Type: DRUG

Given PO

Selumetinib Sulfate

Intervention Type: DRUG

Given PO

Interventions

Cediranib

Given PO

Intervention Type: DRUG

Cediranib Maleate

Given PO

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Pharmacological Study

Correlative studies

Intervention Type: OTHER

Selumetinib

Given PO

Intervention Type: DRUG

Selumetinib Sulfate

Given PO

Intervention Type: DRUG

Other Intervention Names

AZ-D2171; AZD 2171; AZD2171; AZD2171; AZD2171 Maleate; Recentin; ARRY-142886; AZD 6244; AZD-6244; AZD6244; MEK Inhibitor AZD6244; AZD-6244 Hydrogen Sulfate; AZD6244 Hydrogen Sulfate; AZD6244 Hydrogen Sulphate; Koselugo; Selumetinib Sulphate

Eligibility Criteria

Inclusion Criteria

• 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
• Expansion phase only: willing to provide blood samples and archived tumor tissue for correlative research purposes

Exclusion Criteria

• 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)
• Patients who require concomitant agents that prolong corrected QT interval (QTc)
• Known brain or central nervous system (CNS) metastases without definitive therapy; patients who have received definitive therapy for CNS lesions may be considered if there is no evidence of progression on computed tomography (CT) or magnetic resonance imaging (MRI) imaging obtained 3 months apart
• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:

• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception
• Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation)
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Immunocompromised patients (other than that related to the use of corticosteroids) with the exception of patients known to be human immunodeficiency virus [HIV] positive and have a cluster of differentiation [CD]4 count > 400 and do not require antiretroviral therapy
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
• Other active malignancy =< 3 years prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history or prior malignancy, they must not be receiving other specific treatment (i.e. hormonal therapy) for their cancer
• Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart unless urinary protein < 1.5g in a 24 hour (hr) period or urine protein/creatinine ratio < 1.5
• History of exposure to AZD2171 (cediranib), AZD6244 hydrogen sulfate, or mitogen-activated protein kinase kinase (MEK), retrovirus-associated deoxyribonucleic acid (DNA) sequence (Ras) or v-RAF-1 murine leukemia viral oncogene homolog (Raf) inhibitors (sorafenib); Note: prior therapy with bevacizumab, sunitinib, pazopanib or aflibercept (vascular endothelial growth factor [VEGF] Trap) are allowed
• Surgery within two weeks prior to registration
• Significant hemorrhage (> 30 mL bleeding/episode in previous 3 months) or hemoptysis (> 5 mL fresh blood in previous 4 weeks)
• Mean QTc interval with Bazetts correction > 480 msec (Common Toxicity Criteria [CTC] grade 1) in screening electrocardiogram (ECG) or history of familial long QT syndrome
• Patients who are unable to swallow tablets and capsules

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brian A Costello

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic in Florida

Jacksonville, Florida, United States

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 38270822 (View on PubMed)

Other Identifiers

NCI-2012-02906

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000700596

Identifier Type: -

Identifier Source: secondary_id

MC1012

Identifier Type: -

Identifier Source: secondary_id

NCI-2011-01083

Identifier Type: -

Identifier Source: secondary_id

8810

Identifier Type: OTHER

Identifier Source: secondary_id

8810

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA015083

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA069912

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UM1CA186686

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-02906

Identifier Type: -

Identifier Source: org_study_id

NCT02876068

Identifier Type: -

Identifier Source: nct_alias