Pemetrexed Disodium and Sorafenib Tosylate in Treating Patients With Advanced Solid Tumors

NCT01450384 | Completed Phase 1 DMC

• 3 other identifiers: MCC-13874NCI-2011-03035P30CA016059
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of giving pemetrexed disodium and sorafenib tosylate together in treating patients with advanced solid tumors. Pemetrexed disodium and sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib tosylate may also stop the growth of solid tumors by blocking blood flow to the tumor. Giving pemetrexed disodium together with sorafenib tosylate may kill more tumor cells.

Conditions

Unspecified Adult Solid Tumor

Keywords

protocol specific

Outcome Measures

Primary Outcomes (1)

• Recommended phase 2 doses for the combination of pemetrexed disodium with sorafenib tosylate

  Maximum doses of pemetrexed and sorafenib, which, when administered in combination are determined to be tolerable and will be tested in a Phase 2 trial for efficacy.

  At least 4 weeks

Secondary Outcomes (4)

• Number of subjects in whom study treatment produces antitumor effects of the combination

  Up to 4 years

• Number of biopsy specimens that successfully stain for Beclin1

  Baseline up to 4 weeks

• Number of biopsy specimens that can be analyzed for PDGFRb expression

  Baseline up to 4 weeks

• Analysis of pTEN expression in biopsy specimens

  Baseline up to 4 weeks

Study Arms (1)

Treatment (enzyme inhibitor therapy, antiangiogenesis)

EXPERIMENTAL

Patients receive pemetrexed disodium IV on day 1 every 2 weeks and sorafenib tosylate PO BID for 4 weeks on days 1-5. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Drug: sorafenib tosylate; Drug: pemetrexed disodium; Other: laboratory biomarker analysis; Procedure: biopsy

Interventions

sorafenib tosylate DRUG

Given PO

Also known as: BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar, SFN

Treatment (enzyme inhibitor therapy, antiangiogenesis)

pemetrexed disodium DRUG

Given IV

Also known as: ALIMTA, LY231514, MTA

Treatment (enzyme inhibitor therapy, antiangiogenesis)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (enzyme inhibitor therapy, antiangiogenesis)

biopsy PROCEDURE

Optional correlative studies

Also known as: biopsies

Treatment (enzyme inhibitor therapy, antiangiogenesis)

Eligibility Criteria

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

You may qualify if:

• Advanced solid tumor malignancy for which there is no potentially curative treatment; there is no limit to the number of prior lines of therapy
• Performance status Eastern Cooperative Oncology Group (ECOG) equal or less than 1
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =\< 3 x upper institutional limit (ULN)
• Total bilirubin =\< 1.5 ULN
• Creatinine clearance (CrCl) \>= 45 mL/min as measured by the standard Cockcroft-Gault equation
• International normalized ratio (INR) =\< 1.5 (if not due to anticoagulants)
• White blood cell count (WBC) \>= 3,000 cells/mm3
• Absolute neutrophil count (ANC) \>= 1,500 cells/mm3
• Platelets \>= 100,000 cells/mm3
• Hemoglobin (Hgb) \>= 8.5 g/dL
• Prior toxicities are allowed as long as they are stable and would not interfere with study drug toxicity assessment
• Measurable or evaluable disease by Response Evaluation Criteria In Solid Tumors (RECIST) (v 1.1)
• Ability to understand and the willingness to sign a written informed consent document; a signed informed consent must be obtained prior to any study specific procedures
• Women of childbearing potential must have a negative pregnancy test performed within 7 days prior to the start of treatment; women of childbearing potential and men must agree to use a medically accepted form of birth control for the duration of study participation; men must agree to use a medically accepted form of birth control for 2 months following completion of study treatment

You may not qualify if:

• Any investigational agent within 4 weeks of first dose of study treatment
• Unwillingness or inability to take folic acid, vitamin B12, or dexamethasone
• Known or presumed intolerance of pemetrexed or sorafenib; unable to swallow medication; suspected malabsorption
• Active illicit substance or alcohol abuse
• Contraindication to antiangiogenic agents, including:
• Pulmonary hemorrhage/bleeding event \>= Grade 2 within 4 weeks or less prior to the first dose of study drug
• Any other hemorrhage/bleeding event \>= Grade 3 within 4 weeks or less prior to the first dose of study drug
• Serious non-healing wound, ulcer, or bone fracture
• Thrombolic or embolic events such as a myocardial infarction, cerebrovascular accident including transient ischemic attacks within the past 6 months
• Major cardiac dysfunction, such as uncontrolled angina, congestive heart failure with New York Heart Association (NYHA) class III or higher, ventricular arrhythmias requiring anti-arrhythmic therapy
• Systolic blood pressure \> 160 mmHg or diastolic pressure \> 100 mmHg despite optimal medical management
• Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents for a 5 day period
• Serious uncontrolled infection \> Common Terminology Criteria for Adverse Events (CTCAE) (v 4) grade 2
• Peripheral motor or sensory neuropathy\>CTCAE (v4) grade 2
• Uncontrolled metastatic brain disease

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Interventions

Sorafenib; Pemetrexed; Biopsy

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Andrew Poklepovic

  Massey Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 30, 2011
• First Posted: October 12, 2011
• Study Start: October 1, 2011
• Primary Completion: January 1, 2015
• Study Completion: September 1, 2015
• Last Updated: February 23, 2016

Record last verified: 2016-02

Locations

US (1)