Sorafenib Combined With Cisplatin and Etoposide or Carboplatin and Pemetrexed in Treating Patients With Metastatic Solid Tumors

NCT00573690 | Completed Phase 1 DMC

• 3 other identifiers: LCCC 0613CDR0000579819UNC-LCC-07-0971
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Sorafenib and pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as cisplatin, etoposide, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sorafenib together with cisplatin and etoposide or carboplatin and pemetrexed may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of sorafenib when given together with cisplatin and etoposide or carboplatin and pemetrexed in treating patients with metastatic solid tumors.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specific

Outcome Measures

Primary Outcomes (1)

• Recommended phase II dose and maximum tolerated dose of sorafenib tosylate when administered in combination with cisplatin and etoposide or carboplatin and pemetrexed disodium

  12 months

Secondary Outcomes (3)

• Toxicity

  12 months

• Efficacy of treatment as measured by RECIST criteria or by tumor markers

  36 months

• Pharmacokinetics of sorafenib tosylate in combination with etoposide (samples are no longer being collected and studies are no longer being performed as of 1/8/09)

  24 months

Study Arms (2)

Group 1

EXPERIMENTAL

Patients receive cisplatin IV over 1 hour on day 2 of courses 1 and 2 and on day 1 of all subsequent courses; etoposide IV over 30 minutes on days 1-3; and oral sorafenib tosylate once or twice daily on days 1-21. Treatment repeats every 21 days in the absence of unacceptable toxicity or disease progression.

Drug: cisplatin; Drug: etoposide; Drug: sorafenib tosylate

Group 2

EXPERIMENTAL

Patients receive carboplatin IV over 30 minutes and pemetrexed disodium IV over 10 minutes on day 1. Patients also receive sorafenib tosylate as in group 1. Treatment repeats every 21 days in the absence of unacceptable toxicity or disease progression.

Drug: carboplatin; Drug: pemetrexed disodium; Drug: sorafenib tosylate

Interventions

carboplatin DRUG

Given IV

Group 2

cisplatin DRUG

Given IV

Group 1

etoposide DRUG

Given IV

Group 1

pemetrexed disodium DRUG

Given IV

Group 2

sorafenib tosylate DRUG

Given orally

Group 1; Group 2

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed metastatic solid tumor * Disease progressed during at least one standard therapy OR has a disease for which there is no standard therapy * No squamous cell carcinoma of the lung * Asymptomatic brain metastases allowed provided both of the following criteria are met: * Brain metastases were treated ≥ 6 months ago * Brain metastases are clinically stable without steroid treatment for 1 week * No clinically relevant pleural effusions or ascites that cannot be controlled by drainage (group 2) PATIENT CHARACTERISTICS: * ECOG performance status 0-1 * Hemoglobin ≥ 9.0 g/dL * ANC ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Total bilirubin ≤ 1.5 times upper limit of normal (ULN) * ALT and AST ≤ 2.5 times ULN * INR \< 1.5 or PT/PTT normal * Creatinine clearance ≥ 45 mL/min * Negative serum pregnancy test * Fertile patients must use effective contraception during and for at least 2 weeks after completion of study treatment * No New York Heart Association class III or IV congestive heart failure * No unstable angina (anginal symptoms at rest) or new onset angina (within the past 3 months) * No myocardial infarction within the past 6 months * No cardiac ventricular arrhythmias requiring anti-arrhythmic therapy * No uncontrolled hypertension, defined as systolic blood pressure \> 150 mm Hg or diastolic blood pressure \> 90 mm Hg, despite optimal medical management * No known severe hypersensitivity to sorafenib tosylate or any its excipients, etoposide, pemetrexed disodium, cisplatin, or carboplatin * No known HIV infection * No chronic hepatitis B or C * No active clinically serious infection \> CTCAE grade 2 * No thrombotic or embolic events, such as cerebrovascular accident or transient ischemic attacks, within the past 6 months * No pulmonary hemorrhage or bleeding event ≥ CTCAE grade 2 within the past 4 weeks * No other hemorrhage or bleeding event ≥ CTCAE grade 3 within the past 4 weeks * No serious non-healing wound, ulcer, or bone fracture * No evidence or history of bleeding diathesis or coagulopathy * No condition that impairs the patient's ability to swallow whole pills * No malabsorption problem, uncontrolled inflammatory bowel disease, or gastrointestinal disorder causing ≥ 5 bowel movements in a 24-hour period * No significant traumatic injury within the past 4 weeks * Able to take vitamin B12 supplementation and folic acid (group 2) PRIOR CONCURRENT THERAPY: * More than 4 weeks since prior major surgery or open biopsy * No more than 3 prior cytotoxic therapies for metastatic disease * No concurrent St. John's wort or rifampin * No non-steroidal anti-inflammatory drugs (NSAIDs) for 2 days before (5 days for long-acting NSAIDs), during, and for 2 days after pemetrexed disodium administration (group 2) * Concurrent anticoagulation treatment with warfarin or heparin allowed

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599-7295, United States

Location

MeSH Terms

Interventions

Carboplatin; Cisplatin; Etoposide; Pemetrexed; Sorafenib

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Thomas E. Stinchcombe, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

• Elizabeth C. Dees, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2007
• First Posted: December 14, 2007
• Study Start: September 1, 2007
• Primary Completion: June 1, 2009
• Study Completion: February 1, 2011
• Last Updated: April 24, 2012

Record last verified: 2012-04

Locations

US (1)