Sorafenib Combined With Cisplatin and Etoposide or Carboplatin and Pemetrexed in Treating Patients With Metastatic Solid Tumors - Full Text View

Purpose

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.

Condition	Intervention	Phase
Unspecified Adult Solid Tumor, Protocol Specific	Drug: carboplatin Drug: cisplatin Drug: etoposide Drug: pemetrexed disodium Drug: sorafenib tosylate	Phase 1


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Two Arm Phase I Trial of Sorafenib in Combination With Cisplatin/Etoposide or Carboplatin/Pemetrexed in Patients With Solid Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Cisplatin Etoposide Carboplatin Etoposide phosphate Pemetrexed Pemetrexed disodium Sorafenib Sorafenib tosylate

U.S. FDA Resources

Further study details as provided by UNC Lineberger Comprehensive Cancer Center:

Primary Outcome Measures:

Recommended phase II dose and maximum tolerated dose of sorafenib tosylate when administered in combination with cisplatin and etoposide or carboplatin and pemetrexed disodium [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Toxicity [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Efficacy of treatment as measured by RECIST criteria or by tumor markers [ Time Frame: 36 months ] [ Designated as safety issue: No ]
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) [ Time Frame: 24 months ] [ Designated as safety issue: No ]


Enrollment:	31
Study Start Date:	September 2007
Study Completion Date:	February 2011
Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Group 1 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 Given IV Drug: etoposide Given IV Drug: sorafenib tosylate Given orally
Experimental: Group 2 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 Given IV Drug: pemetrexed disodium Given IV Drug: sorafenib tosylate Given orally

Detailed Description:

OBJECTIVES:

Primary

To determine the recommended phase II dose and maximum tolerated dose of sorafenib tosylate when administered in combination with cisplatin and etoposide or carboplatin and pemetrexed disodium in patients with metastatic solid tumors.

Secondary

To characterize the toxicities of these regimens in these patients.
To evaluate the efficacy of these regimens in these patients, as measured by RECIST criteria or by tumor markers, if applicable (e.g., PSA, CA-125).
To determine the pharmacokinetics of sorafenib tosylate when administered in combination with etoposide in these patients (samples are no longer being collected and studies are no longer being performed as of 1/8/09).

OUTLINE: Patients are assigned to 1 of 2 treatment groups.

Group 1: 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.
Group 2: 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.

Patients in group 1 undergo blood sample collection on day 1 of courses 1 and 2 for pharmacokinetic studies (samples are no longer being collected and studies are no longer being performed as of 1/8/09).

After finishing treatment, patients are followed at 30 days.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00573690

Locations


United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295

Sponsors and Collaborators

UNC Lineberger Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Thomas E. Stinchcombe, MD	UNC Lineberger Comprehensive Cancer Center
Principal Investigator:	Elizabeth C. Dees, MD	UNC Lineberger Comprehensive Cancer Center

More Information


Responsible Party:	UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00573690 History of Changes
Other Study ID Numbers:	LCCC 0613 CDR0000579819 UNC-LCC-07-0971
Study First Received:	December 13, 2007
Last Updated:	April 20, 2012
Health Authority:	United States: Federal Government

Keywords provided by UNC Lineberger Comprehensive Cancer Center:


unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:


Sorafenib Etoposide phosphate Cisplatin Carboplatin Etoposide Pemetrexed Niacinamide Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action	Vitamin B Complex Vitamins Micronutrients Growth Substances Physiological Effects of Drugs Antineoplastic Agents, Phytogenic Topoisomerase II Inhibitors Topoisomerase Inhibitors Folic Acid Antagonists Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on September 23, 2016