Sorafenib, Cisplatin, and Etoposide in Treating Patients With Extensive-Stage Small Cell Lung Cancer

Lung Cancer Clinical Trial

Official title:

Phase II Trial of Sorafenib in Conjunction With Chemotherapy and as Maintenance Therapy in Extensive-Stage Small Cell Lung Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00726986
• Other study ID #: CASE8507
• Secondary ID: P30CA043703CASE8
• Status: Terminated
• Phase: Phase 2
• First received: July 31, 2008
• Last updated: November 5, 2014
• Start date: July 2008
• Est. completion date: July 2012

Study information

• Verified date: November 2014
• Source: Case Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as cisplatin and etoposide, 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 combination chemotherapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving sorafenib together with cisplatin and etoposide works in treating patients with extensive-stage small cell lung cancer.

Description:

OBJECTIVES:

• To evaluate the 1-year progression-free survival of patients with extensive-stage small cell lung cancer treated with sorafenib tosylate in combination with cisplatin and etoposide.

• To evaluate the 1-year overall survival and response rate in these patients.

• To evaluate the safety of these drugs in these patients.

OUTLINE: This is a multicenter study.

Patients receive cisplatin IV over 30-60 minutes on day 1 and etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients also receive oral sorafenib tosylate twice daily beginning on day 1 of course 1 and continuing for up to 1 year in the absence of disease progression or unacceptable toxicity.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 18
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of extensive-stage small cell lung cancer

• No untreated brain metastases

• No active symptoms related to brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• 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 (= 5 times ULN for patients with liver involvement)

• Creatinine = 1.5 times ULN

• INR < 1.5 or PT/PTT normal

• No history of cardiac disease, including any of the following:

• NYHA class III-IV congestive heart failure

• Unstable angina (i.e., anginal symptoms at rest)

• Onset of angina within the past 3 months

• Myocardial infarction within the past 6 months

• No cardiac ventricular arrhythmias requiring anti-arrhythmic therapy

• No uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg or diastolic BP > 90 mm Hg, despite optimal medical management

• No thrombolic or embolic events, such as cerebrovascular accident or transient ischemic attacks, within the past 6 months

• No pulmonary hemorrhage/bleeding event = CTCAE grade 2 within the past 4 weeks

• No other hemorrhage/bleeding event = CTCAE grade 3 within the past 4 weeks

• No known HIV infection or chronic hepatitis B or C infection

• No active clinically serious infection > CTCAE grade 2

• No serious non-healing wound, ulcer, or bone fracture

• No evidence or history of bleeding diathesis or coagulopathy

• No significant traumatic injury within the past 4 weeks

• No known or suspected allergy to sorafenib tosylate or to any other drug given during the study

• No condition that would impair the patient's ability to swallow whole pills

• No known malabsorption problem

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective barrier contraception

• Male patients must use effective contraception during and for = 3 months after completion of sorafenib tosylate

PRIOR CONCURRENT THERAPY:

• Prior radiotherapy to the brain allowed

• No prior chemotherapy

• More than 4 weeks since prior major surgery or open biopsy

• No concurrent Hypericum perforatum (St. John's wort) or rifampin

• Concurrent anti-coagulation treatment, such as warfarin or heparin, allowed

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms
• Small Cell Lung Carcinoma

Intervention

Drug:
• cisplatin
Cisplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
• etoposide
Etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
• sorafenib tosylate
Oral sorafenib tosylate twice daily beginning on day 1 of course 1 and continuing for up to 1 year in the absence of disease progression or unacceptable toxicity.

Locations

Country	Name	City	State
United States	Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center	Cleveland	Ohio
United States	CCF-Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Lake/University Ireland Cancer Center	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Southwest General Health Center	Cleveland	Ohio
United States	UHHS Chagrin Highlands Medical Center	Cleveland	Ohio
United States	UHHS Westlake Medical Center	Cleveland	Ohio
United States	UH-Monarch	Mayfield Heights	Ohio
United States	Columbia Presbyterian	New York	New York
United States	UH-Firelands	Sandusky	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Afshin Dowlati, MD	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival(PFS)	PFS is defined as the duration of time from start of treatment to time of progression or death, whichever comes first.	1-year	No
Secondary	Median Overall Survival	Overall survival is measured from the date of chemotherapy treatment (date of cycle 1 of induction chemotherapy) until death and censored at the date of last follow-up for survivors.	1-year	No
Secondary	Response Rate	The Response Evaluation Criteria in Solid Tumors (RECIST) were used to assess response to the treatment.; Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started	reevaluated for response every 8 weeks	No
Secondary	Safety	Number of patients that experienced grade 3-4-5 treatment related toxicities. Toxicity was graded by the National Cancer Institute Common Terminology Criteria version 3.0.	Treatment repeats every 21 days for 4 courses in the absence of unacceptable toxicity.	Yes