Study in Patients With Advanced Non-Small Cell Lung Cancer Treated With Pemetrexed and Carboplatin Plus or Minus Sorafenib (PECASO)

University Hospital Muenster

Status and phase

Terminated

Phase 2

Phase 1

Conditions

Carcinoma, Non-Small-Cell Lung

Treatments

Drug: pemetrexed, carboplatin, sorafenib

Drug: pemetrexed, carboplatin, placebo

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00473486

2006-005970-26

KKS / INNERE_A / NSCLC2006

Details and patient eligibility

About

The majority of patients with advanced NSCLC treated with standard platinum based chemotherapy regimens ultimately develop disease progression. Active therapies with improved toxicity profiles are clearly needed in this setting. The primary objective of this trial is to assess the toxicity profile and to determine the effect on progression free survival and time to progression in patients with advanced NSCLC treated with sorafenib in addition to carboplatin and pemetrexed.

Enrollment

12 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Histologically or cytologically confirmed NSCLC
Locally advanced (stage IIIB with malignant pleural or pericardial effusion) or metastatic (stage IV) NSCLC
No prior systemic chemotherapy
Prior local radiotherapy is allowed if it is completed at least 3 weeks prior to the first dose of study medication; also concomitant palliative radiotherapy to an existing bone lesion for pain control is allowed
Prior surgery is allowed if it is performed at least 4 weeks prior to the first dose of study medication and patient should be fully recovered.
Must have measurable disease with at least one lesion with a longest diameter measured as ≥ 2 cm with conventional techniques or as ≥ 1 cm with spiral CT
Age ≥18 years old
ECOG performance score (PS) 0-1
Life expectancy of at least 12 weeks
Adequate bone marrow, renal and hepatic function
- hemoglobin ≥ 9.0 g/dl
- absolute neutrophil count ≥1,500/mm3
- platelet count ≥ 100,000/mm3
- total bilirubin ≤ 1.5 times the upper limit of normal
- ALT and AST ≤ 2.5 times the upper limit of normal (≤ 5 x upper limit of normal for patients with liver involvement)
- INR ≤ 1.5 and aPTT within normal limits
- serum creatinine ≤ 1.5 the upper limit of normal
Patients with creatinine clearance ≥ 45 mL/min
Not pregnant or nursing patients
Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men should use adequate birth control for at least six months after the last administration of sorafenib
Signed informed consent prior to any study specific procedures
Compliance and geographic proximity that allow adequate follow-up

Exclusion criteria

Any prior systemic anticancer therapy including cytotoxic therapy, targeted agents, experimental therapy (treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study enrollment), adjuvant, or neo-adjuvant therapy for NSCLC
Any participation in a clinical trial 30 days prior to study entry and concomitantly to the study
Cardiac disease: Congestive heart failure > class II NYHA. Patients must not have unstable angina (angina symptoms at rest) or new-onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg or diastolic pressure > 90 mm Hg, despite optimal medical management
Documented brain metastases (unless the patient is > 6 months from definitive therapy for brain metastases, has a negative imaging study within 4 weeks of study entry and has been off corticosteroids for at least 4 weeks before study enrolment). Brain imaging (CT scan/MRI) is required in symptomatic patients to rule out brain metastases, but is not required in asymptomatic patients.
Patients with seizure disorder requiring medication (such as steroids or antiepileptics)
Known HIV infection or chronic hepatitis B or C
Active clinically serious infections > CTCAE Grade 2
Presence of clinically significant third-space fluid collections, for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study enrolment
Pulmonary hemorrhage/bleeding event >= CTCAE Grade 2 within 4 weeks of first dose of study drug
Any other hemorrhage/bleeding event > =Grade 3 within 4 weeks of first dose of study drug
Evidence or history of bleeding diathesis or coagulopathy
Therapeutic anticoagulation with vitamin K antagonists such as phenprocoumon, warfarin, or with heparins or heparinoids. Low dose anticoagulation is permitted
Serious, non-healing wound, ulcer, or bone fracture
Major surgery, open biopsy or significant traumatic injury within 4 weeks of first dose of study drug
Known or suspected allergy to sorafenib, carboplatin or pemetrexed
Previous or current cancer that is distinct in primary site or histology from NSCLC except cervical cancer in-situ, treated basal cell carcinoma, superficial bladder tumors (Ta and Tis) or any cancer curatively treated > 3 years prior to study entry
Substance abuse, medical, psychological or social conditions that may interfere with the patients participation in the study
Significant weight loss (> or equal 10% body weight during preceeding 6 weeks)
Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents, other than an aspirin dose ≤ 1.3 grams per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam)
Inability or unwillingness to take folic acid, vitamin B12 supplementation or corticosteroids
Recent (within 30 days of enrolment) or concurrent yellow fever vaccination
Serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the patient's ability to adhere to the protocol.