| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Treatment of metastacic non small cell lung cancer (NSCLC) stage IIIB / IV |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061873 |
| E.1.2 | Term | Non-small cell lung cancer |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
During Phase I, the primary objective is to identify the tolerable recommended doses for combination therapy with carboplatin, pemetrexed and sorafenib for the phase II part.
During Phase II, the primary endpoint is to compare the progression-free survival (PFS) of carboplatin/pemetrexed + sorafenib with carboplatin/pemetrexed + placebo in patients with stage IIIb or IV non-small cell lung cancer. |
|
| E.2.2 | Secondary objectives of the trial |
During Phase I the secondary endpoints are to determine dose limiting toxicities, determine the safety profile of the combination treatment and a descriptive analysis of efficacy.
During Phase II the Secondary objectives are to assess time to progression in patients treated with both regimens, to determine the overall survival in patients treated with both regimens, to determine the objective response rate (CR, PR), disease control rate (CR,PR,SD) and time to response and duration of response, to identify surrogate markers from the tumor biopsy or resection specimen from the time of diagnosis that predict response, to assess Quality of Life of patients treated with both regimen and to assess feasibility and toxicity profile of this regimen. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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
o hemoglobin ≥ 9.0 g/dl
o absolute neutrophil count ≥1,500/mm3
o platelet count ≥ 100,000/mm3
o total bilirubin ≤ 1.5 times the upper limit of normal
o ALT and AST ≤ 2.5 times the upper limit of normal (≤ 5 x upper limit of
normal for patients with liver involvement)
o INR ≤ 1.5 and aPTT within normal limits
o 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
• Estimated life expectancy of at least 12 weeks.
• Compliance and geographic proximity that allow adequate follow-up.
|
|
| E.4 | Principal 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 has completed
successful local therapy for brain metastases 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.
• 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 or vitamin B12 supplementation.
• 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.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Phase I
primary endpoint
• Identify the recommended phase II dose of sorafenib for combination
therapy with carboplatin and pemetrexed
Phase II
primary endpoint
• Compare the PFS of carboplatin/pemetrexed + sorafenib or
carboplatin/pemetrexed + placebo in patients with stage IIIb or IV non-
small cell lung cancer
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
|
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Phase I: open, non-randomised / Phase II: double blind, randomised |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | 0 |
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