A Randomized Phase II Study of Sorafenib Maintenance in Patients With Extensive Disease Small Cell Lung Cancer (ED-SCLC) After Response to Induction Chemotherapy
- Histologically or cytologically confirmed ED-SCLC patients who have achieved a
complete or partial response after four to six cycles of platinum based induction
- Extensive stage SCLC is defined as disease not meaning the definition of limited
- Previous radiotherapy is allowed only if < 30% of marrow bearing bones were
irradiated and if radiotherapy was completed at least 2 weeks prior to enrollment and
the patient has recovered from all adverse effects of prior radiotherapy.
- Age >18 years.
- Written informed consent that is consistent with ICH-GCP guidelines
- Life expectancy of greater than 3 months.
- ECOG performance status 2 (Karnofsky ≥50%).
- Ability to swallow oral medication
- Women of childbearing potential must have a negative serum pregnancy test performed
within 7 days prior to the start of treatment
- Both men and women enrolled in this trial must use adequate barrier birth control
measures during the course of the trial and during the first 3 months after the
completion of trial
- Adequate bone marrow, liver and renal function
- History of cardiac disease/ HIV infection / chronic hepatitis B or C / of organ
- Active clinically serious infections
- Patients with seizure disorder requiring medication or evidence or history of
bleeding diathesis or coagulopathy
- Patients undergoing renal dialysis
- Pulmonary hemorrhage/ bleeding event ≥ CTCAE grade 2 within four weeks
- Any other hemorrhage/ bleeding event ≥ CTCAE grade 3 within four weeks
- Non-healing wound, ulcer or bone fracture
- Thrombotic or embolic venous or arterial events of study drug
- Previous or concurrent cancer that is distinct in histology of primary site, EXCEPT
cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors
(Ta, Tis, T1). Any cancer curatively treated >3 years prior to entry is permitted.
- Substance abuse, medical, psychological or social conditions that may interfere with
the subject's participation in the study or evaluation of the study results
- Known or suspected allergy or any other contraindication for Sorafenib administration
- Pregnant or breast-feeding women.
- Any disease which could affect the evaluation of the study drug
- Any condition that is unstable or could jeopardize the safety of the subject and
their compliance in the study
- Any condition which could affect the absorption or pharmacokinetics of the Study drug
including any type of gastrointestinal resection or surgery
- Uncontrolled symptomatic brain metastasis
Excluded therapies and medications, previous and concomitant:
- Investigational drug or device therapy including outside of this trial during or
within 4 weeks prior to study entry (signing Informed Consent).
- The toxicity effects of previous antitumor chemotherapy or immunotherapy must be
resolved to less than CTC Grade 2 level (exception: alopecia).
- Prior treatment with other VEGFR inhibitors (i.e. sunitinib, thalidomide, vandetanib
and other experimental agents of this class).
- Major surgery within 4 weeks prior to start of study (Informed Consent signature).
Minimal invasive biopsy is allowed.
- Use of biologic response modifiers, such as G-CSF, within 3 weeks prior to study
entry. [Therapeutic G-CSF and other hematopoietic growth factors may be used in the
management of acute toxicity such as febrile neutropenia when clinically indicated or
at the discretion of the investigator, however they may not be substituted for a
required dose reduction].
- Any agents which could affect the absorption or pharmacokinetics of the study drug
- Prior exposure to the study drug
- Therapeutic anticoagulation with vitamin K antagonists such as warfarin, or with
heparins or heparinoids. Prophylactic low dose warfarin (1 mg po qd) is permitted if
the INR (International normalized ratio) is ≤ 1.5. Low-dose aspirin is permitted
(80-100 mg daily).