Study of Sorafenib Maintenance in Patients With ED-SCLC After Response to Induction Chemotherapy

National Cancer Center (NCC)

Status and phase

Terminated

Phase 2

Conditions

Small Cell Lung Cancer

Treatments

Drug: Sorafenib

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01159327

NCCCTS-10-476

Details and patient eligibility

About

A Phase I trial of weekly topotecan in combination with sorafenib in treatment of relapsed Small cell lung cancer (SCLC) has been commenced. In the present randomized phase 2 study, the investigators will research whether Sorafenib maintenance prolongs progression free survival (PFS) and overall survival (OS) in patients with ED-SCLC who achieved CR or PR after platinum-based induction chemotherapy.

Full description

Small cell lung cancer (SCLC) comprises 10-15 % of all lung cancer. Despite high responsiveness to initial chemotherapy, its high relapse rate makes the treatment of SCLC is challenging. With platinum plus etoposide or irinotecan, overall response rate is as high as 85%, however, the median duration of response is short (approximately 4 months), and median survival times are 9 to 11 months, with a 2-year survival rate of less than 10% [J Clin oncology. 2009 Oct 1;27(28):4787-92]. New and more effective agents are clearly needed against SCLC. Sorafenib is a multikinase inhibitors acting on pathways involved in tumour progression and angiogenesis, and is undergoing investigation for the treatment of SCLC in either the first- or second-line setting. The only data available so far are on sorafenib, which seems to be a promising agent with a median survival of 7 and 5 months in platinum-sensitive and platinum-refractory patients, respectively (2008 J Clin oncology 26. Abstract 8039). This compared favourably with historical controls receiving salvage chemotherapy.

Enrollment

13 patients

Sex

All

Ages

18+ months old

Volunteers

No Healthy Volunteers

Inclusion criteria

Histologically or cytologically confirmed ED-SCLC patients who have achieved a complete or partial response after four to six cycles of platinum based induction chemotherapy.
Extensive stage SCLC is defined as disease not meaning the definition of limited stage disease
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

Exclusion criteria

History of cardiac disease/ HIV infection / chronic hepatitis B or C / of organ allograft
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).