Sunitinib as a Second-line Treatment for Patients With Recurrent Small Cell Lung Cancer

NCT ID: NCT00620347

Last Updated: 2013-06-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-31
• Study Completion Date: 2012-09-30

Brief Summary

the investigators will conduct a phase II trial to evaluate the efficacy and toxicity of Sunitinib in patients with recurrent SCLC.

Detailed Description

Chemotherapy is the primary treatment option for patients with small cell lung cancer, leading to a 5-year survival of about 20% in limited disease (LD), and less than 5% in extensive disease (ED). Although initial tumor response rate to chemotherapy is very high (up to 96% for LD and up to 65% in ED), SCLC relapses in approximately 4 months in ED and 12 months in LD adn despite the administration of second-line chemotherapy, the overall median survival of patients with limited and extensive disease is approximately 18 and 9 months, respectively. In the setting of second-line therapy, response rates to chemotherapy range between 15 and 25%, with median survival in the range of 4-6 months. Second-line therapeutic options include cyclophosphamide, doxorubicin and vincristine (CAV) given every 3 weeks or topotecan, which have similar response rates, time to progression and survival in the two treatment arms (topotecan 24%, 13 and 24.7 weeks; CAV 18%, 12 and 22 weeks, respectively). However, both treatments however have substantial toxicities, with 9% of patients on trial withdrawing for toxicity reasons. Treatment-associated mortality was as high as 4.7% (possibly and definitely related), and many patients required transfusion support. Thus, while these treatments have acceptable activity second-line, more active and less toxic treatments are required for this patient population.Tyrosine kinase inhibitors have become a promising new class of anti-cancer agents owing to the importance of their targets in tumor proliferation, survival (apoptosis), angiogenesis, motility, and metastasis Among the most important receptor tyrosine kinases that regulate tumor angiogenesis are the vascular endothelial growth factor receptor 2 (VEGFR2/Flk-1/KDR), PDGFR, and the fibroblast growth factor (FGF) receptor family. These receptors belong to the split-kinase domain superfamily, which also includes Kit, the receptor for stem cell factor (SCF). Kit is frequently expressed in multiple hematologic and non-hematologic malignancies. It can also be activated in an autocrine fashion by coexpression with SCF, as is the case in SCLC, where approximately 70% of tumors and cell lines coexpress Kit and SCF at some level. Inhibition of Kit using small molecule inhibitors results in growth inhibition of multiple SCLC cell lines. Sunitinib, a novel small molecule receptor tyrosine kinase inhibitor with direct antitumor as well as antiangiogenic activity via targeting the vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), KIT, and FLT3 receptor tyrosine kinases, which showed anti-tumor activity in mouse xenograft model of SCLC. Therefore, the investigators will conduct a phase II trial to evaluate the efficacy and toxicity of Sunitinib in patients with recurrent SCLC.-Single arm

-Sunitinib(50mg/day, 4weeks on, 2 weeks off) Repeat every 6 weeksTreatment will continue until disease progression, unacceptable toxicity, or patients' refusal

Conditions

Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single arm

Single arm (sunitinib arm) until PD, unacceptable toxicity, patients refused

Group Type: EXPERIMENTAL

sunitinib

Intervention Type: DRUG

sunitinib (50mg/day, 4weeks on, 2 weeks off) Repeat every 6 weeks. Treatment will continue until disease progression, unacceptable toxicity, or patients' refusal.

Interventions

sunitinib

sunitinib (50mg/day, 4weeks on, 2 weeks off) Repeat every 6 weeks. Treatment will continue until disease progression, unacceptable toxicity, or patients' refusal.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Histologic or cytologic confirmed SCLC

2. Clinically diagnosed ED-SCLC according to sixth Edition of the AJCC cancer staging manual

3. Progression during or after prior first line chemotherapy.

4. Resolution of all acute toxic effects of prior therapy or surgical procedure to grade ≤ 1 (except alopecia)

5. Prior radiation therapy excluded lung is allowed.

6. No other forms of cancer therapy, such as chemotherapy, radiation, immunotherapy for at least 3 weeks before the enrollment in study.

7. Performance status of 0, 1, 2 on the ECOG criteria.

8. Tumor work-up: within 4weeks prior 1st day of treatment: chest X-ray; CT of chest, liver, and adrenal glands; bone scan; brain MRI

9. At least one uni-dimensionally measurable lesion meeting Response Evaluation Criteria in Solid Tumors.

10. Estimated life expectancy of at least 12 weeks.

11. Patient compliance that allows adequate follow-up.

12. Adequate organ function for chemotherapy

13. Adequate cardiac function: normal EF by Echocardiography

14. No ischemic heart disease or cardiac dysrhythmia.

15. Normal QTc interval

16. Normal thyroid function.

17. Informed consent from patient or patient's relative.

18. Males or females at least 18 years of age.

19. If female: childbearing potential either terminated by surgery, radiation, or menopause, or attenuated by use of an approved contraceptive method (intrauterine device [IUD], birth control pills, or barrier device) during and for 3 months after trial. If male, use of an approved contraceptive method during the study and 3 months afterwards. Females with childbearing potential must have a urine negative HCG test within 7 days prior to the study enrollment.

Exclusion Criteria

1. Diagnosis of any second malignancy within the past 3 years, except basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma that has been adequately treated with no evidence or recurrent disease for 12 months

2. NCI CTCAE grade ≥ 2 neuropathy from any cause

3. Ongoing treatment with therapeutic doses of coumarin derivatives, such as warfarin, (low dose Coumadin® up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed)

4. Uncontrolled brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease. Patients should have completed surgery or radiation therapy for existing brain metastases, should not have documented increase in size over the previous 3 months and should be asymptomatic off steroids

5. Any of the following within the 12 months prior to starting study treatment: myocardial infarction, sever/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident including transient ischemic attack, or pulmonary embolus

6. NCI CTCAE Grade 3 hemorrhage < 4 weeks of starting study treatment

7. Hypertension (>150/100 mg Hg) that cannot be controlled with standard antihypertensive agents

8. Ongoing cardiac dysrhythmias of grade ≥ 2, atrial fibrillation of any grade, or QTc interval > 450 msec for males or > 470 msec for female

9. Known human immunodeficiency virus (HIV) seropositivity

10. Pregnancy or breastfeeding. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) within 7 days prior to enrolment

11. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

National Cancer Center, Korea

OTHER_GOV

Sponsor Role: lead

Responsible Party

Ji-youn Han

Head, Center for Lung Cancer

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ji-Youn Han, M.D.,Ph.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Center, Korea

Locations

National Cancer Center, Korea

Goyang-si, Gyeonggi-do, South Korea

Countries

South Korea

References

Han JY, Kim HY, Lim KY, Han JH, Lee YJ, Kwak MH, Kim HJ, Yun T, Kim HT, Lee JS. A phase II study of sunitinib in patients with relapsed or refractory small cell lung cancer. Lung Cancer. 2013 Feb;79(2):137-42. doi: 10.1016/j.lungcan.2012.09.019. Epub 2012 Nov 20.

Reference Type: DERIVED

PMID: 23182663 (View on PubMed)

Other Identifiers

NCCCTS-07-285

Identifier Type: -

Identifier Source: org_study_id