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A Phase II Study of Sunitinib as a Second-line Treatment for Patients With Recurrent Small Cell Lung Cancer.

Phase 2
18 Years
Not Enrolling
Lung Cancer

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Trial Information

A Phase II Study of Sunitinib as a Second-line Treatment for Patients With Recurrent Small Cell Lung Cancer.

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

Inclusion Criteria:

1. Histologic or cytologic confirmed SCLC

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

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

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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Tumor response rate

Outcome Description:

The response rate will be determined by the number of patients with complete and partial responses according to RECIST criteria.

Outcome Time Frame:

at 4week and every 8 weeks

Safety Issue:


Principal Investigator

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

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Center, Korea


South Korea: Korea Food and Drug Administration (KFDA)

Study ID:




Start Date:

March 2008

Completion Date:

September 2012

Related Keywords:

  • Lung Cancer
  • SCLC (small cell lung cancer)
  • ED (extensive disease)
  • RR (response rate)
  • Lung Neoplasms
  • Small Cell Lung Carcinoma