Vinorelbine and Ifosfamide as Third-line Treatment for Refractory Small Cell Lung Cancer

Small Cell Lung Cancer Clinical Trial

Official title:

A Phase Ⅱ Single-arm Clinical Trial to Investigate the Efficacy and Safety of Vinorelbine-ifosfamide Regimen as Third-line Treatment in Refractory or Recurrent Extensive Small Cell Lung Cancer Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01752517
• Other study ID #: PUMCH-S463
• Status: Recruiting
• Phase: N/A
• First received: December 12, 2012
• Last updated: December 14, 2012
• Start date: December 2012
• Est. completion date: December 2015

Study information

• Verified date: December 2012
• Source: Peking Union Medical College Hospital
• Contact: Mengzhao Wang, MD
• Phone: 010-69155039
• Email: mengzhaowang[@]sina.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Observational

Clinical Trial Summary

Although fist-line therapy with Cisplatin and etoposide(EP)or Carboplatin and etoposide(CE)and second-line therapy with topotecan has been given, patients with ED-SCLC still relapse and 2-year survival is less than 10%. There is no standard treatment recommendation for this group of patients who failed to second-line therapy and had good performance status. Some cytotoxic drugs for the treatment of non-small cell lung cancer, i.e. vinorelbine, paclitaxel, and ifosfamide, were used in refractory or recurrent SCLC patients. Recently, a retrospective study showed the overall response rate was 30%, the median progression free survival (PFS) was 6.5 months, and the median overall survival was 10.4 months in advanced combined SCLC patients treated with first-line regimen of vinorelbine, ifosfamide and cisplatin (NIP). Because of the previous platinum administration and patient's performance status, only vinorelbine and ifosfamide (NI) are combined and used as third-line therapy for refractor or recurrent ED-SCLC in our lung cancer center. And this clinical trial is designed to prospectively investigate the efficacy and safety of NI regimen in refractory or recurrent ED-SCLC patients in our center.

Description:

Small cell lung cancer (SCLC) is a highly aggressive disease characterized by its rapid doubling time, high growth fraction, early development of disseminated disease, and dramatic response to first-line chemotherapy and radiation. Small cell lung cancer accounts for approximately 20%-25% lung cancer patients. SCLC patients are categorized as limited disease, defined as disease that is confined to the ipsilateral hemithorax that can be encompassed within a tolerable radiation port, or extensive disease (ED), defined as the presence of overt metastatic disease determined by imaging or physical examination. Two third of patients are diagnosed with ED at presentation. Despite the development of novel cytotoxic drugs, the therapeutic approach to SCLC has been stagnant for more than twenty years. Standard treatment for ED-SCLC remains EP or CE, a regimen that yield a median survival of approximately 9 months and a 5-year survival of less than 1%.

Most patients are destined to relapse, and the prognosis for this group of patients who relapse is poor. Patients who relapse < 3 months after first-line therapy are commonly called refractory, and patients who relapse 3 months after therapy are labeled as sensitive. In a randomized multicenter study, von Pawel et al compared cyclophosphamide, adriamycin, and vincristine (CAV) with topotecan as a single agent in patients who had relapse at least 60 days (2 months) after initial therapy. The response rates were 24.3% in patients treated with topotecan and 18.3% in patients treated with CAV (P=0.285). Median times to progression were 13.3 weeks for the topotecan arm and 12.3 weeks for the CAV arm. Median survival times were 25 weeks for topotecan and 24.7 weeks for CAV. The proportion of patients with symptom improvement was greater in the topotecan arm than in the CAV arm. The authors concluded that topotecan was at least as effective as CAV in the treatment of patients with recurrent SCLC. So in some guidelines for SCLC, topotecan is recommended as the standard second-line treatment in patients who relapse less than 3 months. As for patients who relapse more than six months after the end of initial treatment, EP or CE regimen is recommended to be used again.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• histologically or cytologically confirmed ED-SCLC;

• age>18 and <75;

• measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST);

• previous treatments including first-line therapy with EP or CE and second-line therapy with topotecan;

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2;

• life expectancy > 3 months;

• neutrophil count > 1500/ul;

• platelet count > 100,000ul;

• hemoglobin level > 9g/dl;

• bilirubin level < 1.5mg/dL;

• creatinine level < 2mg/dl;

• alanine transaminase (AST) levels < 2.5× upper limit of normal (ULN)(or < 5× ULN if liver metastases were present);

Exclusion Criteria:

• previous anticancer therapy including vinorelbine or ifosfamide;

• newly diagnosed central nervous system (CNS) metastasis and not treated by radiotherapy or surgery;

• additional malignancies;

• uncontrolled systemic disease;

• pregnancy or breast feeding phase;

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Drug:
• NI group
vinorelbine 25mg/m2 d1,d8; ifosfamide 1.25g/m2 d1-d3; Mesna 400mg iv 0,4,8 hours after ifosfamide administration for 3 days

Locations

Country	Name	City	State
China	Department of Respiratory Medicine, Peking Union Medical College Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

References & Publications (9)

Clark R, Ihde DC. Small-cell lung cancer: treatment progress and prospects. Oncology (Williston Park). 1998 May;12(5):647-58; discussion 661-3. Review. — View Citation

Fukuoka M, Furuse K, Saijo N, Nishiwaki Y, Ikegami H, Tamura T, Shimoyama M, Suemasu K. Randomized trial of cyclophosphamide, doxorubicin, and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer. J Nat — View Citation

Jackman DM, Johnson BE. Small-cell lung cancer. Lancet. 2005 Oct 15-21;366(9494):1385-96. Review. — View Citation

Luo J, Wu FY, Li AW, Zheng D, Liu JM. Comparison of vinorelbine, ifosfamide and cisplatin (NIP) and etoposide and cisplatin (EP) for treatment of advanced combined small cell lung cancer (cSCLC) patients: a retrospective study. Asian Pac J Cancer Prev. 20 — View Citation

Roth BJ, Johnson DH, Einhorn LH, Schacter LP, Cherng NC, Cohen HJ, Crawford J, Randolph JA, Goodlow JL, Broun GO, et al. Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alternation of these two regi — View Citation

Simon GR, Turrisi A; American College of Chest Physicians. Management of small cell lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest. 2007 Sep;132(3 Suppl):324S-339S. — View Citation

Skarlos DV, Samantas E, Kosmidis P, Fountzilas G, Angelidou M, Palamidas P, Mylonakis N, Provata A, Papadakis E, Klouvas G, et al. Randomized comparison of etoposide-cisplatin vs. etoposide-carboplatin and irradiation in small-cell lung cancer. A Hellenic — View Citation

von Pawel J, Schiller JH, Shepherd FA, Fields SZ, Kleisbauer JP, Chrysson NG, Stewart DJ, Clark PI, Palmer MC, Depierre A, Carmichael J, Krebs JB, Ross G, Lane SR, Gralla R. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment — View Citation

Wolf M, Havemann K, Holle R, Gropp C, Drings P, Hans K, Schroeder M, Heim M, Dommes M, Mende S, et al. Cisplatin/etoposide versus ifosfamide/etoposide combination chemotherapy in small-cell lung cancer: a multicenter German randomized trial. J Clin Oncol. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the disease control rate	The disease control rate includes the rate of progression disease,partial remission and stable disease.	up to 9 weeks	No
Secondary	progression free survival	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks.	up to 52 weeks (about one year)	No
Secondary	Overall survival	From date of randomization until the date of death from any cause, assessed up to 100 weeks.	Up to 100 weeks	No
Secondary	the score of functional assessment of cancer treatment-lung (FACT-L)	FACT-L ia assessed at different time points. (Date of randomization, 1 weeks after chemotherapy, every cycle of chemotherapy, every month after chemotherapy,up to 52 weeks)	up to 52 weeks	No
Secondary	Number of participants with adverse events	The adverse events are assessed by National Cancer Institute-Common Toxicity Criteria (Version 3.0)(NCI-CTC).	Up to six months	Yes