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

NCT ID: NCT01752517

Last Updated: 2012-12-19

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2015-12-31

Brief 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.

Detailed 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.

Conditions

Small Cell Lung Cancer

Keywords

small cell lung cancer; chemotherapy; vinorelbine; ifosfamide; third-line treatment

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

refractory SCLC

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; every 3 weeks; up to the maximum cycles (total:6);

NI group

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

vinorelbine; ifosfamide; Mesna;

Eligibility Criteria

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;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking Union Medical College Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mengzhao Wang, MD

Role: PRINCIPAL_INVESTIGATOR

Peking Union Medical College Hospital

Locations

Department of Respiratory Medicine, Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Mengzhao Wang, MD

Role: CONTACT

Phone: 010-69155039

Email: mengzhaowang@sina.com

Jing Zhao, MD

Role: CONTACT

Phone: 010-69158206

Email: pumchzj@sina.com

Facility Contacts

Mengzhao Wang, MD

Role: primary

Jing Zhao, MD

Role: backup

References

Jackman DM, Johnson BE. Small-cell lung cancer. Lancet. 2005 Oct 15-21;366(9494):1385-96. doi: 10.1016/S0140-6736(05)67569-1.

Reference Type: RESULT

PMID: 16226617 (View on PubMed)

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. doi: 10.1378/chest.07-1385.

Reference Type: RESULT

PMID: 17873178 (View on PubMed)

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

Reference Type: RESULT

PMID: 9597676 (View on PubMed)

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 Natl Cancer Inst. 1991 Jun 19;83(12):855-61. doi: 10.1093/jnci/83.12.855.

Reference Type: RESULT

PMID: 1648142 (View on PubMed)

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. 1987 Dec;5(12):1880-9. doi: 10.1200/JCO.1987.5.12.1880.

Reference Type: RESULT

PMID: 2824710 (View on PubMed)

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 regimens in extensive small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol. 1992 Feb;10(2):282-91. doi: 10.1200/JCO.1992.10.2.282.

Reference Type: RESULT

PMID: 1310103 (View on PubMed)

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 Co-operative Oncology Group study. Ann Oncol. 1994 Sep;5(7):601-7. doi: 10.1093/oxfordjournals.annonc.a058931.

Reference Type: RESULT

PMID: 7993835 (View on PubMed)

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 of recurrent small-cell lung cancer. J Clin Oncol. 1999 Feb;17(2):658-67. doi: 10.1200/JCO.1999.17.2.658.

Reference Type: RESULT

PMID: 10080612 (View on PubMed)

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. 2012;13(9):4703-6. doi: 10.7314/apjcp.2012.13.9.4703.

Reference Type: RESULT

PMID: 23167406 (View on PubMed)

Other Identifiers

PUMCH-S463

Identifier Type: -

Identifier Source: org_study_id