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

December 14, 2012 updated by: Peking Union Medical College Hospital

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

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.

Study Overview

Status

Unknown

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Anticipated)

60

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • Beijing
      • Beijing, Beijing, China, 100730
        • Recruiting
        • Department of Respiratory Medicine, Peking Union Medical College Hospital
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Wei Zhong, MD
        • Sub-Investigator:
          • Jinmei Luo, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

ED-SCLC patients who relapse after treatment with first-line EP or CE and second-line topotecan.

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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);
vinorelbine 25mg/m2 d1,d8; ifosfamide 1.25g/m2 d1-d3; Mesna 400mg iv 0,4,8 hours after ifosfamide administration for 3 days
Other Names:
  • vinorelbine;
  • ifosfamide;
  • Mesna;

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
the disease control rate
Time Frame: up to 9 weeks
The disease control rate includes the rate of progression disease,partial remission and stable disease.
up to 9 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
progression free survival
Time Frame: up to 52 weeks (about one year)
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)
Overall survival
Time Frame: Up to 100 weeks
From date of randomization until the date of death from any cause, assessed up to 100 weeks.
Up to 100 weeks
the score of functional assessment of cancer treatment-lung (FACT-L)
Time Frame: up to 52 weeks
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
Number of participants with adverse events
Time Frame: Up to six months
The adverse events are assessed by National Cancer Institute-Common Toxicity Criteria (Version 3.0)(NCI-CTC).
Up to six months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Mengzhao Wang, MD, Peking Union Medical College Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2012

Primary Completion (Anticipated)

December 1, 2014

Study Completion (Anticipated)

December 1, 2015

Study Registration Dates

First Submitted

December 12, 2012

First Submitted That Met QC Criteria

December 14, 2012

First Posted (Estimate)

December 19, 2012

Study Record Updates

Last Update Posted (Estimate)

December 19, 2012

Last Update Submitted That Met QC Criteria

December 14, 2012

Last Verified

December 1, 2012

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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