Rebeccamycin Analog as Second-Line Therapy in Treating Patients With Limited-Stage or Extensive-Stage Small Cell Lung Cancer That Relapsed After Previous First-Line Chemotherapy

Phase II Trial of XL119 (Rebeccamycin Analogue) in Relapsed "Sensitive" Small Cell Lung Cancer

Drugs used in chemotherapy, such as rebeccamycin analog, work in different ways to stop tumor cells from dividing so they stop growing or die. This phase II trial is studying how well rebeccamycin analog works as second-line therapy in treating patients with limited-stage or extensive-stage small cell lung cancer that has relapsed after previous first-line chemotherapy.

Study Overview

• Status: Terminated
• Conditions: Extensive Stage Small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Limited Stage Small Cell Lung Cancer
• Intervention / Treatment: Drug: becatecarin

Detailed Description

OBJECTIVES:

I. Determine the objective response rate in patients with limited or extensive stage small cell lung cancer that relapsed after prior first-line chemotherapy when treated with rebeccamycin analogue as second-line therapy.

II. Determine the duration of remission and survival of patients treated with this drug.

III. Determine the toxicity of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive rebeccamycin analogue IV over 1 hour on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed annually.

PROJECTED ACCRUAL: A total of 20-39 patients will be accrued for this study within 15 months.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of small cell lung cancer (SCLC)

  • Limited or extensive stage
• At least 1 unidimensionally measurable lesion at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
• Sensitive* relapsed disease after only 1 prior chemotherapy regimen

• Brain metastasis allowed provided the following criteria are met:

  • Stable brain disease
  • Not receiving irradiation
  • No steroid requirement to control symptoms
• Performance status - ECOG 0-2
• Performance status - Karnofsky 60-100%
• At least 12 weeks
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9.0 g/dL
• AST and ALT < 2.5 times upper limit of normal (ULN) (5 times ULN if liver involvement is present)
• Bilirubin ≤ 1.5 mg/dL
• Creatinine < 2.0 mg/dL
• Creatinine clearance ≥ 60 mL/min
• No New York Heart Association class III or IV heart disease
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active or ongoing infection
• No other concurrent uncontrolled illness
• No psychiatric illness or social situation that would preclude study compliance
• See Disease Characteristics
• See Disease Characteristics
• See Disease Characteristics
• Prior radiotherapy allowed
• No other concurrent investigational agents
• No other concurrent therapies for SCLC
• No concurrent combination antiretroviral therapy for HIV-positive patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (becatecarin); Patients receive rebeccamycin analogue IV over 1 hour on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Drug: becatecarin; Given IV; Other Names: BMS-181176; rebeccamycin analogue; rebeccamycin analogue, tartrate salt; XL119

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate Estimated as the Proportion of Responders	Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD):At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD):Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. An exact binomial 95% confidence interval will be calculated for this proportion.	Up to 4 years
Progression Free Survival	Median time of patients without Progressive Disease (PD):At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Duration of remission will be analyzed using Kaplan-Meier curves.	Up to 4 years
Overall Survival	Median time of patient survival. Duration of survival will be analyzed using Kaplan-Meier curves.	Up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Percentage of patients that are progression free at 6 months.	6 months
Overall Survival	Percentage of patients alive at 1 year	1 year

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Afshin Dowlati, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: June 10, 2004
• First Submitted That Met QC Criteria: June 10, 2004
• First Posted (Estimate): June 11, 2004

Study Record Updates

• Last Update Posted (Estimate): May 23, 2014
• Last Update Submitted That Met QC Criteria: May 7, 2014
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma
• Other Study ID Numbers: NCI-2012-02587 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U01CA062502 (U.S. NIH Grant/Contract); P30CA043703 (U.S. NIH Grant/Contract); 1990 (CTEP); NCI-1990; CASE-1503; CDR0000365315; CASE-CWRU-1503 (Other Identifier: Case Comprehensive Cancer Center)