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Cisplatin + Etoposide +/- Concurrent ZD6474 in Previously Untreated Extensive Stage Small Cell Lung Cancer

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Hoosier Cancer Research Network
ClinicalTrials.gov Identifier:
NCT00613626
First received: January 31, 2008
Last updated: October 19, 2015
Last verified: October 2015
Results First Received: August 31, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver);   Primary Purpose: Treatment
Condition: Small Cell Lung Cancer
Interventions: Drug: Cisplatin
Drug: Etoposide
Drug: Placebo
Drug: ZD6474

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Arm A: ZD6474 Matched Placebo

Subjects will receive cisplatin 60 mg/m2 IV day 1 plus etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles plus ZD6474 matched placebo oral daily to be continued for the duration of the study. Prophylactic antiemetics will be given at the discretion of the treating investigator.

Cisplatin: Cisplatin 60 mg/m2 IV day 1 every 21 days for a total of 4 cycles

Etoposide: Etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles

Placebo: Matched placebo oral daily

Arm B: ZD6474

Subjects will receive cisplatin 60 mg/m2 IV day 1 plus etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles plus ZD6474 100mg oral daily to be continued for the duration of the study. Prophylactic antiemetics will be given at the discretion of the treating investigator.

Cisplatin: Cisplatin 60 mg/m2 IV day 1 every 21 days for a total of 4 cycles

Etoposide: Etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles

ZD6474: ZD6474 100mg oral daily to be continued for the duration of the study.

Safety Lead-In

Subjects will receive cisplatin 60 mg/m2 IV day 1 plus etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles plus ZD6474 100mg oral daily to be continued for the duration of the study. Prophylactic antiemetics will be given at the discretion of the treating investigator. The safety lead-in will be conducted to determine the safety of the combination of ZD6474 and cisplation + etopiside. If this combination is found to be unsafe, no patients will be randomized in the Phase II portion of the trial. If the combination is deemed safe according to the protocol, participants from the safety lead-in cohort will not be included in the efficacy analysis.

Cisplatin: Cisplatin 60 mg/m2 IV day 1 every 21 days for a total of 4 cycles

Etoposide: Etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles

ZD6474: ZD6474 100mg oral daily to be continued for the duration of the study.


Participant Flow:   Overall Study
    Arm A: ZD6474 Matched Placebo     Arm B: ZD6474     Safety Lead-In  
STARTED     33     34     7 [1]
1st Dose ZD6474     33     34     7  
COMPLETED     33     33     7  
NOT COMPLETED     0     1     0  
Ineligible                 0                 1                 0  
[1] These participants provided the toxicity data to determine if ZD6474+Etopiside+Cisplatin was safe.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Subjects 18 years of age or older at time of consent, ECOG Performance Status of 0-1 14 days prior to registration, and histological or cytological proof of chemotherapy naive extensive small cell cancers or neuroendocrine cancers that are high grade or poorly differentiated.

Reporting Groups
  Description
Arm A: ZD6474 Matched Placebo

Subjects will receive cisplatin 60 mg/m2 IV day 1 plus etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles plus ZD6474 matched placebo oral daily to be continued for the duration of the study. Prophylactic antiemetics will be given at the discretion of the treating investigator.

Cisplatin: Cisplatin 60 mg/m2 IV day 1 every 21 days for a total of 4 cycles

Etoposide: Etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles

Placebo: Matched placebo oral daily

Arm B: ZD6474

Subjects will receive cisplatin 60 mg/m2 IV day 1 plus etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles plus ZD6474 100mg oral daily to be continued for the duration of the study. Prophylactic antiemetics will be given at the discretion of the treating investigator.

Cisplatin: Cisplatin 60 mg/m2 IV day 1 every 21 days for a total of 4 cycles

Etoposide: Etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles

ZD6474: ZD6474 100mg oral daily to be continued for the duration of the study.

Safety Lead-In

Subjects will receive cisplatin 60 mg/m2 IV day 1 plus etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles plus ZD6474 100mg oral daily to be continued for the duration of the study. Prophylactic antiemetics will be given at the discretion of the treating investigator. The safety lead-in will be conducted to determine the safety of the combination of ZD6474 and cisplation + etopiside. If this combination is found to be unsafe, no patients will be randomized in the Phase II portion of the trial. If the combination is deemed safe according to the protocol, participants from the safety lead-in cohort will not be included in the efficacy analysis.

Cisplatin: Cisplatin 60 mg/m2 IV day 1 every 21 days for a total of 4 cycles

Etoposide: Etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles

ZD6474: ZD6474 100mg oral daily to be continued for the duration of the study.

Total Total of all reporting groups

Baseline Measures
    Arm A: ZD6474 Matched Placebo     Arm B: ZD6474     Safety Lead-In     Total  
Number of Participants  
[units: participants]
  33     33     7     73  
Age  
[units: years]
Mean (Standard Deviation)
  62.58  (10.92)     63.80  (5.90)     66.14  (3.34)     62.94  (8.83)  
Gender  
[units: participants]
       
Female     16     14     2     32  
Male     17     19     5     41  
Ethnicity (NIH/OMB)  
[units: participants]
       
Hispanic or Latino     0     0     0     0  
Not Hispanic or Latino     31     29     7     67  
Unknown or Not Reported     2     4     0     6  
Race (NIH/OMB)  
[units: participants]
       
American Indian or Alaska Native     0     0     0     0  
Asian     0     1     0     1  
Native Hawaiian or Other Pacific Islander     0     0     0     0  
Black or African American     1     1     2     4  
White     32     29     5     66  
More than one race     0     0     0     0  
Unknown or Not Reported     0     2     0     2  
Region of Enrollment  
[units: participants]
       
United States     33     33     7     73  
ECOG Performance Status [1]
[units: participants]
       
0     12     11     2     25  
1     21     22     5     48  
Liver Metastases  
[units: participants]
       
Present     16     13     1     30  
Absent     17     20     6     43  
Brain Metastases  
[units: participants]
       
Present     10     10     5     25  
Absent     23     23     2     48  
Platinum Therapy  
[units: participants]
       
Cisplatin     17     17     7     41  
Carboplatin     16     16     0     32  
[1]

Eastern Cooperative Oncology Group Score

0 Fully active, able to carry on all pre-disease performance without restriction

  1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
  2. Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours
  3. Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours
  4. Completely disabled; cannot carry on any selfcare; totally confined to bed or chair
  5. Dead



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Time to Disease Progression - Median Time to Progression and Log-Rank Test   [ Time Frame: 24 months ]

2.  Secondary:   Percentage of Participants With Grade 3/4 Hematologic and Non-Hematologic Toxicities   [ Time Frame: 6 weeks (2 Cycles) ]

3.  Secondary:   Measure the Response Rate (CR + PR) in Each Arm   [ Time Frame: 24 months ]

4.  Secondary:   Measure Disease Control Rate (CR + PR+ SD) in Each Arm   [ Time Frame: 24 months ]

5.  Secondary:   Measure Overall Survival for Each Arm   [ Time Frame: 24 months ]

6.  Secondary:   Assess VEGF Polymorphisms and Correlate Subject Response   [ Time Frame: 24 months ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The primary object analysis was under powered. The sample size calculation determined 34 subjects per arm, however the actual primary objective analysis was based on 31 subjects per arm.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Georgia Gould
Organization: Hoosier Cancer Research Network
phone: 317-921-2050
e-mail: ggould@hoosiercancer.org


Publications of Results:
Rachel E. Sanborn, Jyoti D. Patel, Gregory A. Masters, Nagesh Jayaram, Anthony W. Stephens, Michael J. Guarino, Jamal Ghazi Misleh, Corinne E. Williams, Jingwei Wu, Nasser H. Hanna. A randomized double-blind phase II trial of platinum (P) plus etoposide (E) with or without concurrent ZD6474 (Z) in patients (pts) with previously untreated extensive-stage (ES) small cell lung cancer (SCLC): Hoosier Oncology Group LUN06-113. J Clin Oncol 32:5s, 2014 (suppl; abstr 7506)


Responsible Party: Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT00613626     History of Changes
Other Study ID Numbers: LUN06-113
Study First Received: January 31, 2008
Results First Received: August 31, 2015
Last Updated: October 19, 2015
Health Authority: United States: Food and Drug Administration