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A Study for Patients With Head and Neck Cancer

This study has been completed.
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00415194
First received: December 20, 2006
Last updated: June 23, 2011
Last verified: June 2011
History of Changes
Results First Received: March 10, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Head and Neck Neoplasms
Interventions: Drug: pemetrexed
Drug: cisplatin
Drug: placebo

  Participant Flow
  Hide Participant Flow

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
Pemetrexed/Cisplatin

Pemetrexed 500 milligrams per meter square (mg/m^2) administered intravenously (IV) plus cisplatin 75 mg/m^2 IV on Day 1 every 21 days.

Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment.

Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose.

Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.
Placebo/Cisplatin

Placebo (approximately 100 mL normal saline) administered IV plus cisplatin 75 mg/m^2 on Day 1 every 21 days.

Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment.

Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose.

Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.

Participant Flow:   Overall Study
    Pemetrexed/Cisplatin     Placebo/Cisplatin  
STARTED     398     397  
Received at Least 1 Dose of Study Drug     392     385  
COMPLETED     70     55  
NOT COMPLETED     328     342  
Adverse Event                 37                 32  
Entry Criteria Not Met                 4                 8  
Lost to Follow-up                 1                 0  
Physician Decision                 10                 16  
Progressive Disease                 180                 217  
Protocol Violation                 4                 2  
Withdrawal by Subject                 28                 21  
Death Due to Study Disease                 26                 29  
Death Due to Study Drug Related AE                 11                 1  
Death Due to Procedural Related AE                 0                 1  
Death Due to AE (Other Causes)                 27                 15  



  Baseline Characteristics
  Hide Baseline Characteristics

Reporting Groups
  Description
Pemetrexed/Cisplatin

Pemetrexed 500 milligrams per meter square (mg/m^2) administered intravenously (IV) plus cisplatin 75 mg/m^2 IV on Day 1 every 21 days.

Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment.

Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose.

Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.
Placebo/Cisplatin

Placebo (approximately 100 mL normal saline) administered IV plus cisplatin 75 mg/m^2 on Day 1 every 21 days.

Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment.

Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose.

Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.
Total Total of all reporting groups

Baseline Measures
    Pemetrexed/Cisplatin     Placebo/Cisplatin     Total  
Number of Participants  
[units: participants]
 		  398     397     795  
Age  
[units: years]
Mean ± Standard Deviation 		  57.45  ± 9.54     57.78  ± 9.36     57.62  ± 9.44  
Gender  
[units: participants]
 		     
Female     56     53     109  
Male     342     344     686  
Race/Ethnicity, Customized  
[units: Participants]
 		     
African     17     12     29  
Caucasian     243     233     476  
East Asian     55     65     120  
Hispanic     11     16     27  
West Asian (Indian sub-continent)     72     70     142  
Unknown     0     1     1  
Region of Enrollment  
[units: participants]
 		     
Argentina     5     10     15  
Belgium     7     10     17  
Brazil     16     12     28  
China     5     7     12  
Denmark     7     3     10  
France     3     3     6  
Germany     50     48     98  
Hungary     23     22     45  
India     72     75     147  
Italy     19     21     40  
Korea, Republic of     29     24     53  
Mexico     9     8     17  
Netherlands     8     11     19  
Poland     10     10     20  
Romania     20     22     42  
Russian Federation     23     20     43  
South Africa     11     9     20  
Spain     31     29     60  
Taiwan     21     25     46  
United States     29     28     57  
Previously Treated for Head and Neck Cancer (HNC)  
[units: Participants]
 		     
No     35     39     74  
Yes     363     358     721  
Prior Treatment with Platinum-Based Therapy  
[units: Participants]
 		     
No     213     228     441  
Yes     185     169     354  
Distant Metastasis  
[units: Participants]
 		     
No     165     155     320  
Yes     233     242     475  
Eastern Cooperative Oncology Group (ECOG) Performance Status [1]
[units: Participants]
 		     
0     90     90     180  
1     257     253     510  
2     51     53     104  
Missing Data     0     1     1  
Primary Site of Disease  
[units: Participants]
 		     
Hypopharynx     63     59     122  
Larynx     103     102     205  
Oral Cavity     138     123     261  
Oropharynx     86     106     192  
Other     8     7     15  
[1]

These scales and criteria are used by doctors and researchers to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis:

  1. Fully active, able to carry on all pre-disease performance without restriction
  2. Restricted in strenuous activity,able to carry out work of a light or sedentary nature
  3. Ambulatory, but unable to carry out any work activities. Capable of only limited selfcare
  4. Completely disabled. Cannot carry on any selfcare.
  5. Dead



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Overall Survival (OS)   [ Time Frame: Baseline to date of death from any cause up to 36 months ]
  Show Outcome Measure 1

2.  Secondary:   Progression-free Survival (PFS)   [ Time Frame: baseline to measured progressive disease up to 33 months ]
  Hide Outcome Measure 2

Measure Type Secondary
Measure Title Progression-free Survival (PFS)
Measure Description Objective PFS is defined as the time from date of randomization to date of objectively determined progressive disease (PD) or death from any cause, whichever comes first. PD was defined by Response Evaluation Criteria in Solid Tumors (RECIST). PD=at least a 20% increase in sum of longest diameter of target lesions. For participants who are not known to have died as of the data-inclusion cut-off date, and who do not have progressive disease, PFS will be censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systemic anticancer therapy.
Time Frame baseline to measured progressive disease up to 33 months  
Safety Issue No  

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.
Intention to Treat (ITT) Population - defines the treatment group as those to which participants were assigned by random allocation, even if a participant did not take the assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol.

Reporting Groups
  Description
Pemetrexed/Cisplatin

Pemetrexed 500 milligrams per meter square (mg/m^2) administered intravenously (IV) plus cisplatin 75 mg/m^2 IV on Day 1 every 21 days.

Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment.

Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose.

Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.
Placebo/Cisplatin

Placebo (approximately 100 mL normal saline) administered IV plus cisplatin 75 mg/m^2 on Day 1 every 21 days.

Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment.

Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose.

Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose.

Measured Values
    Pemetrexed/Cisplatin     Placebo/Cisplatin  
Number of Participants Analyzed  
[units: participants]
 		  398     397  
Progression-free Survival (PFS)  
[units: months]
Median ( 95% Confidence Interval ) 		  3.61  
  ( 3.15 to 4.07 )   		  2.79  
  ( 2.69 to 3.22 )  


Statistical Analysis 1 for Progression-free Survival (PFS)
Groups [1] All groups
Method [2] Stratified Log Rank
P Value [3] 0.166
Hazard Ratio (HR) [4] 0.88
95% Confidence Interval ( 0.76 to 1.03 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



3.  Secondary:   Percent of Participants With a Tumor Response (Response Rate)   [ Time Frame: Baseline to progressive disease or discontinuation of study treatment up to 11 months ]
  Show Outcome Measure 3

4.  Secondary:   Duration of Response (DoR)   [ Time Frame: time of response to progressive disease up to 24 months ]
  Show Outcome Measure 4

5.  Secondary:   Time to Treatment Worsening in Functional Assessment of Cancer Therapy - Head and Neck Cancer (FACT-H&N) Total Score   [ Time Frame: Baseline (</=Day 1 of first dose) and Day 1 of every subsequent cycle to 30-day post-study completion up to 33 months ]
  Show Outcome Measure 5

6.  Secondary:   Correlation Between Biomarkers and Treatment Effect   [ Time Frame: Baseline ]
  Show Outcome Measure 6


  Serious Adverse Events
  Show Serious Adverse Events


  Other Adverse Events
  Show Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Limitations and Caveats
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
No text entered.  


Results Point of Contact:  
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 800-545-5979


No publications provided


Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00415194     History of Changes
Other Study ID Numbers: 8431, H3E-MC-JMHR
Study First Received: December 20, 2006
Results First Received: March 10, 2011
Last Updated: June 23, 2011
Health Authority: United States: Food and Drug Administration