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A Study in Head and Neck Cancer

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01081041
First Posted: March 5, 2010
Last Update Posted: April 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Eli Lilly and Company
March 3, 2010
March 5, 2010
June 12, 2014
July 14, 2014
April 12, 2017
June 2010
August 2013   (Final data collection date for primary outcome measure)
  • Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs); Data Analysis Cut-Off: September 27, 2013 [ Time Frame: Part 2: Baseline to end of combination therapy (up to 18 weeks) ]
    September 27, 2013 is the date when data was last collected for the primary endpoint. Prior to this date, the manufacturing process for the BI-manufactured cetuximab was changed necessitating the need to switch participants to US commercial cetuximab. All other components of their treatment regimen remained unchanged and participants stayed in their original reporting group. Therefore, the number of participants in the BI-manufactured cetuximab treatment arm who had TEAEs includes TEAEs while participants received BI-manufactured and US-commercial cetuximab. Using September 27 cut-off, the analysis of TEAEs is confounded by the switch from BI-manufactured to US commercial cetuximab. TEAEs were defined as serious and other non-serious AEs that occurred or worsened after study treatment (regardless of causality). TEAE information for Safety Lead-In group available in Reported Adverse Events module which is summary of serious and other non-serious AEs regardless of causality.
  • Number of Participants Who Had TEAEs; Data Analysis Cut-Off: January 23, 2013 [ Time Frame: Part 2: Baseline to end of combination therapy or date first participant switched to US commercial cetuximab (up to 18 weeks) ]
    January 23, 2013 is the date when the first participant in the BI-manufactured cetuximab treatment arm switched to US commercial cetuximab due to changes in the manufacturing process for the BI-manufactured cetuximab necessitating the need to switch participants to US commercial cetuximab. Each participant who switched treatments received at least 2 cycles of BI-manufactured cetuximab before switching. All other components of their treatment regimen remained unchanged. The number of participants who had TEAEs during combination therapy is reported. Using January 23 cut-off, data is un-confounded by lack of BI-manufactured cetuximab. TEAEs were defined as serious and other non-serious adverse events (AEs) that occurred or worsened after study treatment (regardless of causality). TEAE information for Safety Lead-in group available in Reported Adverse Event module which is summary of serious and other non-serious AEs regardless of causality.
Incidence of treatment emergent adverse events [ Time Frame: Randomization to 30 days after treatment discontinuation ]
Complete list of historical versions of study NCT01081041 on ClinicalTrials.gov Archive Site
  • Overall Survival (OS) [ Time Frame: Parts 1 and 2: Randomization to Date of Death from any Cause (Up to 36.3 Months) ]
    OS was defined as duration from the date of randomization to the date of death from any cause. For each participant not known to have died as of the 23 October 2014 data cutoff date for the analysis, OS was censored at the date last known to be alive. In addition, any participants on Arm B who was switched from BI-manufactured cetuximab to ImClone-manufactured cetuximab was censored at the time of the switch.
  • Progression-Free Survival (PFS) [ Time Frame: Parts 1 and 2: Randomization to Progression of Disease or Death from any Cause (Up to 32.7 Months) ]
    PFS was defined as duration from the date of randomization to the first date of objective progressive disease (PD) or death from any cause. For each participant who was not known to have died or to have had objective PD as of the 23 October 2014 data cutoff date for the analysis, PFS was censored at the date of the participant's last complete tumor assessment prior to that cutoff date. In addition, any participant in Arm B who was switched from BI-manufactured cetuximab to ImClone-manufactured cetuximab was censored at the time of the switch.
  • Percentage of Participants Having a Confirmed Best Response of Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) [ Time Frame: Parts 1 and 2: Randomization to Progression of Disease (Up to 32.7 Months) ]
    Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version [v]1.0) criteria. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. Percentage of participants with a confirmed CR or PR=(number of participants whose best overall response was CR or PR)/(number of participants treated)*100.
  • Number of Participants With Anti-Cetuximab Antibodies [ Time Frame: Day 1, Week 1 of Cycles 3 and 5 (postbaseline samples were collected prior to infusion). ]
  • Percentage of Participants Having a Best Response of CR, PR, or Stable Disease (SD) - Disease Control Rate (DCR) [ Time Frame: Parts 1 and 2: Randomization to Progression of Disease (Up to 32.7 Months) ]
    Response was defined using RECIST, v1.0 criteria. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. Progressive Disease (PD) was defined as having at least a 20% increase in the sum of the longest diameter of target lesions. Stable Disease (SD) was defined as small changes that did not meet the above criteria.
  • Maximum Serum Concentration (Cmax) of Cetuximab Following 400 mg/m² Cetuximab Dosing [ Time Frame: Part 2: Cycle 1, Day 1: 0 hours [(h); immediately postdose], 1 h, 2 h, and 24 h postdose ]
    The Cmax of cetuximab following 400 mg/m² cetuximab dosing during Part 2 of the study is reported. As specified in the protocol, pharmacokinetics (PK) samples were not collected during Part 1 of the study, Safety Lead-In or during Part 2 monotherapy.
  • Cmax of Cetuximab at Steady State [ Time Frame: Part 2: Weekly from Cycle 1, Week 3 through Cycle 3, Week 3: 0 h (immediately postdose), 24 h, 96 h, and 168 h postdose ]
    A total of 4 samples were collected at various times during combination therapy, from the third dose of 250 mg/m^2 cetuximab in Cycle 1 (Week 3) through the final dose in Cycle 3 (Week 3) and used to report Cmax of cetuximab at steady state during Part 2 of the study. As specified in the protocol, PK samples were not collected during Part 1 of the study, Safety Lead-In, or during Part 2 monotherapy.
  • Area Under the Concentration Curve (AUC) of Cetuximab at Steady State [ Time Frame: Part 2: Weekly from Cycle 1, Day 1 through Cycle 3, Week 3: 0 h (immediately postdose), 24 h, 96 h, and 168 h postdose ]
    A total of 4 samples were collected during combination therapy, from the first dose of 250 mg/m^2 cetuximab in Cycle 1 (Day 1) through the final dose in Cycle 3 (Week 3) and used to report AUC of cetuximab at steady state during Part 2 of the study. As specified in the protocol, PK samples were not collected during Part 1 of the study, Safety Lead-In, or during Part 2 monotherapy.
  • Overall Survival (OS) [ Time Frame: Randomization to date of death from any cause ]
  • Progression-Free Survival (PFS) [ Time Frame: Randomization to the first date of objective progression of disease or death from any cause ]
  • Proportion of patients having a confirmed best response of Partial Response (PR) or Complete Response (CR) [ Time Frame: Randomization to progression of disease ]
  • Plasma concentration of Cetuximab [ Time Frame: Cycle 1, week 1: 0 (immediately after), 1, 2 and 24 h (post-doses). Any 4 doses between Cycle 1, week 3 and Cycle 3 week 3: 0 (immediately after), 24, 96 and 168 h (post-doses) ]
  • Anti-Cetuximab Antibodies [ Time Frame: Day 1 of Week 1 in Cycles 1, 3, and 5, and at the 30-day follow-up visit after the end of treatment ]
  • Proportion of patients having a confirmed best response of PR or CR, or best response of stable disease (SD) [ Time Frame: Randomization to progression of disease ]
  • Cmax of Cetuximab [ Time Frame: Cycle 1, week 1: 0 (immediately after), 1, 2 and 24 h (post-doses). Any 4 doses between Cycle 1, week 3 and Cycle 3 week 3: 0 (immediately after), 24, 96 and 168 h (post-doses) ]
  • AUC of Cetuximab [ Time Frame: Cycle 1, week 1: 0 (immediately after), 1, 2 and 24 h (post-doses). Any 4 doses between Cycle 1, week 3 and Cycle 3 week 3: 0 (immediately after), 24, 96 and 168 h (post-doses) ]
Not Provided
Not Provided
 
A Study in Head and Neck Cancer
A Randomized, Double-Blind, Phase 2 Safety Study of Cetuximab, Using ImClone Versus Boehringer Ingelheim Manufacturing Processes, in Combination With Cisplatin or Carboplatin and 5-Fluorouracil in the First-Line Treatment of Patients With Locoregionally Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck

This study will begin with a 30 participant lead-in part: these 30 participants will receive cetuximab manufactured by ImClone on a weekly basis in combination with other chemotherapy drugs [cisplatin or carboplatin plus 5-fluorouracil (5-FU)] administered every 3 weeks. After 18 weeks, participants who benefit from this treatment may continue to receive cetuximab once-weekly until progression of the disease, an unacceptable side effect occurs, participants withdraw consent, or the study is closed.

In the second part of this study, 200 participants will be randomized in 2 arms:

  • 100 participants will receive commercial cetuximab manufactured by ImClone (Group A)
  • 100 participants will receive cetuximab manufactured by Boehringer Ingelheim (Group B).

All these 200 participants will receive other chemotherapy drugs (cisplatin or carboplatin plus 5-FU) administered every 3 weeks. After 18 weeks, participants who benefit from this treatment may continue to receive cetuximab once-weekly until progression of the disease, an unacceptable side effect occurs, participants withdraw consent, or the study is closed.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Head and Neck Cancer
  • Drug: Cetuximab
    Administered intravenously
    Other Names:
    • Erbitux
    • LY2939777
  • Drug: Cisplatin
    Administered intravenously
  • Drug: Carboplatin
    Administered intravenously
  • Drug: 5-Fluorouracil
    Administered intravenously
    Other Name: 5-FU
  • Experimental: Safety Lead-In (cetuximab manufactured by ImClone)

    Cycle 1:

    Week 1 - Cetuximab 400 milligrams per square meter (mg/m^2) on Day 1; Cisplatin 100 mg/m^2 on Day 1 or carboplatin area under the curve (AUC) 5 on Day 1; 5-FU 1000 mg/m^2 on Days 1-4

    Week 2 - Cetuximab 250 mg/m^2 on Day 1

    Week 3 - Cetuximab 250 mg/m^2 on Day 1

    Cycle 2-6:

    Week 1 - Cetuximab 250 mg/m^2 on Day 1; Cisplatin 100 mg/m^2 on Day 1 or carboplatin AUC 5 on Day 1; 5-FU 1000 mg/m^2 on Days 1-4

    Week 2 - Cetuximab 250 mg/m^2 on Day 1

    Week 3 - Cetuximab 250 mg/m^2 on Day 1

    After 6 cycles, participants may then receive weekly cetuximab monotherapy 250 mg/m^2 until progression of disease, unacceptable toxicity, or another withdrawal criteria is met.

    Interventions:
    • Drug: Cetuximab
    • Drug: Cisplatin
    • Drug: Carboplatin
    • Drug: 5-Fluorouracil
  • Experimental: Cetuximab manufactured by ImClone

    Cycle 1:

    Week 1 - Cetuximab 400 mg/m^2 on Day 1; Cisplatin 100 mg/m^2 on Day 1 or carboplatin AUC 5 on Day 1; 5-FU 1000 mg/m^2 on Days 1-4

    Week 2 - Cetuximab 250 mg/m^2 on Day 1

    Week 3 - Cetuximab 250 mg/m^2 on Day 1

    Cycle 2-6:

    Week 1 - Cetuximab 250 mg/m^2 on Day 1; Cisplatin 100 mg/m^2 on Day 1 or carboplatin AUC 5 on Day 1; 5-FU 1000 mg/m^2 on Days 1-4

    Week 2 - Cetuximab 250 mg/m^2 on Day 1

    Week 3 - Cetuximab 250 mg/m^2 on Day 1

    After 6 cycles, participants may then receive weekly cetuximab monotherapy 250 mg/m^2 until progression of disease, unacceptable toxicity, or another withdrawal criteria is met.

    Interventions:
    • Drug: Cetuximab
    • Drug: Cisplatin
    • Drug: Carboplatin
    • Drug: 5-Fluorouracil
  • Experimental: Cetuximab manufactured by Boehringer Ingelheim

    Cycle 1:

    Week 1 - Cetuximab 400 mg/m^2 on Day 1; Cisplatin 100 mg/m^2 on Day 1 or carboplatin AUC 5 on Day 1; 5-FU 1000 mg/m^2 on Days 1-4

    Week 2 - Cetuximab 250 mg/m^2 on Day 1

    Week 3 - Cetuximab 250 mg/m^2 on Day 1

    Cycle 2-6:

    Week 1 - Cetuximab 250 mg/m^2 on Day 1; Cisplatin 100 mg/m^2 on Day 1 or carboplatin AUC 5 on Day 1; 5-FU 1000 mg/m^2 on Days 1-4

    Week 2 - Cetuximab 250 mg/m^2 on Day 1

    Week 3 - Cetuximab 250 mg/m^2 on Day 1

    After 6 cycles, participants may then receive weekly cetuximab monotherapy 250 mg/m^2 until progression of disease, unacceptable toxicity, or another withdrawal criteria is met.

    Interventions:
    • Drug: Cetuximab
    • Drug: Cisplatin
    • Drug: Carboplatin
    • Drug: 5-Fluorouracil
Soulières D, Aguilar JL, Chen E, Misiukiewicz K, Ernst S, Lee HJ, Bryant K, He S, Obasaju CK, Chang SC, Chin S, Adkins D. Cetuximab plus platinum-based chemotherapy in head and neck squamous cell carcinoma: a randomized, double-blind safety study comparing cetuximab produced from two manufacturing processes using the EXTREME study regimen. BMC Cancer. 2016 Jan 14;16:19. doi: 10.1186/s12885-016-2064-0.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
187
September 2015
August 2013   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Head and neck cancer that was confirmed by tissue biopsy or cytology
  • Disease not suitable for local therapy
  • Measurable or evaluable disease
  • Karnofsky performance status (KPS) score of at least 70
  • Organs are functioning well (bone marrow reserve, liver and kidney)
  • Life expectancy of at least 12 weeks
  • Signed informed consent document

Exclusion Criteria:

  • Receiving another investigational medication within the last 30 days
  • Prior chemotherapy, except if given as part of a multimodal treatment for locally advanced head and neck cancer that was completed more than 4 months prior to study entry.
  • Nasopharyngeal carcinoma
  • Previous treatment with monoclonal antibody therapy or other signal transduction inhibitors or epidermal growth factor receptor (EGFR) targeting therapy except for prior cetuximab treatment given as part of a multimodal treatment for locally advanced head and neck cancer that was completed more than 4 months prior to study entry.
  • Uncontrolled high blood pressure
  • Heart disease or had a heart attack within the last year
  • Currently have an infection that requires for you to take an IV antibiotic
  • Currently receiving other therapies for your cancer, such as chemotherapy, radiation therapy, immunotherapy, and hormonal therapy
  • Medical or psychological condition that would not permit the participant to complete the study or sign informed consent
  • Known drug abuse (with the exception of alcohol abuse)
  • Known allergic reaction against any of the components of the study treatment
  • Second primary malignancy that is clinically detectable at the time of consideration for study enrollment
  • Have had another type of cancer within the last 2 years
  • You are currently pregnant or breastfeeding
  • You are considering becoming pregnant or fathering a child
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Canada,   Mexico,   United States
 
 
NCT01081041
13611
I4E-MC-JXBD ( Other Identifier: Eli Lilly and Company )
No
Not Provided
Plan to Share IPD: Yes
Plan Description:

Lilly provides access to the individual patient data from studies on approved medicines and indications as defined by the sponsor specific information on ClinicalStudyDataRequest.com.

This access is provided in a timely fashion after the primary publication is accepted. Researchers need to have an approved research proposal submitted through ClinicalStudyDataRequest.com. Access to the data will be provided in a secure data sharing environment after signing a data sharing agreement.

Eli Lilly and Company
Eli Lilly and Company
Not Provided
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
Eli Lilly and Company
March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP