Head and Neck CancerPhase 2NCT01081041
A Study in Head and Neck Cancer
A Phase 2 study testing Cetuximab, Cisplatin and Carboplatin in people with Head and Neck Cancer, run by Eli Lilly and Company at 26 sites in 3 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer
- What is being tested?
- Cetuximab, Cisplatin and Carboplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 187 participants
- Where
- 26 sitesin 3 countries
- Study dates
- Jun 2010to Sep 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
26 sites in 3 countries.
26 sites in 3 countries
United States15 sites
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Abilene, Texas, 79606
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Albany, Georgia, 31701
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Albany, New York, 12208
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Charleston, South Carolina, 29425
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Chicago, Illinois, 60612
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Fullerton, California, 92835
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Grand Junction, Colorado, 81501
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Long Beach, California, 90813
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
New Albany, Indiana, 47150
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
New York, New York, 10029
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Portland, Oregon, 97207
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Springfield, Illinois, 62703
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Tucson, Arizona, 85715
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Weston, Florida, 33331
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Wichita, Kansas, 67214
Canada6 sites
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Calgary, Alberta, T2N 4N2
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Edmonton, Alberta, T6G 1Z2
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
London, Ontario, N6A 4L6
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Montreal, Quebec, H2L 4M1
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Ottawa, Ontario, K1H 8L6
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Toronto, Ontario, M5G 2M9
Mexico5 sites
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Chihuahua City, 31000
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Guadalajara, 44200
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Mérida, 97000
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Mexico City, 14000
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Monterrey, 64320
About this study
Official title: 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:
Read more
- 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.
- Conditions
- Head and Neck Cancer
- Being tested
- Cetuximab, Cisplatin, Carboplatin, 5-Fluorouracil
- Medical subject headings
- Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CetuximabDrug
Also called Erbitux, LY2939777
Administered intravenously
CisplatinDrug
Administered intravenously
CarboplatinDrug
Administered intravenously
5-FluorouracilDrug
Also called 5-FU
Administered intravenously
| Study group | Role | What they receive |
|---|---|---|
| Safety Lead-In (cetuximab manufactured by ImClone) | Experimental | 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. Receives: Drug: Cetuximab; Drug: Cisplatin; Drug: Carboplatin; Drug: 5-Fluorouracil |
| Cetuximab manufactured by ImClone | Experimental | 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. Receives: Drug: Cetuximab; Drug: Cisplatin; Drug: Carboplatin; Drug: 5-Fluorouracil |
| Cetuximab manufactured by Boehringer Ingelheim | Experimental | 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. Receives: Drug: Cetuximab; Drug: Cisplatin; Drug: Carboplatin; Drug: 5-Fluorouracil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs); Data Analysis Cut-Off: September 27, 2013
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.
Measured: Part 2: Baseline to end of combination therapy (up to 18 weeks)
Number of Participants Who Had TEAEs; Data Analysis Cut-Off: January 23, 2013
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.
Measured: Part 2: Baseline to end of combination therapy or date first participant switched to US commercial cetuximab (up to 18 weeks)
Secondary outcomes (8)
Overall Survival (OS)
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.
Measured: Parts 1 and 2: Randomization to Date of Death from any Cause (Up to 36.3 Months)
Progression-Free Survival (PFS)
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.
Measured: Parts 1 and 2: Randomization to Progression of Disease or Death from any Cause (Up to 32.7 Months)
Percentage of Participants Having a Confirmed Best Response of Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])
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.
Measured: Parts 1 and 2: Randomization to Progression of Disease (Up to 32.7 Months)
Number of Participants With Anti-Cetuximab Antibodies
Measured: 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)
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.
Measured: Parts 1 and 2: Randomization to Progression of Disease (Up to 32.7 Months)
Maximum Serum Concentration (Cmax) of Cetuximab Following 400 mg/m² Cetuximab Dosing
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.
Measured: Part 2: Cycle 1, Day 1: 0 hours [(h); immediately postdose], 1 h, 2 h, and 24 h postdose
Cmax of Cetuximab at Steady State
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.
Measured: 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
Area Under the Concentration Curve (AUC) of Cetuximab at Steady State
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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2010 (estimated)
- Study startJun 2010
- Primary completionAug 2013
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 187 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01081041
- Sponsor's protocol ID
- 13611
- Other IDs
- I4E-MC-JXBD
- Status last verified
- Sep 2019
- First submitted
- 3 Mar 2010
- Last updated
- 25 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Publications
Soulieres 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.
PubMed 26768732
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01081041
- Acronym / sponsor ID
- 13611
- Conditions
- Head and Neck Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 187 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- Jun 2010
- Primary completion
- Aug 2013 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 5 Mar 2010 (estimated)
- Results
- Posted 14 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Safety Lead-In (cetuximab manufactured by ImClone) | Experimental | Drug: Cetuximab, Drug: Cisplatin, Drug: Carboplatin, Drug: 5-FluorouracilCycle 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. |
| Cetuximab manufactured by ImClone | Experimental | Drug: Cetuximab, Drug: Cisplatin, Drug: Carboplatin, Drug: 5-FluorouracilCycle 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. |
| Cetuximab manufactured by Boehringer Ingelheim | Experimental | Drug: Cetuximab, Drug: Cisplatin, Drug: Carboplatin, Drug: 5-FluorouracilCycle 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CetuximabAlso: Erbitux, LY2939777Administered intravenously | Drug | Cetuximab manufactured by Boehringer Ingelheim, Cetuximab manufactured by ImClone, Safety Lead-In (cetuximab manufactured by ImClone) |
| CisplatinAdministered intravenously | Drug | Cetuximab manufactured by Boehringer Ingelheim, Cetuximab manufactured by ImClone, Safety Lead-In (cetuximab manufactured by ImClone) |
| CarboplatinAdministered intravenously | Drug | Cetuximab manufactured by Boehringer Ingelheim, Cetuximab manufactured by ImClone, Safety Lead-In (cetuximab manufactured by ImClone) |
| 5-FluorouracilAlso: 5-FUAdministered intravenously | Drug | Cetuximab manufactured by Boehringer Ingelheim, Cetuximab manufactured by ImClone, Safety Lead-In (cetuximab manufactured by ImClone) |
Primary outcome
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.
8 secondary outcomes
Overall Survival (OS)
Time frame: Parts 1 and 2: Randomization to Date of Death from any Cause (Up to 36.3 Months)
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)
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)
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)
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26768732Soulieres 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.
- Individual participant dataSharing planned: Yes. Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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) study director
Eli Lilly and Company
26 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cetuximab, Cisplatin and Carboplatin in people with Head and Neck Cancer, run by Eli Lilly and Company at 26 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in United States, Canada, Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01081041, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2019.