A Study in Head and Neck Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01081041
First received: March 3, 2010
Last updated: June 12, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Drug: Cetuximab
Drug: Cisplatin
Drug: Carboplatin
Drug: 5-Fluorouracil
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Parts 1 and 2: Randomization to date of death from any cause ] [ Designated as safety issue: No ]
    OS was the duration from randomization to death from any cause. For participants who were alive, OS was censored at the last contact.

  • Progression-Free Survival (PFS) [ Time Frame: Parts 1 and 2: Randomization to the first date of objective progression of disease or death from any cause ] [ Designated as safety issue: No ]
    PFS was defined as the time from randomization to the first observation of disease progression or death due to any cause. For participants who were alive or whose disease status was unknown were censored at last complete tumor assessment.

  • Percentage of Participants Having a Confirmed Best Response of Complete Response (CR) or Partial Response (PR) [ Time Frame: Parts 1 and 2: Randomization to progression of disease ] [ Designated as safety issue: No ]
    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.

  • Anti-Cetuximab Antibodies [ Time Frame: Parts 1 and 2: Day 1 of Week 1 in Cycles 1, 3, and 5, and 30 days post treatment discontinuation ] [ Designated as safety issue: No ]
  • Percentage of Participants Having a Best Response of CR, PR, or Stable Disease (SD) [ Time Frame: Parts 1 and 2: Randomization to progression of disease ] [ Designated as safety issue: No ]
    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. Percentage of participants with a confirmed CR, PR, or SD=(number of participants whose best overall response was CR, PR, or SD)/(number of participants treated)*100.

  • Maximum Serum Concentration (Cmax) of Cetuximab Following 400 mg/m^2 Cetuximab Dosing [ Time Frame: Part 2: Cycle 1, Day 1: 0 hours [(h); immediately postdose], 1 h, 2 h, and 24 h postdose ] [ Designated as safety issue: No ]
    The Cmax of cetuximab following 400 mg/m^2 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.

  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 187
Study Start Date: July 2010
Estimated Study Completion Date: September 2014
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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: 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.

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: 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.

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01081041

  Show 26 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01081041     History of Changes
Other Study ID Numbers: 13611, I4E-MC-JXBD
Study First Received: March 3, 2010
Results First Received: June 12, 2014
Last Updated: June 12, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Mexico: Ethics Committee
Mexico: Ministry of Health

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Cetuximab
Cisplatin
Carboplatin
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 16, 2014