A Study for Patients With Recurrent or Metastatic Squamous Cell Head and Neck Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01057589
First received: January 20, 2010
Last updated: September 5, 2013
Last verified: September 2013
  Purpose

The purpose of this trial is to estimate progression free survival in patients with recurrent or metastatic head and neck cancer that have not received chemotherapy in this setting.


Condition Intervention Phase
Head and Neck Neoplasms
Drug: Pemetrexed
Drug: Cetuximab
Drug: Cisplatin
Dietary Supplement: Folic Acid
Dietary Supplement: Vitamin B12
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Study of Pemetrexed in Combination With Cisplatin and Cetuximab in Recurrent 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:
  • Progression Free Survival (PFS) [ Time Frame: Baseline to date of PD or death up to 18.7 months ] [ Designated as safety issue: No ]
    PFS based on Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines defined as the time from the date of first dose of study drug to first documented objective progressive disease (PD) or death from any cause. PD is defined as at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Baseline to date of death up to 18.7 months ] [ Designated as safety issue: No ]
    OS defined as the time from the date of first dose of study drug to the date to death from any cause.

  • Percent of Participants With a Partial Response (PR) or a Complete Response (CR) [ Time Frame: Date of first response to PD (up to 18.7 months) ] [ Designated as safety issue: No ]
    CR and PR based on RECIST Guidelines: CR is defined as the disappearance of all tumor lesions; PR is defined as at least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LDs or the complete disappearance of target lesions, with persistence (but not worsening) of one or more nontarget lesions and the appearance of no new lesions. PD is defined as at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

  • Change From Baseline in Participant Reported European-Quality of Life 5 Dimension Instrument (EQ-5D) Visual Analog Scale (VAS) at End of Triplet Combination Therapy and End of Maintenance Therapy [ Time Frame: Baseline, End of Triplet Combination Therapy (up to Cycle 6 [4.2 months]), End of Maintenance Therapy (up to 18.7 months) ] [ Designated as safety issue: No ]
    Vertical VAS - a 20 millimeter (mm), fractionated scale in the form of a thermometer with endpoints of 0 (worst imaginable health state) and 100 (best imaginable health state). Participants used the EQ-5D VAS scale to rate their overall health on the day the questionnaire was administered. Possible change values range from -100 (best imaginable health at baseline changed to worst possible health at visit) to 100 (worst possible health at baseline changed to best possible health at visit).

  • Change From Baseline in Participant Reported EQ-5D Utility Score at End of Triplet Combination Therapy and End of Maintenance Therapy [ Time Frame: Baseline, End of Triplet Combination Therapy (up to 6 cycles [4.2 months]) , End of Maintenance Therapy (up to 18.7 months) ] [ Designated as safety issue: No ]
    EQ-5D Index is derived by converting the Descriptive System (participant is required to rate health by checking 1 [no limitation], 2 [some limitation] or 3 [severe or complete limitation] in 5 dimensions [mobility, self-care, usual activities, pain/comfort and anxiety/depression]) to a single summary index. A utility value assigned to each individual's health state based on the absence or presence of moderate or severe problems in the 5 dimensions. A regression equation defines a utility value for these health states. The possible values for health utility ranged from -0.59 (severe problems in all 5 dimensions) to 1 (no problem in all dimensions) on a scale where 0 represents death and 1 represents the best possible health state. Possible change values range from -1.59 (no problems at baseline to severe problems at visit) to 1.59 (severe problems at baseline to no problems at visit).

  • Change From Baseline in Performance Status Scale for Head and Neck Cancer Patients (PSS-HNC) [ Time Frame: Baseline, Triplet Combination Therapy Cycles 2, 4, 6 (cycle = 21 days) and optional Maintenance Therapy Cycles 1, 3, 5 and 7 (cycle = 21 days) ] [ Designated as safety issue: No ]
    PSS-HNC is a clinician-rated instrument designed to measure speaking and eating disabilities of participants with head and neck cancer and consists of 3 subscales: Normalcy of Diet (NOD) subscale measures the ability of the participants to eat a normal diet, scale ranged from 0 (non-oral feeding) to 100 (unrestricted diet); Understandability of Speech (UOS)subscale measured the degree a clinician was able to understand the participant's speech, subscale ranged from 0 (never understandable) to 100 (always understandable); Eating in Public (EIP) subscale, rating based on clinician question to the participant to report who he/she eats with and in what setting, subscale ranged from 0 (always eats alone) to 100 (no restriction of place, food, or companion). Change from baseline: negative value represents a decrease in function and a positive value represents an increase in function.


Enrollment: 66
Study Start Date: February 2010
Study Completion Date: October 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pemetrexed + Cisplatin + Cetuximab

Participants will receive pemetrexed,cisplatin and cetuximab for up to 6 cycles (21 days per cycle) followed by optional maintenance of pemetrexed and cetuximab until disease progression. Optional maintenance therapy is permitted after at least 4 cycles of triplet combination therapy have been given. Cetuximab will be administered as an initial dose of 400 milligram per meter squared (mg/m^2) intravenous (IV) infusion and as a 250 mg/m^2 IV weekly dose thereafter.

As Standard of care dietary supplements included: 350 to 1000 micrograms (µg) oral Folic Acid 5 times a day for the 7 days preceding the first dose of first dose of pemetrexed and continuing throughout treatment and for 21 days after the last dose of pemetrexed and 1000 µg vitamin B12 intramuscular injection (IM) during the week preceding the first dose of pemetrexed and every 9 weeks thereafter.

Drug: Pemetrexed

Triplet Combination Therapy: 500 mg/m^2 administered intravenously on Day 1 of 21 day cycle for up to 6 cycles

Maintenance Therapy: 500mg/m^2 administered intravenously on Day 1 of 21 day cycle until disease progression or unacceptable toxicity

Other Names:
  • Alimta
  • LY231514
Drug: Cetuximab

Triplet Combination Therapy: 400 mg/m^2 administered intravenously on Day 1 of 21 day cycle for 1 cycle; 250 mg/m^2 administered IV infusion on Day 1 of 21 day cycle and then weekly for up to 6 cycles.

Maintenance Therapy: 250 mg/m^2 administered intravenously on Day 1 of 21 day cycle and then weekly until disease progression or unacceptable toxicity

Drug: Cisplatin
Triplet Combination Therapy: 75mg/m^2 administered intravenously on Day 1 of 21 day cycle for up to 6 cycles.
Dietary Supplement: Folic Acid
Standard of care dietary supplements: 350 to 1000 µg orally 5 times a day for the 7 days preceding the first dose of first dose of pemetrexed and continuing throughout treatment and for 21 days after the last dose of pemetrexed.
Dietary Supplement: Vitamin B12
Standard of care dietary supplements: 1000 µg IM during the week preceding the first dose of pemetrexed and every 9 weeks thereafter.

Detailed Description:

A 12 patient safety lead will evaluate side effects in patients receiving at least 2 cycles of the combination pemetrexed, cisplatin and cetuximab.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed diagnosis of squamous cell carcinoma of head and neck (SCCHN)
  • Recurrent or metastatic SCCHN, not amenable to local therapy
  • At least 6 months since completion of systemic therapy (chemotherapy or biological anticancer therapy)
  • No more than 1 prior systemic therapy, given as part of multimodal treatment for locally advanced disease;
  • No prior systemic therapy for metastatic disease
  • Radiation therapy must be completed at least 4 weeks before study enrollment.
  • For palliative therapy, prior radiation therapy allowed to <25% of the bone marrow (Cristy and Eckerman 1987), and prior radiation to the whole pelvis is not allowed.
  • Surgery (excluding prior diagnostic biopsy) must be completed at least 4 weeks before study enrollment.
  • An estimated life expectancy of at least 12 weeks.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Oken et al. 1982).
  • Biological tissue available for biomarker analysis on tumor tissue.
  • Disease status may be measurable or nonmeasurable as defined by Response Evaluation Criteria in Solid Tumors
  • Patient compliance and geographic proximity that allow for adequate follow-up.
  • Adequate organ function
  • Willingness to comply with Contraceptive Regimen
  • For women: Must be surgically sterile, postmenopausal, or compliant with a medically approved contraceptive regimen [for example, intrauterine device (IUD), birth control pills, or barrier device] during and for 6 months after the treatment period; must have a negative serum or urine pregnancy test within 7 days before study enrollment, and must not be breast-feeding. For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 6 months after the treatment period.

Exclusion Criteria:

  • Nasopharyngeal, paranasal sinus, lip, or salivary gland cancer.
  • Previously received treatment with monoclonal antibody therapy, or other signal transduction inhibitors of Epidermal Growth Factor Receptor therapy.
  • Are receiving concurrent chronic systemic immune therapy, or chemotherapy for a disease other than cancer.
  • Serious concomitant systemic disorder (for example, active infection) or psychiatric disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study.
  • Have serious cardiac disease, such as symptomatic , unstable angina, or the history of myocardial infarction in the previous 12 months.
  • Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
  • Have had another primary malignancy other than Head and Neck cancer, unless that prior malignancy was treated at least 2 years previously with no evidence of recurrence. Exception: Patients with a history of in situ carcinoma of the cervix, nonmelanoma skin cancer, or low-grade (Gleason score less than or equal to 6) localized prostate cancer will be eligible even if diagnosed and treated less than 2 years previously.
  • Presence of clinically significant (by physical exam) third-space fluid collections; for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study entry.
  • Have peripheral neuropathy
  • Have central nervous system (CNS) metastases (unless the patient has completed successful local therapy for CNS metastases and has been off corticosteroids for at least 4 weeks before starting study therapy). Brain imaging is required in symptomatic patients to rule out brain metastases, but is not required in asymptomatic patients.
  • Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents, other than an aspirin dose less than or equal to 1.3 grams per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam).
  • Unable or unwilling to take folic acid, vitamin B12, or prophylactic corticosteroids.
  • Recent (within 30 days before enrollment) or concurrent yellow fever vaccination.
  • Pregnant or breast-feeding
  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: NCT01057589

Locations
Belgium
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.
Edegem, Belgium, 2650
France
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.
Saint Herblain, France, 44805
Germany
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.
Dresden, Germany, 01307
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.
Essen, Germany, 45122
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.
Hannover, Germany, 30625
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.
Leipzig, Germany, 04103
Italy
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.
Milano, Italy, 20133
Spain
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.
Barcelona, Spain, 08041
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.
Madrid, Spain, 28041
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.
Pamplona, Spain, 31008
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.
Valencia, Spain, 46014
United Kingdom
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.
Cardiff, South Glamorgan, United Kingdom, CF14 2TL
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, United Kingdom, SW3 6JJ
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 - 5PM Eastern time (UTC/GMT - 5 hours, EST Eli Lilly and Company
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01057589     History of Changes
Other Study ID Numbers: 12170, H3E-MC-S123
Study First Received: January 20, 2010
Results First Received: February 6, 2013
Last Updated: September 5, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ethics Committee
Spain: Spanish Agency of Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Eli Lilly and Company:
Pharynx
Larynx
Cervical esophagus
Nose
Thyroid Gland
Parathyroid Gland

Additional relevant MeSH terms:
Neoplasms
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Neoplasms by Site
Pemetrexed
Cetuximab
Cisplatin
Folic Acid
Hydroxocobalamin
Vitamin B Complex
Vitamin B 12
Vitamins
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Hematinics
Hematologic Agents
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on August 21, 2014