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

NCT01057589 | Completed Phase 2 Results

• 2 other identifiers: 12170H3E-MC-S123
• Study Type: interventional
• Target: 66
• Locations: 6 countries
• Sites: 13

Brief Summary

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.

Conditions

Head and Neck Neoplasms

Keywords

Pharynx; Larynx; Cervical esophagus; Nose; Thyroid Gland; Parathyroid Gland

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  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.

  Baseline to date of PD or death up to 18.7 months

Secondary Outcomes (5)

• Overall Survival (OS)

  Baseline to date of death up to 18.7 months

• Percent of Participants With a Partial Response (PR) or a Complete Response (CR)

  Date of first response to PD (up to 18.7 months)

• 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

  Baseline, End of Triplet Combination Therapy (up to Cycle 6 [4.2 months]), End of Maintenance Therapy (up to 18.7 months)

• Change From Baseline in Participant Reported EQ-5D Utility Score at End of Triplet Combination Therapy and End of Maintenance Therapy

  Baseline, End of Triplet Combination Therapy (up to 6 cycles [4.2 months]) , End of Maintenance Therapy (up to 18.7 months)

• Change From Baseline in Performance Status Scale for Head and Neck Cancer Patients (PSS-HNC)

  Baseline, Triplet Combination Therapy Cycles 2, 4, 6 (cycle = 21 days) and optional Maintenance Therapy Cycles 1, 3, 5 and 7 (cycle = 21 days)

Study Arms (1)

Pemetrexed + Cisplatin + Cetuximab

EXPERIMENTAL

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; Drug: Cetuximab; Drug: Cisplatin; Dietary Supplement: Folic Acid; Dietary Supplement: Vitamin B12

Interventions

Pemetrexed DRUG

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

Also known as: Alimta, LY231514

Pemetrexed + Cisplatin + Cetuximab

Cetuximab DRUG

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

Pemetrexed + Cisplatin + Cetuximab

Cisplatin DRUG

Triplet Combination Therapy: 75mg/m\^2 administered intravenously on Day 1 of 21 day cycle for up to 6 cycles.

Pemetrexed + Cisplatin + Cetuximab

Folic Acid DIETARY_SUPPLEMENT

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.

Pemetrexed + Cisplatin + Cetuximab

Vitamin B12 DIETARY_SUPPLEMENT

Standard of care dietary supplements: 1000 µg IM during the week preceding the first dose of pemetrexed and every 9 weeks thereafter.

Pemetrexed + Cisplatin + Cetuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (13)

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, 2650, Belgium

Location

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, 44805, France

Location

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, 01307, Germany

Location

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, 45122, Germany

Location

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.

Hanover, 30625, Germany

Location

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, 04103, Germany

Location

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.

Milan, 20133, Italy

Location

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, 08041, Spain

Location

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, 28041, Spain

Location

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, 31008, Spain

Location

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, 46014, Spain

Location

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, London, SW3 6JJ, United Kingdom

Location

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, CF14 2TL, United Kingdom

Location

Related Publications (3)

• Cristy M, Eckerman KF. 1987. Specific absorbed fractions of energy at various ages from internal sources: I. methods. Prepared by the Oak Ridge National Laboratory, Oak Ridge, Tenn.

  BACKGROUND

• Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.

  PMID: 7165009 BACKGROUND

• Vermorken JB, Licitra L, Stohlmacher-Williams J, Dietz A, Lopez-Picazo JM, Hamid O, Hossain AM, Chang SC, Gauler TC. Phase II study of pemetrexed in combination with cisplatin and cetuximab in recurrent or metastatic squamous cell carcinoma of the head and neck. Eur J Cancer. 2013 Sep;49(13):2877-83. doi: 10.1016/j.ejca.2013.05.002. Epub 2013 May 30.

  PMID: 23726971 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms; Laryngeal Diseases; Thyroid Diseases

Interventions

Pemetrexed; Cetuximab; Cisplatin; Folic Acid; Vitamin B 12

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Pterins; Pteridines; Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds, 4 or More Rings; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2010
• First Posted: January 27, 2010
• Study Start: February 1, 2010
• Primary Completion: February 1, 2012
• Study Completion: October 1, 2012
• Last Updated: September 18, 2013
• Results First Posted: March 19, 2013

Record last verified: 2013-09

Locations

ES (4); DE (4); FR (1); GB (2); BE (1); IT (1)