A Study of Gemcitabine and Cisplatin/Carboplatin Plus Erlotinib in Patients With Nasopharyngeal Cancer

NCT00603915 | Completed Phase 2 Results DMC

• 1 other identifier: NPC-774
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Cisplatin or Carboplatin will be given on day 1 every 21 days for 6 cycles; Gemcitabine will be given on day 1 and day 8 every 21 days for 6 cycles. Those patients that do not progress on GC after 6 cycles of chemotherapy will be started on erlotinib daily until disease progression. A cycle of erlotinib will be 28 days. Patients who progress on GC will be offered erlotinib as well,in order to evaluate its activity as a single-agent in the second-line setting. Patients previously treated with GC have reported a progression-free survival (PFS) of 9 months. We would anticipate an extension of PFS to 12 months in patients treated with GC followed by maintenance erlotinib. Furthermore, we hypothesize that patients who achieved benefit from GC therapy would have further response when treated with maintenance erlotinib, such that this strategy may increase the likelihood of attaining long-term survival.

Conditions

Nasopharyngeal Cancer

Keywords

gemcitabine; carboplatin; cisplatin; erlotinib; tarceva; nasopharyngeal

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival.

  From randomization to the first documented disease progression or death from any cause, whichever came first, assessed until all participants randomized to the study have progressed for died.

  From the on-study date until the date of first documented progression or date of death from any cause any cause until all participants have progressed or died.

Secondary Outcomes (1)

• Number of Participants With the Responses Outlined

  Measured every 2 cycles until the participant is off treatment.

Study Arms (1)

GC Plus Erlotinib

EXPERIMENTAL

Eligible patients are treated with cisplatin/carboplatin and gemcitabine (GC) for 6 cycles of therapy followed by maintenance erlotinib. Those patients achieving SD or PR with chemotherapy will be started on maintenance erlotinib until disease progression. Those patients achieving CR with chemotherapy will be started on erlotinib for 6 cycles of treatment and those achieving CR on erlotinib will be treated with a maximum of 6 further cycles of erlotinib. Those patients with disease progression while on chemotherapy will be offered erlotinib 2 weeks following the last dose of chemotherapy until further disease progression.

Drug: Gemcitabine; Drug: Carboplatin/Cisplatin; Drug: erlotinib

Interventions

Gemcitabine DRUG

1000mg/m\^2 intravenous (IV) day 1 and day 8

GC Plus Erlotinib

Carboplatin/Cisplatin DRUG

Area under curve (AUC)=5 (Carboplatin) or 70mg/m\^2 (Cisplatin) intravenous (IV) day 1

GC Plus Erlotinib

erlotinib DRUG

150mg daily (post GC therapy)

GC Plus Erlotinib

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed World Health Organization (WHO) type I (keratinizing squamous cell carcinoma) or WHO type II a or b (differentiated non-keratinizing carcinoma or undifferentiated carcinoma) NPC.
• Presence of clinically and/or radiologically documented disease. At least one site of disease must be unidimensionally measurable as follows:
• X-ray, physical exam \> 20 mm
• Spiral CT scan \> 10 mm
• Non-spiral CT scan \> 20 mm
• Investigations including chest x-ray or CT scan of chest, CT or MRI of head and neck (for patients with locally advanced or locally recurrent disease) and other scans as necessary to document all sites of study disease have been performed within 28 days prior to randomization. (Exceptions will be made only for patients who have negative examinations within 35 days prior to registration; exceptions for bone scans will be made for negative examinations within 60 days prior to registration.)
• Age \> 18 years.
• ECOG performance status of 0,1 or 2 (see Appendix II).
• Patients must have a life expectancy of at least 12 weeks.
• Previous Therapy:
• Chemotherapy: Advanced Disease: Patients may not have had prior therapy for recurrent or metastatic disease.
• Curative Therapy: Patients may have had prior chemotherapy (including cisplatin/ carboplatin based regimens) in the neoadjuvant, concurrent and adjuvant setting for locally advanced nasopharyngeal carcinoma provided that 4 weeks have elapsed since treatment and any residual treatment related neuropathy or ototoxicity is \< grade 1 for cisplatin dosing on this trial. Patient with neuropathy or ototoxicity \> grade 2 will be dosed with carboplatin if otherwise eligible for this trial.
• Radiation: Patients may have received prior radiotherapy provided that the last fraction was given at least 4 weeks prior to registration and all toxicities have resolved. If radiotherapy was delivered to the only site of measurable disease, then progression must have been documented in that site after completion of radiotherapy and prior to registration.
• Previous Surgery: Previous major surgery is permitted provided that it has been at least 21 days prior to patient registration and that wound healing has occurred.
• Laboratory Requirements (must be done within 7 days prior to registration)

You may not qualify if:

• Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for \> 5 years.
• Patients with non-measurable disease only. (Please note that bone metastases are considered non-measurable).
• Pregnant or lactating women. However, if the patient is of childbearing potential, a urine β-HCG must be proved negative within 7 days prior to registration. Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation.
• Patients with known brain metastases. (A head CT is not necessary to rule out brain metastases, unless there is clinical suspicion of CNS involvement).
• Serious illness or medical condition, which would not permit the patient to be managed according to the protocol including, but not limited to:
• History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent or limit compliance with study requirements;
• Active uncontrolled infection;
• Symptomatic congestive heart failure, unstable angina, cardiac arrhythmia.
• Prior anti-EGFR monoclonal antibody or tyrosine kinase inhibitors.
• Any inflammatory changes of the surface of the eye.
• Hypersensitivity to erlotinib (Tarceva) or to any of the excipients
• Concomitant requirement for medications classified as CYP3A4 inducer or inhibitor. Inhibitors of CYP3A4 are prohibited beginning at least seven (7) days prior to the administration of the first dose of study medication and for the duration of the study. Inducers of CYP3A4 are prohibited beginning at least fourteen (14) days prior to the administration of the first dose of study medication and for the duration of the study.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Hoffmann-La Roche: collaborator

Study Sites (1)

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

• You B, Le Tourneau C, Chen EX, Wang L, Jarvi A, Bharadwaj RR, Kamel-Reid S, Perez-Ordonez B, Mann V, Siu LL. A Phase II trial of erlotinib as maintenance treatment after gemcitabine plus platinum-based chemotherapy in patients with recurrent and/or metastatic nasopharyngeal carcinoma. Am J Clin Oncol. 2012 Jun;35(3):255-60. doi: 10.1097/COC.0b013e31820dbdcc.

  PMID: 21358293 RESULT

MeSH Terms

Conditions

Nasopharyngeal Neoplasms

Interventions

Gemcitabine; Carboplatin; Cisplatin; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Lillian Siu
• Organization: Univerisity Health Network

lillian.siu@uhn.on.ca

416-946-2911

Study Officials

• Lillian Siu, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: January 17, 2008
• First Posted: January 29, 2008
• Study Start: June 1, 2006
• Primary Completion: December 1, 2010
• Study Completion: April 1, 2011
• Last Updated: February 28, 2019
• Results First Posted: August 10, 2011

Record last verified: 2019-02

Locations

CA (1)