Brief Title
A Study of Gemcitabine and Cisplatin/Carboplatin Plus Erlotinib in Patients With Nasopharyngeal Cancer
Official Title
Phase II Trial of Gemcitabine and Cisplatin/Carboplatin (GC) Plus Erlotinib in Patients With Recurrent and/or Metastatic Nasopharyngeal Cancer
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Progression Free Survival.
Secondary Outcome
Number of Participants With the Responses Outlined
Condition
Nasopharyngeal Cancer
Intervention
Gemcitabine
Study Arms / Comparison Groups
GC Plus Erlotinib
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
20
Start Date
June 2006
Completion Date
April 2011
Primary Completion Date
December 2010
Eligibility Criteria
Inclusion Criteria:
- 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)
- Hematology:
- granulocytes (AGC) > 1.5 x 109/L
- platelets > 100 x 109/L
- Chemistry:
- AST < 2.5 x UNL
- ALT < 2.5 x UNL
- Creatinine clearance(*) : CrCl > 60mls/min for cisplatin or CrCl between 30
- 59ml/min for Carboplatin
(*) calculated
- Patient consent must be obtained according to local Institutional and/or University
Human Experimentation Committee requirements. The patient must sign the consent form
prior to randomization or registration.
- Patients must be accessible for treatment and follow up.
- Normal serum calcium
Exclusion Criteria:
- 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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Lillian Siu, MD, ,
Location Countries
Canada
Location Countries
Canada
Administrative Informations
NCT ID
NCT00603915
Organization ID
NPC-774
Secondary IDs
NPC-774
Responsible Party
Sponsor
Study Sponsor
University Health Network, Toronto
Collaborators
Hoffmann-La Roche
Study Sponsor
Lillian Siu, MD, Principal Investigator, University Health Network, Toronto
Verification Date
February 2019