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

February 13, 2019 updated by: University Health Network, Toronto

Phase II Trial of Gemcitabine and Cisplatin/Carboplatin (GC) Plus Erlotinib in Patients With Recurrent and/or Metastatic Nasopharyngeal Cancer

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 Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: GC Plus Erlotinib
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
1000mg/m^2 intravenous (IV) day 1 and day 8
Drug: Carboplatin/Cisplatin
Area under curve (AUC)=5 (Carboplatin) or 70mg/m^2 (Cisplatin) intravenous (IV) day 1
Drug: erlotinib
150mg daily (post GC therapy)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival.
Time Frame: 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.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With the Responses Outlined
Time Frame: Measured every 2 cycles until the participant is off treatment.

Complete Response (CR): disappearance of all clinical and radiological evidence of tumour.

Partial Response (PR): at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD.

Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

Progressive Disease (PD): at least a 20% increase in the sum of LD of measured lesions taking as references the smallest sum LD recorded since the treatment started. Appearance of new lesions will also constitute progressive disease.
Measured every 2 cycles until the participant is off treatment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Collaborators

Hoffmann-La Roche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2006

Primary Completion (Actual)

December 1, 2010

Study Completion (Actual)

April 1, 2011

Study Registration Dates

First Submitted

January 17, 2008

First Submitted That Met QC Criteria

January 28, 2008

First Posted (Estimate)

January 29, 2008

Study Record Updates

Last Update Posted (Actual)

February 28, 2019

Last Update Submitted That Met QC Criteria

February 13, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NPC-774

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Nasopharyngeal Cancer

Clinical Trials on Gemcitabine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Myanmar

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe