Clinical trial NCT00697905: Combination of Gemcitabine and Carboplatin in Metastatic or Recurrent Nasopharyngeal Carcinoma
Official title: An Open Labeled, Multicentre, Randomized Phase II Trial of Combination Gemcitabine and Carboplatin Chemotherapy in Patients With Metastatic or Recurrent Nasopharyngeal Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nasopharyngeal Carcinoma
Keywords: nasopharyngeal carcinoma
Gemcitabine-Carboplatin
Lead sponsor: Ministry of Health, Malaysia
Sponsor class: OTHER_GOV
First posted: 2008-06-16
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of the study is to assess if gemcitabine in combination with carboplatin as 1st line chemotherapy in patients with metastatic or recurrent nasopharyngeal carcinoma has reasonable efficacy and a favourable toxicity profile that warrants further comparative study. A parallel group of randomly selected patients of equal number to the carboplatin and gemcitabine combination arm will be treated with the cisplatin and 5-FU combination chemotherapy (active control arm).

The hypothesis is that this combination of chemotherapy is at least as active and less toxic than the reference regimen of cisplatin in combination with 5-fluorouracil (5-FU).

Detailed description: 52 patients with metastatic or recurrent nasopharyngeal carcinoma who meet inclusion/exclusion criteria will be enrolled into the trial. After initial screening, patients will attend clinic for baseline examination. Subjects will then be randomly allocated to carboplatin and gemcitabine or cisplatin and 5-FU combinations in a ratio of 1:1. Study visits will occur depending on which arm the patient is on.

An economic evaluation of the costs and benefits of gemcitabine-carboplatin will be implemented within this protocol.

Eligibility criteria: Inclusion Criteria:

1. Written informed consent obtained from patient or parents/guardian.
2. Subject age greater than or equal to 18 years
3. Histologically proven recurrent or metastatic undifferentiated or squamous nasopharyngeal carcinoma, not amenable to local therapy.
4. Measurable disease in distant sites and/or loco-regional sites defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded as \>=10mm with CT scan or MRI. Tumour lesions that are situated in a previously irradiated field are measurable only if the tissue planes are preserved on CT or MRI).
5. Prior concurrent chemotherapy and radiation therapy is permitted.
6. Primary chemo-radiotherapy must be completed at least 6 months prior to study entry.
7. Life expectancy over 3 months.
8. ECOG performance status less than or equal to 2.
9. Patients must have normal organ and marrow function as follows:

   * White blood cell count : \>= 3.0 x 10\^9/L
   * Absolute neutrophil count : \>= 1.5 x 10\^9/L
   * Platelets : \>= 100 x 10\^9/L
   * Total bilirubin : within normal limits
   * AST/ALT/ALP : \<= 2.5 x upper limit of normal
   * Creatinine clearance or estimated GFR : \>=50 mls/min.

Exclusion Criteria:

Patients with any of the following are not eligible for enrollment into the study:

1. Pregnant women are excluded from this study because gemcitabine has potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with gemcitabine, breastfeeding should be discontinued if the mother is treated with gemcitabine. These potential risks may also apply to other agents used in this study.
2. Women of child-bearing potential and men without an adequate contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
3. Prior use of gemcitabine
4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine or carboplatin.
5. Prior lines of chemotherapy for metastatic NPC
6. Prior radiotherapy to the indicator lesion(s) to be measured in the study.
7. Patients receiving any other investigational agents
8. Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
9. Patients with bone-only metastases.
10. Clinically significant cardiac disease (e.g. congestive cardiac failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months.
11. Severe sensorineural hearing loss affecting normal daily activities or requiring the use of hearing aids.
12. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
13. Patients with immune deficiency. They are at increased risk of lethal infections when treated with marrow-suppressive therapy.
14. HIV-positive patients receiving combination antiretroviral therapy. There is a possible pharmacokinetic interaction between antiretroviral and gemcitabine or other agents administered during the study. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

Primary outcomes:
measure: The primary efficacy variable is response to therapy. Response will be evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.
timeFrame: 12 months
Secondary outcomes:
measure: Progression free survival defined as the duration of time from start of treatment to time of disease progression or death, whichever occurs first.
timeFrame: 12 months
measure: Duration of response defined as the interval between the first documented response (CR or PR) and the first documented sign of disease progression or death, whichever occurs first.
timeFrame: 12 months
measure: Safety and tolerability assessments will consist of 1.Monitoring and recording all AE and SAE, 2.Regular monitoring of hematology, blood chemistry and urinary laboratory parameters, 3.Regular performance of physical examinations, including vital signs
timeFrame: 12 months
Other outcomes:
Locations:
city: Ipoh
country: Malaysia
facility: Ipoh Specialist Centre
city: Johor Bahru
country: Malaysia
facility: Johor Specialist Centre
city: Kota Kinabalu
country: Malaysia
facility: Sabah Medical Centre
city: Kuala Lumpur
country: Malaysia
facility: Tung Shin Hospital
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Kubang Kerian
country: Malaysia
facility: Hospital Universiti Sains Malaysia
city: Kuching
country: Malaysia
facility: Normah Medical Specialist Centre
city: Likas
country: Malaysia
facility: Likas Hospital
city: Nilai
country: Malaysia
facility: NCI Cancer Hospital
city: Penang
country: Malaysia
facility: Loh Guan Lye Specialist Centre
city: Penang
country: Malaysia
facility: Penang General Hospital
Study officials:
affiliation: University of Malaya
name: Christina Ng
role: PRINCIPAL_INVESTIGATOR
References: