study of IV vinflunine in combination with methotrexate versus methotrexate alone in patients with recurrent or metastatic head and neck cancer previously treated with platinum-based chemotherapy

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2011-005081-38-EE
• Date of registration: 16/04/2014
• Prospective Registration: Yes
• Primary sponsor: PIERRE FABRE MEDICAMENT
• Public title: study of IV vinflunine in combination with methotrexate versus methotrexate alone in patients with recurrent or metastatic head and neck cancer previously treated with platinum-based chemotherapy
• Scientific title: Phase III study of IV vinflunine in combination with methotrexate versus methotrexate alone in patients with recurrent or metastatic squamous cell carcinoma of the head and neck previously treated with platinum-based chemotherapy (study L00070 IN 309 F0) - NA
• Date of first enrolment: 20/05/2014
• Target sample size: 459
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-005081-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belarus, Belgium, Brazil, Estonia, France, Germany, Israel, Italy, Mexico, Poland, Russian Federation, Slovakia, Spain, Taiwan, Ukraine

Contacts

• Name: Study Monitor
• Affiliation: PIERRE FABRE MEDICAMENT

• Name: Study Monitor
• Affiliation: PIERRE FABRE MEDICAMENT

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients must give written informed consent (personally signed and dated) before completing any study-related procedure
2. Histologically or cytologically confirmed recurrent and/or metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx
3. Documented progressive disease after chemotherapy for locoregionally advanced or recurrent/metastatic SCCHN which included a platinum derivative (cisplatin or carboplatin) that is not suitable for local therapy. Platinum-based chemotherapy can have been associated with cetuximab. Eligible patients include one of the following categories :
- patients who have received induction chemotherapy (ICT) consisting of cisplatin plus 5-fluorouracil or docetaxel plus cisplatin plus 5-fluorouracil followed by radiotherapy alone or chemoradiation (CRT) or radiotherapy concomitant with cetuximab provided that recurrence occurs within 6 months of completing local therapy
- patients who have completed cisplatin-based CRT with or without ICT provided that recurrence occurs within 6 months of completing local therapy. The minimum cumulative dose of cisplatin during CRT must be 200 mg/m².
- patients with recurrent and/or metastatic SCCHN who relapse after platinum-based (cisplatin or carboplatin) chemotherapy given in firstline with an interval < 12 months
- patients with metastatic SCCHN at diagnosis who have been treated with platinum-based (cisplatin or carboplatin) chemotherapy in firstline and relapse with an interval < 12 months. The definition of failure will be as follows :
- refractory disease : progression during platinum-based regimen
- resistant disease : progression during the time from completion of platinum-based chemotherapy but less than 6 months after its completion
- other type of failure : progression > or = 6 months but < 12 months after completion of platinum-based chemotherapy
4. No more than one prior chemotherapy regimen for recurrent/metastatic disease. Prior treatments with targeted therapy used in monotherapy are allowed
5. Minimum interval of 4 weeks between the completion of first-line chemotherapy and randomisation
6. Measurable or non measurable disease
7. WHO performance status < or = 1
8. Age >or = 18 years and < 80 years
9. Adequate haematological function : absolute neutrophil count (ANC) > or = 1.5 x 109/L, platelets > 100 x 109/L, haemoglobin > 10g/dL.
10. Adequate hepatic function : transaminases 11. Adequate renal function : calculated (Cockroft-Gault) creatinine clearance > 60 ml/min
12. Women of childbearing potential must be using a medically accepted method of contraception (barrier methods, oral contraceptive, intrauterine devices) to avoid pregnancy during the 2 months preceding the start of study treatment, throughout the study period and for up to 3 months after the last dose of study treatment in such a manner that the risk of pregnancy is minimised. Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to first treatment administration
13. Fertile men must be us
Exclusion criteria:
1. Nasopharyngeal carcinoma
2. History of brain or leptomeningeal involvement
3. History of other cancers except other synchronous head and neck squamous cell carcinomas, adequately treated in situ carcinoma of the cervix uteri, basal or squamous cell carcinoma of the skin or other cancer curatively treated with surgery and/or radiotherapy (with or without other anti-cancer therapy) and with no evidence of disease for at least 3 years
4. Albumin level < 35 g/L
5. Patients with weight loss >or = 5% within the last 3 months
6. Recurrent pulmonary or upper airways infections (3 times or more in the last 3 months) requiring antibiotics and/or any infection requiring antibiotics within the last month before study entry
7. Grade >or = 2 peripheral neuropathy at study entry according to NCICTC AE (version 3.0)
8. Serum potassium < the lower limit of normal
9. ECG demonstrating a QT/QTc interval > 480 msec
10. A female is not eligible to enter the study if : . Pregnant or lactating . With positive pregnancy test at inclusion
11. Female of childbearing potential who is unwilling or unable to use a medically accepted method to avoid pregnancy during the 2 months preceding the start of study treatment, throughout the study period and at least 3 months following the last dose of study treatment. Male unwilling or unable to use a medically accepted method to avoid pregnancy throughout the study period and at least 3 months following the last dose of study treatment if their partners are women of childbearing potential.
12. Patients with any underlying medical condition that might be aggravated by treatment or which cannot be controlled i.e. active serious infection, poorly controlled diabetes mellitus, concurrent heart failure [New York Heart Association (NYHA) class III-IV] or with progressive or unstable angina, myocardial infarction within 6 months, and/or poorly controlled hypertension.
13. "Third space" fluids (pleural effusion, ascites, massive edema)
14. Concomitant treatment with any other anti-cancer therapy and contraindicated medication (see Section 6.1)
15. Prior treatment with vinca-alkaloids and methotrexate
16. Participation into a clinical study of an investigational agent within 30 days before study entry


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

recurrent or metastatic squamous cell carcinoma of the head and neck previously treated with platinum-based chemotherapy
MedDRA version: 19.0 Level: PT Classification code 10060121 Term: Squamous cell carcinoma of head and neck System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: JAVLOR
Product Name: JAVLOR
Product Code: L0070
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: VINFLUNINE
CAS Number: 162652-95-1
Current Sponsor code: L00070
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Trade Name: Methotrexate Mylan
Product Name: Methotrexate Mylan
Pharmaceutical Form: Solution for injection
INN or Proposed INN: methotrexate
CAS Number: 59-05-2
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Trade Name: Methotrexate Mylan
Product Name: Methotrexate Mylan
Pharmaceutical Form: Solution for injection
INN or Proposed INN: methotrexate
CAS Number: 59-05-2
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Primary end point(s): overall survival

Timepoint(s) of evaluation of this end point: overall survival is defined as time from randomisation to death or last follow-up

Secondary Objective: - to evaluate the response and disease control rate in the 2 study arms
- to assess the response and disease control duration in the 2 study arms
- to assess the progression-free survival in the 2 study arms
- to assess the safety profile in both arms
- to compare the change in disease-related symptoms in the 2 study arms by using the EORTC quality of life questionnaire

Main Objective: to compare the overall survival (OS) of IV vinflunine in combination with methotrexate versus methotrexate alone in incurable recurrent / metastatic SCCHN patients who have failed platinum-based chemotherapy.

Secondary Outcome(s)

Secondary end point(s): - response and disease control rate
- response and disease control duration
- progression-free survival
- safety profile
- to compare the change in disease-related symptoms

Timepoint(s) of evaluation of this end point: efficacy and quality of life: every 6 weeks
safety : day 1 of each cycle and every 6 weeks
demographic data: day 1 of each cycle

Secondary ID(s)

L00070IN309F0

2011-005081-38-DE

Source(s) of Monetary Support

PIERRE FABRE MEDICAMENT

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 06/03/2019
• Date Completed: 23/11/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-005081-38/results