AzTrials
AzTrials

Squamous Cell Carcinoma of the Head and NeckPhase 1/2COMMENCENCT02054442

A Study of the Combination of Cetuximab and Methotrexate in Recurrent or Metastatic Cancer of the Head and Neck

A Phase 1/2 study testing Cetuximab and Methotrexate in people with Squamous Cell Carcinoma of the Head and Neck, run by Radboud University Medical Center at 8 sites in Netherlands.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

The investigators will perform a randomized phase II study to investigate if the addition of cetuximab to MTX is beneficial for the patient. Because no data on this combination are available the investigators will start with a phase Ib study to investigate the feasibility of the schedule. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cetuximab and Methotrexate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
8 sitesNetherlands
Study dates
Aug 2016to Dec 2022
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Cytologically/histologically-proven SCCHN
  • Recurrent or metastatic SCCHN
  • At least one measurable lesion as determined by RECIST v1.1 is required. Lesions in previously irradiated areas should not be considered measurable unless there is clear evidence of progression in such lesions since the radiotherapy.
  • No prior systemic treatment for recurrent or metastatic disease
  • Primary site: (1) oral cavity, (2) oropharynx, (3) hypopharynx, (4) larynx, or (5) unknown primary squamous cell carcinoma in the head and neck region presenting originally with lymph node metastases (N1-N3).
  • Time between prior treatment and inclusion in the study (> 3 months). Palliative RT in case of painful bone metastases is allowed in phase II and after 4 weeks in phase Ib
Show all 18Show fewer
  • Ineligible (due to medical co-morbidities) or intolerant to platinum-based therapy per medical history or refusing cisplatin-based chemotherapy by the patient
  • WHO performance status 0-2.
  • Age >18 years
  • Adequate organ function and laboratory parameters as defined by:
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109 /L
  • Hemoglobin (Hb) ≥ 9 g/dl 5.6 mmol/l (which may be achieved by transfusion)
  • Platelets (PLT) ≥ 100 x 109/L
  • AST and ALT ≤ 2.5 x ULN (upper limit of normal)
  • Serum bilirubin ≤ 1.5 x ULN
  • Calculated creatinine clearance or MDRD > 60ml/min
  • Recovered from all adverse events (AEs) of previous anti-cancer therapies. AEs related to prior radiotherapy are allowed.
  • Written informed consent

Who cannot join

  • Serious active infections
  • Patients (M/F) with reproductive potential not implementing adequate contraceptives measures
  • Prior treatment with EGFR inhibitors or MTX
  • Concomitant (or within 4 weeks before randomization) administration of any other experimental drug under investigation
  • Concurrent treatment with any other anti-cancer therapy.
  • Central nervous system involvement
Show all 11Show fewer
  • Lung fibrosis
  • Pleural effusion or ascites or other third space effusions
  • History of another malignancy within 2 years prior to starting study treatment, except cured basal cell carcinoma of the skin, excised carcinoma in situ of the cervix, or other head and neck cancer.
  • Pregnancy or lactation
  • Any other condition that would, in the Investigator's judgment, preclude patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g. infection/inflammation, intestinal obstruction, social/psychological complications.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

Netherlands8 sites

  • Medisch Spectrum Twente

    Enschede

  • Medical Centre Leeuwarden

    Leeuwarden

  • Leiden University Medical Center

    Leiden

  • Academisch Ziekenhuis Maastricht

    Maastricht

  • Radboud university medical center

    Nijmegen

  • Erasmus Medical Center

    Rotterdam

  • Medical Centre Haaglanden

    The Hague

  • St. Elisabeth Ziekenhuis

    Tilburg

Other trials in Netherlands

About this study

Official title: A Phase Ib-II Study of the Combination of Cetuximab and Methotrexate in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck. A Study of the Dutch Head and Neck Society

The investigators will perform a randomized phase II study to investigate if the addition of cetuximab to MTX is beneficial for the patient. Because no data on this combination are available the investigators will start with a phase Ib study to investigate the feasibility of the schedule.

Read the detailed description

The addition of cetuximab to cisplatin and 5-FU in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) showed an improvement of overall survival (OS), progression free survival (PFS) and response rate (RR). However, cisplatin and 5-FU are toxic cytostatics for the vulnerable recurrent or metastatic SCCHN patient. As one of the primary goals in these patients is palliation, in some patients treatment with cisplatin, 5-FU and cetuximab is not feasible owing to a low performance score (PS of 2) or the patient refusal to receive chemotherapy, i.e. cisplatin and 5-FU, possibly influencing quality of life negatively.

Methotrexate is a cytostatic which has shown to have modest activity in recurrent or metastatic SCCHN. The RR is between 14 and 20%, the median PFS is 3 months, and there is no improvement in OS, which is only 6 months. Toxicity of MTX is very low. Patients with a PS of 2 can be treated with MTX. Patients refusing treatment with cisplatin, 5-FU and cetuximab, frequently choose MTX as palliative treatment.

No data are available on the combination of cetuximab and MTX. The investigators will perform a randomized phase II study to investigate if the addition of cetuximab to MTX is beneficial, i.e. an improvement in the PFS, for the patient. Because no data on this combination are available the investigators will start with a phase Ib study to investigate the feasibility of the schedule.

Being tested
Cetuximab, Methotrexate
Keywords
cetuximab, methotrexate, squamous cell carcinoma head neck, palliative chemotherapy
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CetuximabDrug

    Also called Erbitux, L01XC06

    We will perform a randomized phase II study to investigate in first line if the addition of cetuximab to MTX is beneficial, i.e. improvement in the PFS, for the patient.

  • MethotrexateDrug

    Also called EMTHEXATE, L01BA01

Study groups in NCT02054442
Study groupRoleWhat they receive
Arm A: MTX in combination with cetuximabExperimentalThe dosage of cetuximab will be i.v. 400 mg/m2 over a period of 2h for the first infusion, followed by infusions of 250 mg/m2 over 1 hour once weekly. Cetuximab will be dissolved in 500 ml NaCl 0.9%. Premedication: H1-receptor antagonist and dexamethasone. The dosage of MTX (Methotrexate) will be i.v. 40 mg/m2 once weekly, administered within 5-10 minutes. MTX will be dissolved in 50 ml NaCl 0.9%. Premedication: ondansetron 8 mg. Treatment will be continued until progressive disease, unacceptable toxicity or refusal by patient.
Receives: Drug: Cetuximab; Drug: Methotrexate
Arm B: MTXActive comparatorThe dosage of MTX (Methotrexate) will be i.v. 40 mg/m2 once weekly, administered within 5-10 minutes. MTX will be dissolved in 50 ml NaCl 0.9%. Premedication: ondansetron 8 mg. Treatment will be continued until progressive disease, unacceptable toxicity or refusal by patient.
Receives: Drug: Methotrexate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of dose limiting toxicity (DLT)

    In the phase Ib study: toxicity scored with CTC v 4.0*; incidence of dose limiting toxicity (DLT) during the first 4 weeks after start of the combination

    Measured: During the first 4 weeks after start of the combination MTX and cetuximab

  2. Progression free survival

    In the phase II study: progression free survival (PFS). The analysis of PFS can be performed as soon as the target event (progression or death) has been observed in 98 of the 114 subjects randomized.

    Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months

Secondary outcomes (2)

  1. Overall survival (OS)

    Overall survival (OS) The analysis of OS can be performed as soon as the target event has been observed in 98 of the 114 subjects randomized.

    Measured: Followed up to 12 months after randomization

  2. Response rate (RR)

    The difference in RR rates between both treatment arms will be analyzed using a stratified Cochran Mantel Haenszel test at a one-sided alpha-level of 0.05. In addition to the response rates in both arms, the odds ratio will be reported together with 90% confidence intervals. The impact of various demographic and disease characteristics (e.g. HPV positivity), on RR will be investigated using an exploratory logistic regression model.

    Measured: Till end of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Feb 2014 (estimated)
  2. Study startAug 2016
  3. Primary completionDec 2021 (estimated)
  4. Study completionDec 2022 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02054442
Sponsor's protocol ID
MOHN01
Other IDs
2013-002886-20, DHNS 2013-01
Acronym
COMMENCE
Status last verified
Mar 2021
First submitted
31 Jan 2014
Last updated
12 Mar 2021
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cetuximab and Methotrexate in people with Squamous Cell Carcinoma of the Head and Neck, run by Radboud University Medical Center at 8 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 12 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose limiting toxicity (DLT) (time frame: During the first 4 weeks after start of the combination MTX and cetuximab). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02054442.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2021; AzTrials last refreshed its copy on 8 Nov 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in