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

NCT02054442 | Unknown Phase 1 DMC

• 3 other identifiers: MOHN012013-002886-20DHNS 2013-01
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Keywords

cetuximab; methotrexate; squamous cell carcinoma head neck; palliative chemotherapy

Outcome Measures

Primary Outcomes (2)

• 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

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

• 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.

  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)

• Overall survival (OS)

  Followed up to 12 months after randomization

• Response rate (RR)

  Till end of treatment

Study Arms (2)

Arm A: MTX in combination with cetuximab

EXPERIMENTAL

The 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.

Drug: Cetuximab; Drug: Methotrexate

Arm B: MTX

ACTIVE COMPARATOR

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.

Drug: Methotrexate

Interventions

Cetuximab DRUG

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.

Also known as: Erbitux, L01XC06

Arm A: MTX in combination with cetuximab

Methotrexate DRUG

Also known as: EMTHEXATE, L01BA01

Arm A: MTX in combination with cetuximab; Arm B: MTX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Merck Serono International SA: collaborator
• Leiden University Medical Center: collaborator
• Academisch Ziekenhuis Maastricht: collaborator
• Erasmus Medical Center: collaborator
• Medisch Spectrum Twente: collaborator
• Medical Center Haaglanden: collaborator
• Elisabeth-TweeSteden Ziekenhuis: collaborator
• Frisius Medisch Centrum: collaborator

Study Sites (8)

Medisch Spectrum Twente

Enschede, Netherlands

Location

Medical Centre Leeuwarden

Leeuwarden, Netherlands

Location

Leiden University Medical Center

Leiden, Netherlands

Location

Academisch Ziekenhuis Maastricht

Maastricht, Netherlands

Location

Radboud university medical center

Nijmegen, Netherlands

Location

Erasmus Medical Center

Rotterdam, Netherlands

Location

Medical Centre Haaglanden

The Hague, Netherlands

Location

St. Elisabeth Ziekenhuis

Tilburg, Netherlands

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Cetuximab; Methotrexate

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Carla M van Herpen, MD, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2014
• First Posted: February 4, 2014
• Study Start: August 1, 2016
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2022
• Last Updated: March 12, 2021

Record last verified: 2021-03

Locations

NL (8)