A randomized phase II study comparing pembrolizumab with methotrexate in elderly, frail or cisplatin-ineligible patients with head and neck cancers
- Conditions
- Squamous carcinoma of the head and neck (SCCHN)MedDRA version: 21.1Level: PTClassification code 10071540Term: Head and neck cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10067821Term: Head and neck cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-001331-12-DE
- Lead Sponsor
- AIO-Studien-gGmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 100
1.Cooperation and willingness to complete all aspects of the study including participation in the translational research
2.Signed and dated written informed consent must be given prior to study inclusion
3.Histological or cytological confirmed recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) not amenable to local therapies
4.Progressive disease at study entry
5.At least 1 measurable lesion according to RECIST 1.1
6.No previous systemic treatment for metastatic disease
7.Not eligible for cisplatin-based chemotherapy, defined as:
-ECOG 2
and/or
-calculated CrCl <60 mL/min (measured by MDRD)
8.Age = 18 years
9.ECOG performance status 0 - 2
10.Brain metastases require completion of local therapy with discontinuation of steroids prior to start of treatment
11.If of childbearing potential, willingness to use highly effective contraceptive method for the duration of the study and 120 days after last dose, such as combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), vasectomized partner, bilateral tubal occlusion, sexual abstinence. If an oral contraception is used, a barrier method of contraception (e.g. male condom, female condom, cervical cap, diaphragm, contraceptive sponge) has to be applied additionally.
12.Adequate bone marrow function, liver and renal function:
a.Absolute neutrophil count = 1.5 x 109/L
b.Thrombocytes = 100 x 109/L
c.Hemoglobin = 9 g/dL
d.INR = 1.5 and PPT = 1.5 x lower limit during the last 7 days before therapy
e.Bilirubin < 1.5 x lower limit and
f.AST (GOT) and ALT (GPT) < 3 x lower limit (5 x lower limit in case of liver metastases)
13.Tumor block or 20 slides must be available at study inclusion for central pathology testing
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70
1.Live expectancy less than 3 months
2.Nasopharynx carcinoma
3.Anticancer treatment during the last 30 days prior to start of treatment, including systemic therapy, radiotherapy or major surgery
4.Participation in a clinical trial within the last 30 days prior to study treatment
5.History of allogeneic tissue/solid organ transplant
6.History of pneumonitis that has required oral or i.v. steroids
7.Evidence of interstitial lung disease
8.Minor surgery = 24 hours prior first dose of study treatment
9.Symptomatic acute cardiovascular or cerebrovascular disease
10.Known active HBV, HCV or HIV infection
11.Has any other active infection requiring systemic therapy.
12.Patients with active tuberculosis
13.Prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor [TNFR] family), or anti-cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
14.A diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
15.Patient has had a prior monoclonal antibody, which does significantly interfere with the immune system or which does have a systemic therapeutic effect on the tumor within 4 weeks prior to randomization.
16.Patient has not recovered (i.e., = Grade 1 or at baseline) from any toxicities due to agents administered more than 4 weeks earlier. [Subjects with = Grade 2 neuropathy or alopecia are an exception to this criterion and may qualify for the study.]
17.Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen’s syndrome will not be excluded from the study.
18.Has received a live vaccine within 30 days prior to the first dose of trial treatment.
19.Has known hypersensitivity to methotrexate or pembrolizumab or any constituent of the products.
20.Other active malignancy requiring treatment
21.Lactating or pregnant women, women of child-bearing potential who do not agree to the usage of highly effective contraception methods (allowed methods of contraception, meaning methods with a rate of failure of less than 1% per year combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), vasectomized partner, bilateral tubal occlusion, sexual abstinence. If an oral contraception is used, a barrier method of contraception (e.g. male condom, female condom, cervical cap, diaphragm, contraceptive sponge) has to be applied additionally. Women of childbearing potential must have a negative pregnancy test (serum ß-hCG) at Screening.
22.Any psychiatric illness that would affect
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess antitumor activity of pembrolizumab in SCCHN;Secondary Objective: • To assess quality of life (QoL), predictive biomarkers, and efficacy of pembrolizumab in SCCHN.<br>• Safety and tolerability of MTX and pembrolizumab in SCCHN<br>;Primary end point(s): overall survival (OS) rate at 1 year;Timepoint(s) of evaluation of this end point: one year after inclusion of the subject into trial
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Key secondary endpoints: <br>•Time to failure of strategy (TTFS) at 1 year, defined as death, progressive disease (PD), treatment discontinuation (due to toxicity) or deterioration of Instrumental Activities of Daily Living (IADL score) by 2 points<br>•objective response rate (ORR) according to modified RECIST 1.1 <br><br>other secondary endpoints: <br>•progression free survival (PFS)<br>•overall survival (OS)<br>•ORR according to RECIST 1.1<br>•duration of response<br>•duration of treatment beyond progression<br>•treatment discontinuation rate<br>•safety and tolerability <br><br>Exploratory:<br>•predictive value of PD-L1 expression <br>•prognostic value of tumor shrinkage <br>•QoL response, defined as improvement of 5-10 points in QLQC30 and HN35<br>;Timepoint(s) of evaluation of this end point: TTFS: one year after inclusion of a patient into study<br>ORR: after last visit of a patient<br>PFS: after progression/death/loss-to follow-up<br>OS: after death/ cut off<br><br>