Study Comparing Pembrolizumab With Methotrexate in Elderly, Frail or Cisplatin-ineligible Patients With Head and Neck Cancers

NCT03193931 | Terminated Phase 2 DMC

• 1 other identifier: AIO-KHT-0115
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

The study is designed as an open-label, randomized, prospective, multicenter, phase II study comparing pembrolizumab with methotrexate in elderly, frail or cisplatin-ineligible patients with squamous carcinoma of the head and neck (HNSCC)

Conditions

Cancer of Head and Neck

Outcome Measures

Primary Outcomes (1)

• Antitumor activity of pembrolizumab in SCCHN

  Overall survival (OS) rate

  1 year

Secondary Outcomes (7)

• Quality of life QLQC30 [EORTC QLQ-C30]

  through study completion, an average of 6 years

• Quality of life HN35 [EORTCQLQ-H&N35]

  through study completion, an average of 6 years

• Predictive biomarkers

  through study completion, an average of 6 years

• Predictive biomarkers

  through study completion, an average of 6 years

• Time to failure of strategy (TTFS)

  1 year

Other Outcomes (3)

• QoL response QLQC30

  through study completion, an average of 6 years

• QoL response HN35

  through study completion, an average of 6 years

• prognostic value of tumor shrinkage

  through study completion, an average of 6 years

Study Arms (2)

Arm A

EXPERIMENTAL

Pembrolizumab 200 mg q3w i.v. until disease progression or non-tolerable toxicity (maximum 2 years)

Drug: Pembrolizumab Injection

Arm B

ACTIVE COMPARATOR

Arm B: Methotrexate (MTX) 40 mg/m2 weekly i.v. until disease progression or non-tolerable toxicity (maximum 2 years)

Drug: Methotrexate Injectable Solution

Interventions

Pembrolizumab Injection DRUG

Pembrolizumab 200 mg q3w i.v. until disease progression or non-tolerable toxicity (maximum 2 years)

Arm A

Methotrexate Injectable Solution DRUG

Methotrexate 40 mg/m2 weekly i.v. until disease progression or non-tolerable toxicity (maximum 2 years)

Arm B

Eligibility Criteria

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

You may qualify if:

• Cooperation and willingness to complete all aspects of the study
• Histological or cytological confirmed recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) not amenable to local therapies
• Progressive disease at study entry
• At least 1 measurable lesion according to RECIST 1.1
• No previous systemic treatment for metastatic disease
• Not eligible for cisplatin-based chemotherapy, defined as:
• ECOG 2 \[Eastern Cooperative Oncology Group\] and/or
• Calculated CrCl \[Creatinine Clearance\] \<60 mL/min (measured by MDRD)
• Age ≥ 18 years
• ECOG performance status 0 - 2
• Brain metastases require completion of local therapy with discontinuation of steroids prior to start of treatment
• 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.
• Adequate bone marrow function, liver and renal function:
• Absolute neutrophil count ≥ 1.5 x 109/L
• Thrombocytes ≥ 100 x 109/L

You may not qualify if:

• Live expectancy less than 3 months
• Nasopharynx carcinoma
• Anticancer treatment during the last 30 days prior to start of treatment, including systemic therapy, radiotherapy or major surgery
• Participation in a clinical trial within the last 30 days prior to study treatment
• History of allogeneic tissue/solid organ transplant
• History of pneumonitis that has required oral or i.v. steroids
• Evidence of interstitial lung disease
• Minor surgery ≤ 24 hours prior first dose of study treatment
• Symptomatic acute cardiovascular or cerebrovascular disease
• Known active HBV \[hepatitis B virus\], HCV \[hepatitis C virus\] or HIV infection
• Has any other active infection requiring systemic therapy.
• Patients with active tuberculosis
• 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)
• 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.
• 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.

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead

Study Sites (1)

Medizinsche Hochschule Hannover

Hanover, 30625, Germany

Location

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: opern label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients recieve pembrolizumab or methotrexate

Study Record Dates

• First Submitted: May 31, 2017
• First Posted: June 21, 2017
• Study Start: February 2, 2018
• Primary Completion: November 24, 2021
• Study Completion: March 23, 2022
• Last Updated: February 6, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)