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

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ClinicalTrials.gov Identifier: NCT03193931
Recruitment Status : Recruiting
First Posted : June 21, 2017
Last Update Posted : March 6, 2019
Sponsor:
Information provided by (Responsible Party):
AIO-Studien-gGmbH

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)

Condition or disease Intervention/treatment Phase
Cancer of Head and Neck Drug: Pembrolizumab Injection Drug: Methotrexate Injectable Solution Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Patients recieve pembrolizumab or methotrexate
Masking: None (Open Label)
Masking Description: opern label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study Comparing Pembrolizumab With Methotrexate in Elderly, Frail or Cisplatin-ineligible Patients With Head and Neck Cancers
Actual Study Start Date : February 2, 2018
Estimated Primary Completion Date : December 30, 2021
Estimated Study Completion Date : September 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm A
Pembrolizumab 200 mg q3w i.v. until disease progression or non-tolerable toxicity (maximum 2 years)
Drug: Pembrolizumab Injection
Pembrolizumab 200 mg q3w i.v. until disease progression or non-tolerable toxicity (maximum 2 years)

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




Primary Outcome Measures :
  1. Antitumor activity of pembrolizumab in SCCHN [ Time Frame: 1 year ]
    Overall survival (OS) rate


Secondary Outcome Measures :
  1. Quality of life QLQC30 [EORTC QLQ-C30] [ Time Frame: through study completion, an average of 6 years ]
    QLQC30

  2. Quality of life HN35 [EORTCQLQ-H&N35] [ Time Frame: through study completion, an average of 6 years ]
    HN35

  3. Predictive biomarkers [ Time Frame: through study completion, an average of 6 years ]
    molecular-genetic pro-inflammatory markers

  4. Predictive biomarkers [ Time Frame: through study completion, an average of 6 years ]
    PD-L1 expression

  5. Time to failure of strategy (TTFS) [ Time Frame: 1 year ]
    defined as death, progressive disease (PD), treatment discontinuation ( or deterioration of Instrumental Activities of Daily Living (IADL score) by 2 points.

  6. Efficacy of pembrolizumab in SCCHN [ Time Frame: through study completion, an average of 6 years ]
    Objective response rate (ORR) according to RECIST 1.1

  7. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: through study completion, an average of 6 years ]
    Adverse event rates due to treatment with MTX and pembrolizumab in SCCHN measured according to CTCAE 4.03


Other Outcome Measures:
  1. QoL response QLQC30 [ Time Frame: through study completion, an average of 6 years ]
    improvement in QLQC30

  2. QoL response HN35 [ Time Frame: through study completion, an average of 6 years ]
    improvement in HN35

  3. prognostic value of tumor shrinkage [ Time Frame: through study completion, an average of 6 years ]
    objective response rate (ORR) according to RECIST 1.1



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Cooperation and willingness to complete all aspects of the study
  2. Signed 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 [Eastern Cooperative Oncology Group] and/or
    • Calculated CrCl [Creatinine Clearance] <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:

    1. Absolute neutrophil count ≥ 1.5 x 109/L
    2. Thrombocytes ≥ 100 x 109/L
    3. Hemoglobin ≥ 9 g/dL
    4. INR [international normalized ratio] ≤ 1.5 and PPT [partial prothrombin time] ≤ 1.5 x lower limit during the last 7 days before therapy
    5. Bilirubin < 1.5 x lower limit and
    6. AST (GOT) [aspartate aminotransferase] and ALT (GPT) [alanine transaminase] < 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

Exclusion Criteria:

  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 [hepatitis B virus], HCV [hepatitis C virus] 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 toxicity 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 are 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 β-hCG) at Screening.
  22. Any psychiatric illness that would affect the patient's ability to understand the demands of the clinical trial
  23. Patient has already been recruited in this trial (does not include screening failures)
  24. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.
  25. Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG].

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03193931


Contacts
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Contact: Aysun Karatas, Dr. +49 30 8145344 ext 33 info@aio-studien-ggmbh.de
Contact: Ralph Keller +49 30-8145344 ext 34 ralph.keller@aio-studien-ggmbh.de

Locations
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Germany
Medizinsche Hochschule Hannover Recruiting
Hannover, Germany, 30625
Sponsors and Collaborators
AIO-Studien-gGmbH

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Responsible Party: AIO-Studien-gGmbH
ClinicalTrials.gov Identifier: NCT03193931     History of Changes
Other Study ID Numbers: AIO-KHT-0115
First Posted: June 21, 2017    Key Record Dates
Last Update Posted: March 6, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Cisplatin
Pembrolizumab
Methotrexate
Antineoplastic Agents
Antineoplastic Agents, Immunological
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors