Clinical Trials /

Nivolumab in Patients With Type B3 Thymoma and Thymic Carcinoma (NIVOTHYM)

NCT03134118

Description:

The aim of the phase II Nivothym study is to collect data on activity and toxicity of nivolumab therapy in patients with thymic carcinoma or type B3 thymoma that previously received a first platinum-based chemotherapy.

Related Conditions:
  • Thymic Carcinoma
  • Thymoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab in Patients With Type B3 Thymoma and Thymic Carcinoma (NIVOTHYM)
  • Official Title: Single-arm, Multicentre, Phase II Study of Immunotherapy in Patients With Type B3 Thymoma and Thymic Carcinoma Previously Treated With Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: EORTC-1525
  • SECONDARY ID: 2015-005504-28
  • SECONDARY ID: ETOP 11-16
  • NCT ID: NCT03134118

Conditions

  • Thymoma Type B3
  • Thymic Carcinoma

Interventions

DrugSynonymsArms
NivolumabBMS-936558-01Nivolumab

Purpose

The aim of the phase II Nivothym study is to collect data on activity and toxicity of nivolumab therapy in patients with thymic carcinoma or type B3 thymoma that previously received a first platinum-based chemotherapy.

Trial Arms

NameTypeDescriptionInterventions
NivolumabExperimentalPatients will be centrally registered and will receive nivolumab 240 mg IV every 2 weeks
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

        Relapsed/advanced thymoma B3 and thymic carcinoma not amenable to curative-intent radical
        treatment;

        At least one previous line of platinum-based chemotherapy for advanced disease

          -  Patients treated with neo-adjuvant or adjuvant platinum based chemotherapy combined
             with radical surgical or as part of radical chemoradiotherapy are eligible if
             chemotherapy was completed less than 6 months before enrollment;

          -  Radiological progression documented per RECIST 1.1 during or after completion of
             previous line therapy;

          -  Presence of measurable disease according to RECIST 1.1.

          -  Disease status must be documented by full chest and upper abdomen (including adrenal
             glands) CT and/or MRI within 28 days of study enrollment. If clinically indicated,
             brain imaging must be performed

          -  At least 18 years;

          -  WHO Performance Status (PS) 0-2 Note: for the cohort of patient that will be treated
             with nivolumab and ipilimumab: PS 0-1

          -  Availability of FFPE tumor tissue (a tumour block or 10 unstained slides), notably for
             PD-L1 Immunohistochemistry (IHC) expression assessment. Archival material is allowed.
             Patients will be eligible to participate regardless of the level of PD-L1 expression,
             however tissue must be considered adequate (assessed by a local pathologist) for
             characterization of PD-L1 status as per procedure manual;

          -  Adequate hematological function:

          -  white blood count ≥ 2 × 109/L;

          -  haemoglobin >9 g/dL;

          -  platelet count >100 × 109/L;

          -  Adequate liver function:

          -  Total bilirubin <1.5 × ULN (except subjects with Gilbert Syndrome, who can have total
             bilirubin < 3.0 mg/dL);

          -  ALT and/or AST <2.5 × ULN (< 4 x ULN in case of liver metastasis)

          -  alkaline phosphatase <5 × ULN;

          -  Adequate renal function: calculated creatinine clearance ≥50 mL/min (according to
             Cockroft- Gault, see below);

          -  Female CrCl = ((140 - age in years) x weight in kg x 0.85)/ 72 x serum creatinine in
             mg/dL;

          -  Male CrCl = ((140 - age in years) x weight in kg x 1.00)/72 x serum creatinine in
             mg/dL;

          -  Women of child bearing potential (WOCBP) must have a negative serum pregnancy test
             within 72 hours prior to the first dose of study treatment.

        Note: women of childbearing potential are defined as premenopausal females capable of
        becoming pregnant (i.e. females who have had any evidence of menses in the past 12 months,
        with the exception of those who had prior hysterectomy). However, women who have been
        amenorrheic for 12 or more months are still considered to be of childbearing potential if
        the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight,
        ovarian suppression or other reasons.

          -  Patients of childbearing / reproductive potential should use adequate birth control
             measures, as defined by the investigator, during the study treatment period and for at
             least 5 months for a woman and 7 months for a man after the last study treatment. A
             highly effective method of birth control is defined as a method which results in a low
             failure rate (i.e. less than 1% per year) when used consistently and correctly. Such
             methods include:

          -  Combined (estrogen and progestogen containing) hormonal contraception associated with
             inhibition of ovulation (oral, intravaginal, transdermal)

          -  Progestogen-only hormonal contraception associated with inhibition of ovulation (oral,
             injectable, implantable)

          -  Intrauterine device (IUD)

          -  Intrauterine hormone-releasing system (IUS)

          -  Bilateral tubal occlusion

          -  Vasectomized partner

          -  Sexual abstinence

          -  Female patients who are breast feeding should discontinue nursing prior to the first
             dose of study medication and must not be breast feeding during the trial treatment and
             for a period of at least 5 months following the last administration of trial drug(s).

          -  Before patient registration, written informed consent must be given according to
             ICH/GCP, and national/local regulations

        Exclusion Criteria:

          -  No evidence of active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Patients with previously treated brain metastases may participate provided
             they are clinically stable (i.e. without evidence of progression by imaging for at
             least four weeks prior to the enrollment and any neurologic symptoms have returned to
             baseline), and have not received steroids (for a total equivalent dose of more than
             10mg of prednisone per day) for at least 7 days prior to enrollment;

          -  Prior treatment with anti-PD-1, anti-PD-L1/2, anti- CD137, CTLA-4 modulators;

          -  Current participation to any other clinical research nor treatment with an
             investigational agent or use of an investigational device within 4 weeks of the
             enrollment;

          -  Known history or current evidence of active Hepatitis B (e.g., HBsAg reactive) or C
             (e.g., HCV RNA[qualitative] is detected) or Human Immunodeficiency Virus (HIV)
             (HIV-1/2 antibodies);

          -  Known contra-indications for CT with IV contrast

          -  Chronic use of immunosuppressive agents and/or systemic corticosteroids or any use in
             the last 15 days prior to enrollment

          -  Corticosteroid use as premedication for IV contrast allergies/reactions is allowed;

          -  Daily prednisone at doses up to 10 mg or equivalent doses of any othe corticosteroid
             is allowed for example as replacement therapy

          -  No history of interstitial lung disease (ILD) OR pneumonitis (other than COPD
             exacerbation) that has required oral or IV steroids;

          -  Active autoimmune disease that has required systemic treatment in past 2 years (i.e.
             with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
             Replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment and is allowed;

          -  Live vaccines within 30 days prior to the first dose of study therapy and while
             participating in study. Examples of live vaccines include, but are not limited to, the
             following: measles, mumps, rubella, chicken pox, yellow fever, H1N1 flu, rabies, BCG,
             and typhoid vaccine.

          -  Autoimmune paraneoplastic syndrome requiring immunosuppressive or dedicated treatment.
             A specific attention should be given in order to detect any minor myasthenia signs at
             enrollment; acetylcholine receptor antibodies will be systematically tested when
             symptoms are suggestive of a myasthenia;

          -  History of any other hematologic or primary solid tumor malignancy, unless in
             remission for at least 5 years. A pT1-2 prostatic cancer Gleason score < 6,
             superficial bladder cancer, non melanomatous skin cancer or carcinoma in situ of the
             cervix is eligible;

          -  Previous allogeneic tissue/solid organ transplant;

          -  Active infection requiring therapy;

          -  Surgery or chemotherapy related toxicity (toxicity resolved to grade 1, with the
             exception of alopecia, fatigue, neuropathy and lack of appetite /nausea);

          -  Severe comorbidities that in the opinion of the Investigator might hamper the
             participation to the study and/or the treatment administration;

          -  Any psychological, familial, sociological or geographical condition potentially
             hampering compliance with the study protocol and follow-up schedule; those conditions
             should be discussed with the patient before registration in the trial;
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival Rate (PFSR) at month 6
Time Frame:The Progression Free Survival Rate (PFSR) analysis will be performed at month 6
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:32 months after first patient in
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:32 months after first patient in
Safety Issue:
Description:
Measure:Toxicity according CTCAE version 4.03
Time Frame:32 months after first patient in
Safety Issue:
Description:This study will use the International Common Terminology Criteria for Adverse Events (CTCAE), version 4.03, for adverse event reporting.
Measure:Overall Response Rate (ORR)
Time Frame:32 months after first patient in
Safety Issue:
Description:Overall Response Rate (ORR) will be measured according to RECIST 1.1
Measure:Disease Control Rate (DCR)
Time Frame:32 months after first patient in
Safety Issue:
Description:
Measure:Duration of response
Time Frame:32 months after first patient in
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:European Organisation for Research and Treatment of Cancer - EORTC

Trial Keywords

  • Thymoma
  • Phase II
  • nivolumab
  • Thymic carcinoma

Last Updated

November 4, 2019