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

Primary Purpose

Thymoma Type B3, Thymic Carcinoma

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Nivolumab
Sponsored by
European Organisation for Research and Treatment of Cancer - EORTC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Thymoma Type B3 focused on measuring Thymoma, Phase II, nivolumab, Thymic carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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;

Sites / Locations

  • Institut Jules Bordet
  • Universitair Ziekenhuis Antwerpen (UZA)
  • CHU de Brest
  • CHU de Lyon - Hopital Louis Pradel
  • Centre Francois Baclesse
  • CHU de Grenoble - La Tronche - Hôpital A. Michallon
  • Assistance Publique - Hopitaux de Marseille - Hopital Nord (APHM)
  • Institut Curie- Hopital de Paris
  • CHU Toulouse - Hopital Larrey
  • Gustave Roussy
  • The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis
  • Academisch Ziekenhuis Maastricht
  • Erasmus MC
  • Vall d'Hebron Institut d'Oncologia
  • Hospital Universitario 12 De Octubre
  • UniversitaetsSpital Zurich
  • NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital
  • Royal Marsden Hospital - Chelsea, London
  • Royal Marsden Hospital - Sutton, Surrey
  • The Christie NHS Foundation Trust

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Nivolumab

Arm Description

Patients will be centrally registered and will receive nivolumab 240 mg IV every 2 weeks

Outcomes

Primary Outcome Measures

Progression Free Survival Rate (PFSR) at month 6

Secondary Outcome Measures

Progression Free Survival (PFS)
Overall Survival (OS)
Toxicity according CTCAE version 4.03
This study will use the International Common Terminology Criteria for Adverse Events (CTCAE), version 4.03, for adverse event reporting.
Overall Response Rate (ORR)
Overall Response Rate (ORR) will be measured according to RECIST 1.1
Disease Control Rate (DCR)
Duration of response

Full Information

First Posted
April 26, 2017
Last Updated
February 20, 2023
Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
Collaborators
ETOP IBCSG Partners Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT03134118
Brief Title
Nivolumab in Patients With Type B3 Thymoma and Thymic Carcinoma (NIVOTHYM)
Acronym
NIVOTHYM
Official Title
Single-arm, Multicentre, Phase II Study of Immunotherapy in Patients With Type B3 Thymoma and Thymic Carcinoma Previously Treated With Chemotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 11, 2018 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
July 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
Collaborators
ETOP IBCSG Partners Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thymoma Type B3, Thymic Carcinoma
Keywords
Thymoma, Phase II, nivolumab, Thymic carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
55 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Nivolumab
Arm Type
Experimental
Arm Description
Patients will be centrally registered and will receive nivolumab 240 mg IV every 2 weeks
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
BMS-936558-01
Intervention Description
Patients will be centrally registered and will receive nivolumab 240 mg IV every 2 weeks
Primary Outcome Measure Information:
Title
Progression Free Survival Rate (PFSR) at month 6
Time Frame
The Progression Free Survival Rate (PFSR) analysis will be performed at month 6
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Time Frame
32 months after first patient in
Title
Overall Survival (OS)
Time Frame
32 months after first patient in
Title
Toxicity according CTCAE version 4.03
Description
This study will use the International Common Terminology Criteria for Adverse Events (CTCAE), version 4.03, for adverse event reporting.
Time Frame
32 months after first patient in
Title
Overall Response Rate (ORR)
Description
Overall Response Rate (ORR) will be measured according to RECIST 1.1
Time Frame
32 months after first patient in
Title
Disease Control Rate (DCR)
Time Frame
32 months after first patient in
Title
Duration of response
Time Frame
32 months after first patient in

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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;
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicolas Girard
Organizational Affiliation
Institut Curie, Paris, France
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Solange Peters
Organizational Affiliation
University of Lausanne Hospitals
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut Jules Bordet
City
Brussel
Country
Belgium
Facility Name
Universitair Ziekenhuis Antwerpen (UZA)
City
Edegem
Country
Belgium
Facility Name
CHU de Brest
City
Brest
ZIP/Postal Code
29200
Country
France
Facility Name
CHU de Lyon - Hopital Louis Pradel
City
Bron
ZIP/Postal Code
69500
Country
France
Facility Name
Centre Francois Baclesse
City
Caen
ZIP/Postal Code
14076
Country
France
Facility Name
CHU de Grenoble - La Tronche - Hôpital A. Michallon
City
La Tronche
ZIP/Postal Code
38700
Country
France
Facility Name
Assistance Publique - Hopitaux de Marseille - Hopital Nord (APHM)
City
Marseille
Country
France
Facility Name
Institut Curie- Hopital de Paris
City
Paris
ZIP/Postal Code
75248
Country
France
Facility Name
CHU Toulouse - Hopital Larrey
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
Facility Name
The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis
City
Amsterdam
ZIP/Postal Code
1066
Country
Netherlands
Facility Name
Academisch Ziekenhuis Maastricht
City
Maastricht
ZIP/Postal Code
6202
Country
Netherlands
Facility Name
Erasmus MC
City
Rotterdam
Country
Netherlands
Facility Name
Vall d'Hebron Institut d'Oncologia
City
Barcelona
Country
Spain
Facility Name
Hospital Universitario 12 De Octubre
City
Madrid
Country
Spain
Facility Name
UniversitaetsSpital Zurich
City
Zurich
Country
Switzerland
Facility Name
NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital
City
Glasgow
Country
United Kingdom
Facility Name
Royal Marsden Hospital - Chelsea, London
City
London
Country
United Kingdom
Facility Name
Royal Marsden Hospital - Sutton, Surrey
City
Sutton
Country
United Kingdom
Facility Name
The Christie NHS Foundation Trust
City
Wythenshawe
ZIP/Postal Code
M23 9LT
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
34393061
Citation
Remon J, Girard N, Novello S, de Castro J, Bigay-Game L, Bernabe R, Greillier L, Mosquera J, Cousin S, Juan O, Sampayo M, Besse B. PECATI: A Multicentric, Open-Label, Single-Arm Phase II Study to Evaluate the Efficacy and Safety of Pembrolizumab and Lenvatinib in Pretreated B3-Thymoma and Thymic Carcinoma Patients. Clin Lung Cancer. 2022 May;23(3):e243-e246. doi: 10.1016/j.cllc.2021.07.008. Epub 2021 Jul 20.
Results Reference
derived

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

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