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

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Recruiting

CT.gov ID

NCT03134118

Collaborator

ETOP IBCSG Partners Foundation (Other)

Enrollment

Locations

Arm

74.7

Anticipated Duration (Months)

2.8

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Thymoma Type B3 Thymic Carcinoma	Drug: Nivolumab	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

55 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Single-arm, Multicentre, Phase II Study of Immunotherapy in Patients With Type B3 Thymoma and Thymic Carcinoma Previously Treated With Chemotherapy

Actual Study Start Date :

Apr 11, 2018

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Jul 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nivolumab Patients will be centrally registered and will receive nivolumab 240 mg IV every 2 weeks	Drug: Nivolumab Patients will be centrally registered and will receive nivolumab 240 mg IV every 2 weeks Other Names: BMS-936558-01

Arm

Intervention/Treatment

Experimental: Nivolumab

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

Drug: Nivolumab

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

Other Names:

BMS-936558-01

Outcome Measures

Primary Outcome Measures

Progression Free Survival Rate (PFSR) at month 6 [The Progression Free Survival Rate (PFSR) analysis will be performed at month 6]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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;

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Institut Jules Bordet	Brussel	Belgium
2	Universitair Ziekenhuis Antwerpen (UZA)	Edegem	Belgium
3	CHU de Brest	Brest	France	29200
4	CHU de Lyon - Hopital Louis Pradel	Bron	France	69500
5	Centre Francois Baclesse	Caen	France	14076
6	CHU de Grenoble - La Tronche - Hôpital A. Michallon	La Tronche	France	38700
7	Assistance Publique - Hopitaux de Marseille - Hopital Nord (APHM)	Marseille	France
8	Institut Curie- Hopital de Paris	Paris	France	75248
9	CHU Toulouse - Hopital Larrey	Toulouse	France	31059
10	Gustave Roussy	Villejuif	France	94805
11	The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis	Amsterdam	Netherlands	1066
12	Academisch Ziekenhuis Maastricht	Maastricht	Netherlands	6202
13	Erasmus MC	Rotterdam	Netherlands
14	Vall d'Hebron Institut d'Oncologia	Barcelona	Spain
15	Hospital Universitario 12 De Octubre	Madrid	Spain
16	UniversitaetsSpital Zurich	Zurich	Switzerland
17	NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital	Glasgow	United Kingdom
18	Royal Marsden Hospital - Chelsea, London	London	United Kingdom
19	Royal Marsden Hospital - Sutton, Surrey	Sutton	United Kingdom
20	The Christie NHS Foundation Trust	Wythenshawe	United Kingdom	M23 9LT