Histologically confirmed advanced Thymoma B3 or Thymic carcinoma inoperable (Masaoka Stage IIIb or IV). MedDRA version: 21.1 Level: PT Classification code 10055108 Term: Thymic cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Avelumab
Product Code: [MSB0010718C]
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Avelumab
Current Sponsor code: MSB0010718C
Concentration unit: mg/ml milligram(s)/mil
Sponsors
ISTITUTO EUROPEO DI ONCOLOGIA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Histologically confirmed advanced Thymoma B3 or Thymic carcinoma • Inoperable per local Investigator (Masaoka Stage IIIb or IV). • Progression after treatment with least one platinum containing chemotherapy regimen • Measurable disease (RECIST 1.1). • Age =18 years. • ECOG PS =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: • Medical illness that in the investigator’s opinion cannot be adequately controlled with appropriate therapy or would compromise the patient’s ability to tolerate this therapy, including • Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrolment), myocardial infarction (< 6 months prior to enrolment), unstable angina, transient ischemic attack, deep vein thrombosis or symptomatic pulmonary embolism (< 6 months prior to enrolment), congestive heart failure (= New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication • Known history of testing positive for HIV or known acquired immunodeficiency syndrome. • Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive - Active infection requiring systemic therapy; - Patients with a history of non-infectious pneumonitis that has required a course of oral or intravenous steroids, or interstitial lung disease or pulmonary fibrosis - inflammatory bowel disease • Patients with untreated central nervous system disease. Patients with controlled treated CNS lesions who have undergone surgery or stereotactic radiosurgery and stable for 4 weeks are eligible • Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent, in particular, any autoimmune syndrome typically associated with thymomas (myasthenia gravis, pure red cell aplasia), including patients with positive anti-AChR and/or anti-MuSK antibodies without clinical signs or symptoms of myasthenia gravis. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible • History of a hematologic or primary solid tumor malignancy, unless in remission for at least 2 years. Patients with pT1-2 prostatic cancer Gleason score < 6, superficial bladder cancer, non melanomatous skin cancer or carcinoma in situ of the cervix are eligible • Significantly diseased or obstructed gastrointestinal tract, malabsorption, uncontrolled vomiting or diarrhea or inability to swallow oral medications. • Prior organ transplantation including allogenic stem-cell transplantation. • Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines • Serious psychiatric or medical conditions that could interfere with treatment. • Concurrent therapy with approved or investigational anticancer therapeutics. • Current use of immunosuppressive medication within 7 days prior to start treatment, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses = 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) • Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade = 3)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Overall response rate (ORR: complete response + partial response) according to the RECIST 1.1 citeria;Secondary Objective: •To determine the activity of the combination therapy determined by overall response rate according to modified ITMIG response criteria. •To determine the activity of combination therapy determined by overall response rate according to immune-related response criteria (irRC). •To determine six months progression free survival rate of patients treated with combination therapy.;Primary end point(s): to determine the activity of the combination therapy (avelumab + axitinib) determined by overall response rate (RECIST 1.1) in a cohort of patients with advanced Thymoma B3 or Thymic carcinoma.;Timepoint(s) of evaluation of this end point: Anti-tumor activity will be assessed through radiological tumor assessments conducted at screening, and then every 8 weeks up to 18 months after start treatment and every 12 weeks thereafter until documented confirmed disease progression by investigator assessment . In addition, radiological tumor assessments will also be conducted whenever disease progression is suspected (eg, symptomatic deterioration) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To determine the activity of the combination therapy determined by overall response rate according to modified ITMIG response criteria.; To determine the activity of combination therapy determined by overall response rate according to immune-related response criteria (irRC).; To determine six months progression free survival rate of patients treated with combination therapy.; To evaluate exploratory biomarkers for prediction of response to combination therapy.; To evaluate safety and tolerability of combination therapy.;Timepoint(s) of evaluation of this end point: Anti-tumor activity according with ITMIG and irRC criteria will be assessed through radiological tumor assessments conducted at screening, and then every 8 weeks up to 18 months after start treatment and every 12 weeks thereafter until documented confirmed disease progression by investigator assessment . In addition, radiological tumor assessments will also be conducted whenever disease progression is suspected (eg, symptomatic deterioration).; Anti-tumor activity according with ITMIG and irRC criteria will be assessed through radiological tumor assessments conducted at screening, and then every 8 weeks up to 18 months after start treatment and every 12 weeks thereafter until documented confirmed disease progression by investigator assessment . In addition, radiological tumor assessmen | — |
Countries
Italy
Contacts
Public ContactUFFICIO STUDI CLINICI ED ATTIVITA'
ISTITUTO EUROPEO DI ONCOLOGIA
Outcome results
None listed