• Melanoma: unresectable stage III with macroscopic lymph node, in transit/satellite metastasis or stage IV after = 2 lines of therapy (incl. checkpoint blockade, BRAF inhibitor) • Prostate carcinoma: castration-resistant, 2 lines of chemotherapy failed • CTCL: = stage IIB, = 2 previous lines of treatment MedDRA version: 21.1 Level: PT Classification code 10025670 Term: Malignant melanoma stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps
Conditions
Interventions
Trade Name: TECENTRIQ (atezolizumab)
Product Name: TECENTRIQ (atezolizumab)
Pharmaceutical Form: Infusion
Trade Name: GAZYVA (Obinutuzumab)
Product Name: GAZYVA (Obinutuzumab/
Pharmaceutical Form: In
Sponsors
University of Cologne
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 18 years of age or older 2. Written, signed, and dated informed consent before conduct of any study-specific procedure 3. ECOG performance status of 0-2 4. Life expectancy of more than 6 months 5. Advanced disease: a. Prostate Cancer: Castration resistant metastatic disease, at least 2 prior lines of treatment have failed, known PSA serum level at baseline b. Melanoma: Unresectable stage III melanoma with N3 macroscopic lymph nodes or in-transit/satellite metastases or stage IV melanoma after at least 2 lines of standard treatment including checkpoint blockade (CTLA-4 and PD-L1) and BRAF inhibitor in BRAF mutant tumors. Known PD-L1, PD-1 and BRAF status at baseline level. c. CTCL: = stage IIB, = 2 previous lines of treatment (1 skin directed, 1 systemic); continuing skin directed therapy d. Measurable lesion according to RECIST 1.1/iRECIST/CTCL consensus criteria 6. Recent biopsy confirming the diagnosis (= 4 weeks old) 7. Adequate organ function a. WBC = 2500/µL b. ANC = 1000/µL c. Platelets = 50 x 103/µL d. Hemoglobin = 8 g/dL e. Estimated glomerular filtration rate =30 mL/min/1.73m2 calculated with CKD-EPI or FAS f. AST = 2.5 x ULN for patients without liver metastasis, = 5 x ULN for patients with liver metastasis g. Bilirubin = 1.5 x ULN, (except patients with Gilbert’s Syndrome), total bilirubin less than 3.0 mg/dL) 8. Reproductive Status a. Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception and must agree to use adequate method to avoid pregnancy for at least 5 months after the last dose of Atezolizumab and 18 months after the last dose of Obinutuzumab.. b. WOCB must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of ß-HCG) within one until two weeks prior to the start of obinutuzumab / atezolizumab at time of treatment. c. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving obinutuzumab /atezolizumab and who are sexually active with WOCBP must be willing to adhere to contraception for a period of 5 months post atezolizumab and 18 months post obinutuzumab treatment treatment completion. d. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: - Women >50 years of age would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). - Women =50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 7
Exclusion criteria
Exclusion criteria: 1. Patients, which have treatment alternative other than best supportive care, are not eligible for this clinical trial. 2. Any medical, mental or psychological condition which in the opinion of the investigator would not permit the patient to understand the patient information or complete the study. 3. Concurrent systemic cancer related treatment or immune therapy (including antibodies, immuncheckpoint inhibitors or other immunomodulating agents), ongoing chemotherapy or therapy with any anticancer drug not indicated in the study protocol 4. Prior treatment with atezolizumab or obinutuzumab 5. Any investigational agent(s) within 4 weeks prior to study entry 6. Immuncheckpoint inhibitors, other immunomodulating agents or chemotherapy administered less than 4 weeks before first intake of study drug. 7. Active or history of autoimmune disease that requires ongoing systemic steroids (=10mg daily prednisone equivalent) or immunosuppressive medications (including but not limited to corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor) within 2 weeks prior to study entry. Exceptions are: a. vitiligo or resolved childhood asthma. b. Inhaled or topical steroids adrenal replacement steroid doses =10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease. 8. New and active brain metastasis or meningeosis neoplastica. Note: Patients with stable or treated brain metastasis (e.g. after resection, intra or radiation therapy) are allowed to participate in this trial 9. Active and/or chronic viral, bacterial or fungal infection such as hepatitis B, hepatitis C, hepatitis E, HIV or tuberculosis 10. Active uncontrolled acute life-threatening bacterial, viral or fungal infection (e.g. blood culture positive = 72 treatment start) 11. History of another primary malignancy except for a. Malignancy treated with curative intent and with no known active disease =5 years before the first dose of IP and of low potential risk for recurrence b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease c. Adequately treated carcinoma in situ without evidence of disease 12. Patients with severe cardiovascular disease (e.g. NYHA functional class III or IV, myocardial infarction within 6 months before inclusion, ventricular tachyarrhythmia requiring ongoing treatment, unstable angina pectoris) 13. History of active primary immunodeficiency 14. Major surgery (defined as opening at least one body cavity) within 4 weeks prior to signing of informed consent 15. History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening CT scan 16. Pregnant or breastfeeding females 17. Current treatment within another therapeutic clinical trial with experimental and not approved drugs and treatment combinations 18. Prior allogeneic bone marrow transplantation or prior solid organ transplantation 19. Allergies and Adverse Drug Reaction a. History of allergy to study drug components b. History of severe hypersensitivity reaction to any monoclonal antibody c. History of severe adverse drug reaction (= grade 3) of any monotherapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4 antibodies or other immune checkpoint inhibitors Note: Severe adverse drug reaction (= grade 3) with comination treatment of anti-PD-1, anti-PD-L1, anti-PD-L2 together with anti-CTLA4 antibodies, but resolved withou
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To determine disease control rate (CR, PR, SD) upon treatment with: o Obinutuzumab monotherapy o Combination therapy with obinutuzumab and atezolizumab o Atezolizumab monotherapy (sequential treatment of obinutuzumab and atezolizumab) • To determine induction of an immunosupportive tumor microenvironment by: o Immunoscore improvement (25% increase in CD3+ and CD8+ cell infiltration compared to baseline), 25% decrease of FoxP3+ and CD4+ cells in tumor microenvironment (immunohistochemistry) o Increase of T-cell activation by 25% in MFI or frequency of activated T-cells (peripheral blood) ;Secondary Objective: 1. Evaluation of ORR, PFS, DOR, OS 2. To determine the impact of obinutuzumab treatment on CD20+ cells intratumorally and in the peripheral blood 3. To identify prognostic and predicitive value of intratumoral CD20 expression 4. To identify the prognostic and predictive value of intratumoral CD20 expression 5. To evaluate of safety of obinutuzumab or atezolizumab monotherapy or combination therapy in different cancer entities ;Primary end point(s): The primary endpoint is: • To determine disease control rate (CR, PR, SD) The co-primary/key efficacy endpoints are: • Clinical response (CR, PR or SD) until staging after 4 cycles and immunological response after cycle 2 or 6. • Immunological response after 2 cycles (monotherapy) and clinical response (CR, PR or SD) after cycle 6. ;Timepoint(s) of evaluation of this end point: • Clinical response (CR, PR or SD) until staging after 4 cycles and immunological response after cycle 2 or 6. • Immunological response after 2 cycles (monotherapy) and clinical response (CR, PR or SD) after cycle 6. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints are: • Overall response rate (ORR) • Duration of response (DOR) • Progression-free survival (PFS) • Overall survival (OS) ;Timepoint(s) of evaluation of this end point: 1)until staging after 4 cycles and immunological response after cycle 2 or 6. 2) at last visit | — |
Countries
Germany
Contacts
Public ContactClinical Trials Centre Cologne
Clinical Trials Centre Cologne
Outcome results
None listed