Subjects with advanced solid tumor MedDRA version: 20.0 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 100000004864
Conditions
Sponsors
Vall d’Hebron Institute of Oncology (VHIO)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part A: 1. Subjects must have histologically or cytologically confirmed malignancy that is metastatic or unresectable, who have progressed to standard therapy, who are receiving a standard anticancer treatment but no subsequent approved treatment would be available upon progression, who are unable to receive standard therapy, or for whom standard therapy does not exist. 2. Subjects must have ECOG performance status of 0 or 1. 3. Subjects must be 18 year-old or older. 4. Subjects must have measurable disease according to RECIST 1.1. 5. Subjects must have enough tumor tissue for molecular analysis • Subjects providing formalin-fixed paraffin embedded tissue (FFPE) must provide a minimum amount of tissue ranging from 20 to 28 slides depending on the sample tumor cellularity. If there is not enough archival tissue to meet this criterion, the subject must undergo a tumor biopsy. • Subjects providing fresh frozen tissue (FFT) must provide 4 core biopsies or equivalent. FFT must be preferentially collected from a tumor biopsy; hence, patients must have disease amenable to be biopsied. Otherwise, the subject should have FFT stored in a biobank or biorepository. • Efforts will be made to provide FFT in at least one quarter of the participating subjects. The proportion of subjects that might provide FFT might change based on the results from the molecular analysis. • Since some of the tests are performed in FFPE tissue, patients providing FFT from a recent biopsy will have part of the sample processed in FFPE tissue as per Laboratory manual. 6. Subjects must have adequate hematological function: absolute granulocyte count = 1.5 × 109/L, platelet count = 100 × 109/L. 7. Subject must have adequate renal and hepatic function: creatinine clearance = 30ml/min, serum bilirubin = 1.5 × ULN; unless due to Gilbert’s syndrome, AST/ALT = 5 × ULN if liver metastases are present or AST/ALT = 3 × ULN if the subject has no liver involvement. 8. For subjects requiring a tumor biopsy: patients must have adequate coagulation function quick time = 60% 9. Subjects must be willing to participate in a clinical trial with a matched therapy according to the molecular profile of his/her tumor 10.For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of <1% per year (when used consistently and correctly) during the treatment period and for at least 5 months after the last dose of atezolizumab, in case of being included in Part B of the study. Please see protocol for more details. 11.For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined in the protocol 12. Ability to understand and the willingness to sign a written informed consent document. Part B: Inclusion criterion 1/2/3/4 from part A 5. Subjects must be willing to participate in a clinical trial with a matched therapy according to the molecular profile of his/her tumor 6. Subjects must have adequate hematological function: absolute granulocyte count = 1.5 × 109/L, platelet count = 100 × 109/L 7. Subjects must have adequate renal and hepatic function: • Serum creatinine = 1.5 × ULN or creatinine clearance = 30 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation: (140 - age) × (weight in kg) × (0.85 if female)/72 × (serum creatinine in mg/dL) • Serum bilirubin = 1.5 × ULN; with th
Exclusion criteria
Exclusion criteria: Part A: 1.Subjects with known brain metastases or leptomeningeal disease 2.Subjects with spinal cord compression not definitively treated with surgery and/or radiation 3.Subjects with uncontrolled intercurrent illness 4.Subjects with inability to swallow tablets or capsules 5.Subjects with known HIV, hepatitis B or hepatitis C infection 6.Subjects with known history of malabsorption 7.Pregnant and lactating women. Females of childbearing potential must have a negative serum pregnancy test within 14 days prior to Day 1. Part B: 1.Pregnant or breastfeeding women. Females of childbearing potential must have a negative serum pregnancy test within 14 days prior to Day 1. This negative test will be valid for Cycle 1 day 1. In subsequent cycles, serum pregnancy test will be performed on day 1 of each cycle, with a +/- 3 day window, and prior to drug administration. 2.Any approved anticancer therapy within 3 weeks prior to initiation of study treatment. Exception: hormone-replacement therapy or oral contraceptives; alliative radiotherapy for bone metastases > 2 weeks prior to Cycle 1, Day 1. 3.Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the study 4.Treatment with an investigational agent within 4 weeks prior to Cycle 1, Day 1 (or within five half-lives of the investigational product, whichever is longer), with the exception of monoclonal antibodies (4 week wash-out period) 5.Subjects with known unstable brain metastases. Exception: treated brain metastasis which remain stable or responding 6 weeks after completing radiotherapy 6.Uncontrolled intercurrent illness that would limit compliance with study requirements 7.Subjects with active hepatitis B (HBV) or hepatitis C (HCV). Subjects with past HBV infection or resolved HBV infection are eligible. Subjects positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA 8.Significant cardiovascular disease within 3 months prior to Cycle 1, Day 1, unstable arrhythmias or unstable angina. Known left ventricular ejection fraction (LVEF) 1.5mmol/L ionized calcium or Ca > 12mg/dL or corrected serum calcium >ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab 9.Another primary malignancy other than disease under study within 2 years prior to Cycle 1 Day 1, unless consider at low risk of relapse at Investigator discretion 10.Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-PD1, or anti-PDL1 therapeutic antibodies. Subjects who have received prior treatment with anti-CTLA-4 may be enrolled, provided at least 5 half-lives have elapsed from the last dose of anti-CTLA-4 to the first dose of Atezolizumab and there was no history of severe immune-mediated adverse effects from anti-CTLA-4 11.Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug (whichever is longer) prior to Cycle 1, Day 1 12.History of severe allergic, anaphylactic, or other hypersensitivity reactions to c
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the antitumor activity of each matched therapies in small subject populations as a signal finding study. For Module I, the primary objective will be the overall response rate by RECIST 1.1 of atezolizumab in each of the arms of module.;Secondary Objective: To evaluate the clinical benefit of matching therapies in small patient populations. Specific Secondary objective for Module 1: To characterize the safety and tolerability of atezolizumab as assessed by the incidence and severity of adverse events. ;Primary end point(s): • Overall response rate (ORR) by RECIST 1.1 of different targeted agents in molecularly selected small patient populations. Specific Primary Endpoint for Module 1 • Overall response rate by RECIST 1.1 of atezolizumab in each of the arms of module.;Timepoint(s) of evaluation of this end point: At Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Mean progression free survival (PFS by RECIST 1.1) of the patients participating in iBASKET evaluated at the end of the module. • Progression Free Survival (PFS by RECIST 1.1) at 6 months of subjects treated with targeted therapy in iBASKET. • Mean overall survival of subjects treated with targeted therapy in iBASKETevaluated at the end of the module. Specific Secondary Endpoints for Module 1 • To evaluate the safety of atezolizumab in subjects with recurrent or metastatic solid tumors. Continued evaluation during the trial (Module 1).;Timepoint(s) of evaluation of this end point: - Mean progression free survival at the end of the module. - Progression Free Survival at 6 months - Mean overall survival at the end of the module -Safety, continued evaluation during the trial | — |
Countries
France, Germany, Italy, Netherlands, Spain, Sweden, United Kingdom
Contacts
Public ContactSusana Munoz
Vall d’Hebron Institute of Oncology (VHIO)
Outcome results
None listed