Solide tumors and lymphoma's
Conditions
Interventions
Patients will receive atezolizumab by intravenous (IV) infusion on Day 1 of
each 3 week cycle. The dosing regimen in this study aims to achieve similar
atezolizumab exposures in children and adolesc
PDL1
Pediatrics
Relapsed/Refractory tumor
Sponsors
F. Hoffmann-La Roche Ltd.
Eligibility
Age
2 Years to 64 Years
Inclusion criteria
Inclusion criteria: Patients must meet the following criteria for study entry: * Histologically or cytologically confirmed solid tumor of a type listed below (tumor types with known or expected PD L1 pathway involvement) (including Hodgkin*s and Non Hodgkin*s lymphoma), for which prior treatment had proven to be ineffective (i.e., relapsed or refractory) or intolerable Patients must have had histologic or cytologic confirmation of malignancy at the time of diagnosis or relapse. Neuroblastoma Rhabdomyosarcoma Non-rhabdomyosarcoma soft tissue sarcoma Osteosarcoma Ewing sarcoma Wilms tumor Hodgkin's lymphoma Non-Hodgkin's lymphoma Rhabdoid tumor Note: Patients who have synchronous rhabdoid tumor and atypical teratoid rhabdoid tumor (ATRT) with no clear primary should be enrolled into the rhabdoid tumor cohort, and they should complete the additional assessments scheduled for patients with ATRT. ATRT Other tumor types not included in the list above with documented expression of PD L1 on either tumor cells or immune infiltrating cells with approval of the medical monitor Other tumor types not included in the list above without documented expression of PD-L1 can be included with approval of the medical monitor and should not exceed 20% of the total sample size * Signed Informed Consent Form * Signed Child's or Young Adult*s Assent Form when appropriate, as determined by patient's age and individual site and country standards * Age at study entry < 30 years The first 5 patients must be *2 years of age (i.e., patients must have reached their 2nd birthday) to ensure safety and tolerability before patients <2 years of age receive their first dose of study drug. These first 5 patients must be followed for either two cycles of treatment or until drug discontinuation, whichever is shorter, prior to enrolling younger patients. The Sponsor may decide to stop enrollment of patients who are * 18 years old at any time during the study to ensure adequate enrollment of patients < 18 years old. Patients who are * 18 years old and are eligible for an adult PD L1 treatment protocol will be preferentially enrolled onto those adult studies. * In exceptional cases of relapsed pediatric tumors in patients * 30 years of age, the Sponsor will consider waiving the age requirement with approval of the Medical Monitor. This waiver is restricted to patients with pediatric specific diseases (i.e., neuroblastoma), for whom clinical trials are unlikely to be available, and will not be extended to patients with tumors that typically occur both in children and adults (i.e., high grade glioma). * Able to comply with the study protocol, in the investigator*s judgment * Weight * 3 kg * Disease that is measurable as defined by Response Evaluation Criteria in Solid Tumors Version 1.1(RECIST v1.1), modified International Neuroblastoma Response Criteria (mINRC), Revised Response Criteria for Malignant Lymphoma, or Response Assessment in Neuro-Oncology (RANO) criteria (as appropriate) or evaluable by nuclear medicine techniques, immunocytochemistry techniques, tumor markers, or other reliable measures * Archival tumor tissue block or 15 freshly cut, unstained, serial slides available for submission, or willingness to undergo a core or excisional biopsy prior to enrollment (fine needle aspiration, brush biopsy and lavage samples are not acceptable) Patients with fewer than 15 slides available
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria will be excluded from study entry: * Known primary CNS malignancy or symptomatic CNS metastases, except ATRT Patients with ATRT must not have tumor brainstem involvement or tumors within 10 mm of the optic chiasm; they must not have a history of intracranial hemorrhage or spinal cord hemorrhage or have had neurosurgical resection, brain biopsy, or radiation to the primary brain tumor within 28 days of Cycle 1, Day 1. * Patients with asymptomatic untreated CNS metastases may be enrolled after consultation with the Medical Monitor, provided all of the following criteria are met: Evaluable or measurable outside the CNS. (Note: this is not required for patients with ATRT). No metastases to brain stem, midbrain, pons, medulla, or cerebellum or within 10 mm of the optic apparatus (optic nerve or chiasm). (Note: ATRT may have metastases in the cerebellum.) No history of intracranial hemorrhage or spinal cord hemorrhage No ongoing requirement for corticosteroids for CNS disease except in ATRT where steroids use is permitted with approval from the Medical Monitor. Patients with ATRT must receive a stable or decreasing dose for * 5 days prior to the baseline magnetic resonance imaging scan and at the time of drug initiation. Patients taking a stable dose of anticonvulsants are permitted No neurosurgical resection or brain biopsy within 28 days prior to Cycle 1, Day 1 * Patients with asymptomatic treated CNS metastases may by enrolled after consultation with the Medical Monitor, provided all the criteria listed above in the above CNS-related exclusion criteria are met as well as the following: Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study No stereotactic radiation or whole-brain radiation within 28 days prior to Cycle 1, Day 1 Screening CNS radiographic study * 4 weeks from completion of radiotherapy and * 2 weeks from discontinuation of corticosteroids * For patients with lymphoma, known CNS lymphoma or leptomeningeal disease * Treatment with high-dose chemotherapy and hematopoietic stem-cell rescue within 3 months prior to initiation of study drug This requirement may be waived at the investigator*s request if the patient has recovered from therapeutic toxicity to the degree specified in the protocol, with approval of the Medical Monitor. * Prior allogeneic hematopoietic stem cell transplantation or prior solid organ transplantation * Treatment with chemotherapy (other than high-dose chemotherapy as described above) or differentiation therapy (such as retinoic acid) or immunotherapy (such as anti-GD2 antibody treatment) within 3 weeks prior to initiation of study drug or, if treatment included nitrosoureas, within 6 weeks prior to initiation of study drug This requirement may be waived at the investigator*s request if the patient has recovered from therapeutic toxicity to the degree specified in the protocol, with approval of the Medical Monitor. * Treatment with thoracic or mediastinal radiotherapy within 3 weeks prior to initiation of study drug * Treatment with hormonal therapy (except hormone replacement therapy or oral contraceptives), immunotherapy, or biologic therapy within 4 weeks or 5 half-lives, whichever is shorter, prior to initiation of st
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary efficacy outcome measures for this study are as follows: * Objective response, defined as a complete or partial response for patients with measurable disease or neuroblastoma patients with evaluable disease at baseline, or a complete response for patients with non-measurable but evaluable disease at baseline (except patients with neuroblastoma) on two consecutive occasions * 4 weeks apart, as determined by the investigator using RECIST v1.1 for patients with solid tumors, mINRC for patients with neuroblastoma, Revised Response Criteria for Malignant Lymphoma for patients with Hodgkin's lymphoma or non Hodgkin's lymphoma, and RANO criteria for patients with ATRT. * Clinical benefit response, defined as objective response or stable disease for at least 6 months, as determined by RECIST v1.1 for patients with osteosarcoma * PFS, defined as the time from initiation of study drug to the first documented occurrence of progressive disease, as determined by the investigator using RECIST v1.1 for patients with solid tumors, mINRC for patients with neuroblastoma, Revised Response Criteria for Malignant Lymphoma for patients with Hodgkin's lymphoma or non Hodgkin*s lymphoma, and RANO criteria for patients with ATRT, or death from any cause, whichever occurs first | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary efficacy outcome measures for this study are as follows: * DOR, defined as the time from the first tumor assessment that supports the patient*s objective response to the time of progressive disease, as determined by the investigator using RECIST v1.1 for patients with solid tumors, mINRC for patients with neuroblastoma, Revised Response Criteria for Malignant Lymphoma for patients with Hodgkin's lymphoma or non Hodgkin's lymphoma, and RANO criteria for patients with ATRT, or death from any cause, whichever occurs first * OS, defined as the time from initiation of study drug to death from any cause * ORR, PFS, and DOR as determined by the investigator using immune modified RECIST v1.1 for patients with other solid tumors and immune related response criteria for patients with neuroblastoma, Hodgkin's lymphoma, or non Hodgkin's lymphoma | — |
Countries
The Netherlands
Outcome results
None listed