Patients with one of following metastatic tumours: - Metastatic colorectal cancer - Metastatic non-small lung cancer - Metastatic renal cell carcinoma MedDRA version: 19.0 Level: PT Classification code 10050513 Term: Metastatic renal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 19.0 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benig
Conditions
Interventions
Product Name: atezolizumab
Product Code: MPDL3280A
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
Other descriptive name: MPDL3280A
Concentration unit: mg/ml milligram(s)
Sponsors
Gustave Roussy
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must be 18 years of age or older. 2. Histologically or cytologically proven metastatic solid tumours including: colorectal (CRC, Microsatellite instability negative and positive), non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC). 3. Patients with at most 5 measurables metastases by RECIST 1.1. At least one of them eligible for SABR in terms of dose constraints at organ at risk and = 4 cm. At least one of them not treated but evaluable by RECIST 1.1. 4.Evaluation by a radiation oncologist within 45 days prior to study registration, including imaging workup to document metastases 5. The irradiated and unirradiated tumour sites must be accessible to tumour biopsy (additional written consent required) 6. Patients may not have used any systemic anticancer treatment (approved or investigational agent) within 4 weeks prior to being enrolled into this study. 7. Life expectancy of more than 3 months 8. Patients must have adequate organ function 9. Patients must be affiliated to a social security system 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 120 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1. Metastases located to the brain and with clinical signs and/or leptomingeal carcinomatosis, or with indistinct borders making targeting not feasible 2. Metastasis localized to the central part of the chest and requiring irradiation 3. Irradiation by SABR should not include metastases located within 3 cm of the previously irradiated structures: * Spinal cord previously irradiated to > 40 Gy * Brachial plexus previously irradiated to > 50 Gy * Small intestine, large intestine, or stomach previously irradiated to > 45 Gy * Brainstem previously irradiated to > 50 Gy * Lung previously irradiated with prior V20Gy > 30% 4. Irradiation required for cord compression and for superior veina cava syndrome. 5. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-PD1, or anti-PDL1 therapeutic antibodies Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided at least 5 half-lives (approximately 75 days) 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 (NCI CTCAE Grade 3 and 4) 6. Treatment with systemic immunostimulatory agents (including but not limited to interferon-alpha (IFN-a) and interleukin-2 (IL-2) within 4 weeks or five half-lives of the drug (whichever is shorter) prior to Cycle 1, Day 1 7. Active or History of autoimmune or inflammatory disease Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen are eligible Patients with vitiligo or psoriasis or grave’s disease, not requiring systemic treatment within the last 2 years, are eligible 8. Any malignancy other than the disease under study in the past 5 years excepting skin cancers such as BCC or SCC 9. Uncontrolled tumour-related pain. Patients requiring pain medication must be on a stable regimen at study entry. Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not presently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment. 10. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters (e.g., PleurX) are allowed. 11. Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or Ca > 12 mg/dL or corrected serum calcium > ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab. Patients who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible. However, patients who are receiving denosumab prior to enrollment must be eligible to receive bisphosphonate instead and willing to switch to bisphosphonate therapy while on the study. 12. Severe active co-morbidity as defined in the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine, in each cohort, the 1 year PFS rate (based on RECIST v1.1.) under combined SABR and anti-PDL1 atezolizumab therapy ;Secondary Objective: 1. Determine the PFS rate under combined SABR and anti-PDL1 atezolizumab therapy 2. Further describe, the efficacy of combination (SABR and atezolizumab) both on the irradiated lesions and the non-irradiated lesions based on tumour response indicators and clinical endpoints 3. Determine the Treatment failure rate 4. Evaluate the toxicity of atezolizumab in combination with SABR ;Primary end point(s): Proportion of patients alive and free of progression at 1 year. Progression is defined using RECIST 1.1. criteria, or death, whatever the cause of death, whichever occurs first.;Timepoint(s) of evaluation of this end point: Tumor evaluation performed at baseline, week 4, week 7, week 13 and then every 12 weeks up to 1 year from treatment initiation or to disease progression, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Delay from treatment initiation to date of progression. Progression is defined using RECIST 1.1. criteria, or death, whatever the cause of death, whichever occurs first. 2. Tumour response indicators and clinical endpoints, assessed according to RECIST v 1.1, modified RECIST (mRECIST) and immune-related response criteria (irRC), are: - Disease Control Rate (DCR) - Objective Response Rate (ORR)R - Duration of response (DOR) - Progression-free survival (PFS) - Time to progression of non-irradiated lesions is computed as the delay from enrollment to the first occurrence of progression outside of the irradiated field - Time to progression of irradiated lesions is computed as the delay from enrollment to the first occurrence of progression of irradiated lesions; - Evaluation of the local control, distant control. 3. Proportion of patients who cannot receive the planned irradiation dose or relative atezolizumab dose intensity below 75% of the initially targeted dose (i.e below 900 mg). 4. AE according to NCI- CTCAE V4.03 scale;Timepoint(s) of evaluation of this end point: 1. Tumor evaluation performed at baseline, week 4, week 7, week 13 and then every 12 weeks up to 1 year after treatment discontinuation or disease progression, whichever occurs first. 2. Tumor evaluation performed at baseline, week 4, week 7, week 13 and then every 12 weeks up to 1 year after treatment discontinuation or disease progression, whichever occurs first. 3. At each treatment administration (every 3 weeks for atezolizumab and on week 4 for SABR) 4. All along the study | — |
Countries
France, Spain
Contacts
Public ContactRegulatory affairs officer
Gustave Roussy
Outcome results
None listed