Extensive Stage Small Cell Lung Cancer (ES-SCLC)
Conditions
Keywords
Extensive-stage small cell lung cancer, atezolizumab
Brief summary
The goal of this clinical trial is to learn if a combination of atezolizumab and standard chemotherapy works to treat sensitive Extensive-stage Small Cell Lung Cancer, progressing after first-line of treatment. The main questions it aims to answer are: * Does combination of atezolizumab and standard chemotherapy increase overall survival? * What medical problems do participants have when taking combination of atezolizumab and standard chemotherapy? Participants will: * take atezolizumab and standard chemotherapy every 3 weeks for 4 cycles and than atezolizumab every 3 weeks up to 18 cycles. * visit the clinic once every 3 weeks for checkups and tests * perform Radiological assessments after 6 weeks and then every 12 weeks to determine response to treatment.
Detailed description
The CARRY-ON study is a multicenter, prospective, open-label single-arm phase II trial, designed to seek for a signal of efficacy of continuing PD-L1 inhibition in patients with sensitive relapse ES-SCLC by adding atezolizumab to rechallenge carboplatin-etoposide chemotherapy. The trial is planned to enroll 142 patients with sensitive relapse ES-SCLC from 25 Italian centers. Sensitive relapse is defined as SCLC relapsed or progressed to first-line chemo-immunotherapy with PD-L1 inhibition (with either atezolizumab or durvalumab) at least 60 days after the last chemotherapy administration. Eligible patients will receive re-challenge chemotherapy (either carboplatin AUC 4 on day 1 plus etoposide 80 mg/m2 days 1-3 or carboplatin AUC 5 on day 1 plus etoposide 100 mg/m2 days 1-3, at investigator's choice) plus atezolizumab 1200 mg flat dosing on day 1 every 3 weeks until PD, unacceptable toxicity or to a maximum of 4 cycles (induction phase) followed by atezolizumab 1200 mg flat dosing every 3 weeks (maintenance phase) until completion of 1 year of maintenance (up to 18 cycles), progressive disease, unacceptable toxicity, patient refusal or loss of clinical benefit (investigator's choice), whichever occur first. Subjects will attend clinical visits at regular intervals to receive trial treatment and for efficacy and safety assessments. All subjects will be monitored continuously for any AE while on study treatment. Radiological assessment will be performed by computed tomography (CT) scan at week 6 (± 7 days), at week 12 (± 7 days) and every 12 weeks (± 7 days) thereafter. The duration of the study is expected to be a maximum of 45 months. The study recruitment period is expected to be approximately 24 months, maximum treatment duration will be 15 months (3 months of induction and 12 months of maintenance), and subsequent survival follow-up will be a maximum of 6 months.
Interventions
DRUGAtezolizumab
1200 mg IV on day 1 of every 21 days, during induction phase and maintenance phase
DRUGCarboplatin
AUC 4 or 5, depending on patient's characteristics, on day 1 every 21 days during induction phase
DRUGEtoposide
80 mg/sqm or 100 mg/sqm, depending on patient's characteristics, on days 1-2-3 of every 21 days
Sponsors
Roche Pharma AG
Gruppo Oncologico Italiano di Ricerca Clinica
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of small-cell lung cancer (SCLC) (according to WHO classification 2015) confirmed at pathology (histology or cytology). 2. Male or female and ≥ 18 years of age. 3. Life expectancy ≥ 12 weeks. 4. Disease progression at least 60 days after the completion of first-line chemotherapy consisting of at least 4 cycles of platinum-etoposide plus either atezolizumab or durvalumab and have not received any other treatment (except for immunotherapy as maintenance treatment); the 60 day-interval is calculated from the date of the last chemotherapy administration to the date of the first radiologically documented progressive disease. 5. No previous radiotherapy on the only one site disease progression, unless that site had subsequent evidence of progressive disease. 6. Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2. 7. Patients with treated brain metastases (or untreated but asymptomatic) and off steroids or on a stable dose of steroids (≤10 mg of prednisone-equivalent) are also eligible. Radiotherapy must have been completed a minimum of 14 days prior to registration, and patients must have recovered from AEs related to radiotherapy to \< grade 1 (except alopecia) 8. For Females: must be postmenopausal (defined as occurring 12 months after last menstrual period) before the screening visit, or are surgically sterile. If they are of childbearing potential, a negative serum pregnancy test prior to study entry has to be documented; furthermore, they agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form (ICF) through 5 months after the last dose of study drug,or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. 9. For Males: even if surgically sterilized (i.e., post-vasectomy status) agree to practice effective barrier contraception during the entire study treatment period and through 6 months after the last dose of study drug, or practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. 10. Normal baseline laboratory values as specified below: * Absolute neutrophil count (ANC) ≥1500/mm3 * Platelet count ≥ 100 x 109/L (≥100,000/μL) without transfusion * Hemoglobin ≥ 90 g/L (≥ 9 g/dL); patients may be transfused to meet this criterion. * Total bilirubin \< 1.5x the institutional upper limit of normal (ULN) * Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \< 2.5x the institutional ULN (\< 5x if liver function test elevations are due to liver metastases) * Creatinine \< 1.5x institutional ULN or estimated creatinine clearance using the Cockcroft-Gault formula ≥ 30 mL/minute for patients with creatinine levels above institutional limits * For patients not receiving therapeutic anticoagulation: INR and aPTT ≤ 1.5 x ULN * Negative HIV test at screening {with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥ 200/μL, and have an undetectable viral load} * Negative hepatitis B surface antigen (HBsAg) test at screening * Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb at screening accompanied by either of the following: * Negative total hepatitis B core antibody (HBcAb) * Positive total HBcAb test followed by a negative (per local laboratory definition) hepatitis B virus (HBV) DNA testNegative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening The HCV RNA test must be performed for patients who have a positive HCV antibody test. 11. Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks before registration, and otherwise noted in other inclusion/
Exclusion criteria
. 12. Recovered (i.e., ≤ grade 1 toxicity) from effects of prior anticancer therapy, except alopecia. 13. Prior radiotherapy is allowed provided that it has been completed more than 2 weeks before starting protocol treatment and patients have recovered from AEs related to radiotherapy to \< grade 1 14. Ability to comply with protocol requirements. 15. The patient or the patient's legal representative has to be able to provide written informed consent. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| overall survival | through study completion, an average of 1 year | overall survival (OS), defined as the time from the date of registration to the date of death from any cause. Patients still alive at the time of analysis are censored at the last time they are known to be alive. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| frequency of adverse events | 30 days post last dose of study drug | Toxicity will be assessed in the mITT population. Descriptive tables will be produced which provide the worst degree of toxicity measured over all cycles according to the NCI-CTCAE version 5.0 |
| Progression Free Survival | through study completion, an average of 6 months | Progression Free Survival (PFS) defined as the time from the patient registration to the evidence of progressive disease, or death, or the last date the patient was known to be progression-free and alive. |
| Objective response rate | through study completion, an average of 1 year | Objective response rate (ORR) is calculated as the sum of RECIST v1.1-defined CR and PR out of the number of assessable patients with measurable disease at baseline. |
Countries
Italy
Contacts
Primary ContactAndrea Ardizzoni, MD
Backup ContactGiuseppe Lamberti, MD
Outcome results
None listed