NSCLC, Stage III
Conditions
Keywords
durvalumab, radiotherapy, immunotherapy
Brief summary
Aim of this phase 2 study is to evaluate the safety and the efficacy of the combination of induction chemotherapy plus durvalumab followed by reduced-dose hypo-fractionated thoracic RT (concurrent with durvalumab) and durvalumab maintenance for stage 3 unresectable NSCLC patients candidate to sequential chemo-RT.
Detailed description
The study hypothesis is that the new regimen tested in this study will be safe and effective by: 1. anticipating the use of durvalumab, together with chemotherapy (higher efficacy) 2. harnessing response to induction chemo-durvalumab (which is expected to be significant) to be able to reduce radiotherapy dose without reducing tumor control probability 3. reducing radiation-induced immunosuppression 4. reducing radiation-induced late morbidity, this aspect is important when considering that this regimen is expected to be able to cure a proportion of patients (long-term survivors) In this phase II study, the investigators will evaluate the combination of induction chemotherapy plus durvalumab followed by reduced-dose hypo-fractionated thoracic RT (concurrent with durvalumab) and durvalumab maintenance for stage 3 unresectable NSCLC patients candidate to sequential chemo-RT.
Interventions
DRUGDurvalumab
Patients will receive 1500 mg durvalumab via IV infusion q3w concomitant with chemotherapy (Cisplatin/carboplatin plus etoposide) for up to a maximum of 3 cycles, then via IV infusion at the same interval during sequential radiotherapy and then every 4 weeks for up to a maximum of 12 months or until confirmed disease progression, unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met.
Sponsors
Fondazione IRCCS Policlinico San Matteo di Pavia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
open-label, multi-center, single arm phase 2 trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. 2. Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses. Age 3. 18 years or older at the time of signing the ICF. Type of patient and disease characteristics 4. Histologically- or cytologically-documented NSCLC with locally-advanced, unresectable Stage III disease (according to the IASLC Staging Manual Version 8 \[IASLC 2016\]). Positron emission tomography (PET)/CT, MRI of the brain, and endobronchial ultrasound with biopsy are highly encouraged at diagnosis. 5. Patients with measurable disease assessed at baseline by CT/MRI will be entered in this study. 6. Must have a life expectancy of at least 12 weeks at enrolment. 7. WHO/ECOG PS 0-1. 8. Patient not eligible for concurrent chemo radiation according to investigator assessment 9. Adequate organ and marrow function at enrollment as defined below. These parameters should be achieved without augmentation by growth factors, transfusions, or infusions within 28 days of screening unless required for SoC: 1. Haemoglobin ≥9.0 g/dL; 2. Absolute neutrophil count \>1.0 × 109/L; 3. Platelet count \>75 × 109/L; 4. Serum bilirubin ≤1.5 × upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome, who will be allowed in consultation with their physician. 5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN. 6. Measured creatinine clearance \>40 mL/min or calculated creatinine clearance \>40 mL/min as determined by Cockcroft-Gault (using actual body weight) (Cockcroft and Gault 1976). Males: Creatinine clearance (mL/min) = \[Weight (kg) × (140 - Age)\] / 72 × serum creatinine (mg/dL) Females: Creatinine clearance (mL/min) = \[Weight (kg) × (140 - Age) × 0.85\] / 72 × serum creatinine (mg/dL) 10. Body weight \>30 kg at enrollment 11. Male or female. Reproduction 12. 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: 1. Women \<50 years of age would be considered post-menopausal 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). 2. 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).
Exclusion criteria
Patients should not enter the study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety | Within 6 months from study enrollment | Incidence of Grade 3 or more possibly related adverse events (PRAEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | 0-36 months from study enrollment | Kaplan-Meier Progression-Free Survival, according to RECIST 1.1 and as assessed by the Investigators |
| Overall Survival | 0-36 months from study enrollment | Kaplan-Meier Overall Survival |
Other
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life | 0-36 months | EORTC QLQ-C30 and LC13 |
Countries
Italy
Contacts
Primary ContactAlessandra Ferrari, dr.
Outcome results
None listed