A Randomized Phase 2 Study Comparing Immunotherapy With Chemotherapy in the Treatment of Elderly Patients With Advanced NSCLC (MILES-5)
Overview
- Phase
- Phase 2
- Intervention
- Chemotherapy
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Sponsor
- National Cancer Institute, Naples
- Enrollment
- 460
- Locations
- 1
- Primary Endpoint
- 12-month overall survival
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a randomized phase 2 trial aiming to assess the early efficacy of two experimental treatment sequences.
Three arms are planned; (i) standard chemotherapy followed at progression by single agent immunotherapy with durvalumab (CT), (ii) experimental single agent immunotherapy with durvalumab followed at progression by chemotherapy, (iii) experimental combination immunotherapy with durvalumab+tremelimumab followed at progression by chemotherapy.
The the two experimental strategies will be compared with the standard strategy in terms of 12-month overall survival, time considered informative for the type of treatment and disease
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female \>= 70 years of age.
- •Histological documentation of primary squamous or non squamous non-small cell lung carcinoma.
- •Availability of archived tumor tissue block or newly cut unstained slides for PD-L1 determination.
- •Stage IV or IIIB disease with supraclavear metastatic nodes (according to TNM 7th edition).
- •Clinical or radiologic evidence of disease (at least one measurable or non measurable lesion).
- •ECOG performance status 0 to
- •Life expectancy \> 3 months.
- •Adequate renal and hepatic function, defined as:
- •Total serum bilirubin ≤ 1.5 institutional ULN.
- •AST and/or ALT ≤ 2.5 x ULN for the institution (or ≤ 5 x ULN if liver metastases are present)
Exclusion Criteria
- •Cancer related
- •Activating epidermal growth factor receptor mutation (exon19 deletion or exon 21 L858R mutation or other activating/sensitizing mutations).
- •ALK or ROS1 positive (immunohistochemistry or FISH)
- •Mixed small-cell lung cancer and NSCLC histology.
- •Prior, current or planned treatment related
- •Prior chemotherapy or any other medical treatment for advanced NSCLC (previous neoadjuvant or adjuvant chemotherapy is allowed if \> 6 months previously).
- •Prior exposure to immunomodulatory therapy, including, but not limited to, other anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), anti-programmed cell death1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti PD-L2 antibodies.
- •Current or prior use of immunosuppressive medication within 14 days before the first dose of study treatment (intranasal and inhaled corticosteroids at physiological doses not exceeding 10 mg/day of prednisone or an equivalent corticosteroid are allowed).
- •Any concurrent investigational product or other anticancer treatment.
- •Prior or concomitant conditions or procedures related
Arms & Interventions
Chemo first
Standard chemotherapy followed at progression by durvalumab
Intervention: Chemotherapy
Chemo first
Standard chemotherapy followed at progression by durvalumab
Intervention: Durvalumab
Immuno Monotherapy first
Experimental single agent immunotherapy with durvalumab followed at progression by chemotherapy
Intervention: Chemotherapy
Immuno Monotherapy first
Experimental single agent immunotherapy with durvalumab followed at progression by chemotherapy
Intervention: Durvalumab
Immuno Combination Therapy first
experimental single agent immunotherapy with durvalumab followed at progression by chemotherapy
Intervention: Chemotherapy
Immuno Combination Therapy first
experimental single agent immunotherapy with durvalumab followed at progression by chemotherapy
Intervention: Durvalumab
Immuno Combination Therapy first
experimental single agent immunotherapy with durvalumab followed at progression by chemotherapy
Intervention: Tremelimumab
Outcomes
Primary Outcomes
12-month overall survival
Time Frame: 12 months
12-month overall survival is defined as the Kaplan-Meier (K-M) survival probability at 12 months after randomization (Chen 2015).