A Study Comparing Immunotherapy With Chemotherapy in the Treatment of Elderly Patients With Advanced NSCLC (MILES-5)

NCT03975114 | Unknown Phase 2 DMC

• 1 other identifier: MILES-5
• Study Type: interventional
• Target: 460
• Locations: 1 country
• Sites: 1

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

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Eldelry; metastatic Non-Small-Cell Lung Cancer; Durvalumab; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• 12-month overall survival

  12-month overall survival is defined as the Kaplan-Meier (K-M) survival probability at 12 months after randomization (Chen 2015).

  12 months

Study Arms (3)

Chemo first

ACTIVE COMPARATOR

Standard chemotherapy followed at progression by durvalumab

Drug: Chemotherapy; Drug: Durvalumab

Immuno Monotherapy first

EXPERIMENTAL

Experimental single agent immunotherapy with durvalumab followed at progression by chemotherapy

Drug: Chemotherapy; Drug: Durvalumab

Immuno Combination Therapy first

EXPERIMENTAL

experimental single agent immunotherapy with durvalumab followed at progression by chemotherapy

Drug: Chemotherapy; Drug: Durvalumab; Drug: Tremelimumab

Interventions

Chemotherapy DRUG

Any approved first line chemotherapy regimen at Investigators' choice

Chemo first; Immuno Combination Therapy first; Immuno Monotherapy first

Durvalumab DRUG

Durvalumab 1500 mg iv Q4w until progressive or unacceptable toxicity or patient's refusal

Chemo first; Immuno Combination Therapy first; Immuno Monotherapy first

Tremelimumab DRUG

Tremelimumab 75 mg iv Q4w for 4 administrations (4 months)

Immuno Combination Therapy first

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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 1.
• 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)
• Serum creatinine ≤ 1.5 x ULN for the institution (or calculated creatinine clearance ≥ 40 mL/min/1.73 m2).
• Adequate bone marrow function, defined as:
• Haemoglobin \<= 9.0 g/dL
• Absolute neutrophils count (ANC) \>= 1.5 x 109/L (\> 1500 per mm3)
• Platelet count \<= 100 x 109/L(\>100,000 per mm3).

You may not qualify if:

• 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
• Active or prior documented autoimmune disease within the past 2 years (subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment within the past 2 years, are not excluded).
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
• History of allogeneic organ transplant
• History of active primary immunodeficiency.
• Active infection, including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.

Sponsors & Collaborators

• National Cancer Institute, Naples: lead
• University of Campania Luigi Vanvitelli: collaborator
• AstraZeneca: collaborator

Study Sites (1)

Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale

Napoli, 80131, Italy

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Drug Therapy; durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Francesco Perrone, MD, PhD

  Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale

  STUDY CHAIR

Central Study Contacts

Maria Carmela Piccirillo, MD

CONTACT

+390815903615; m.piccirillo@istitutotumori.na.it

Francesco Perrone, MD, PhD

CONTACT

+390815903571; f.perrone@istitutotumori.na.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Comparative Randomized Phase 2 Design

Study Record Dates

• First Submitted: May 31, 2019
• First Posted: June 5, 2019
• Study Start: December 20, 2018
• Primary Completion: December 31, 2023
• Study Completion: June 30, 2024
• Last Updated: March 24, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)