Carcinoma, Non-Small-Cell LungPhase 2MILES-5NCT03975114
A Study Comparing Immunotherapy With Chemotherapy in the Treatment of Elderly Patients With Advanced NSCLC (MILES-5)
A Phase 2 study testing Chemotherapy, Durvalumab and Tremelimumab in people with Carcinoma, Non-Small-Cell Lung, run by National Cancer Institute, Naples at 1 site in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 70 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung
- What is being tested?
- Chemotherapy, Durvalumab and Tremelimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 460 participants
- Where
- 1 siteItaly
- Study dates
- 20 Dec 2018to 30 Jun 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 70 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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.
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- 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).
- Written informed consent obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
Who cannot join
- 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).
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- 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.
- Receipt of live attenuated vaccine within 30 days prior to the first dose of study drugs.
- Patients with previous malignancies (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer or surgically resected prostate cancer with normal PSA) are excluded only if the histological diagnosis of the current disease does not definitely support the pulmonary origin.
- Brain metastases or spinal cord compression, unless asymptomatic, previously treated, and stable off steroids and anti-convulsants for at least one month prior to study entry.
- Leptomeningeal carcinomatosis
- Clinically significant cardiovascular disease, including:
- Myocardial infarction or unstable angina pectoris within < 6 months prior to the first study treatment
- New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF)
- Uncontrolled hypertension
- Serious cardiac arrhythmia requiring medication (with the exception of atrial fibrillation or paroxysmal supraventricular tachycardia)
- Peripheral vascular disease > grade 3 (i.e. symptomatic and interfering with activities of daily living requiring repair or revision)
- Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction.
- Serious active infection requiring i.v. antibiotics at enrollment.
- Known hypersensitivity to any of the study drugs or excipients.
- Evidence of any other concomitant pathologies, physical examination or laboratory findings (including but not limited to active peptic ulcer disease or gastritis, active bleeding diatheses or psychiatric illness) or social situation that may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment related complications.
- Radiotherapy treatment to the chest or to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study treatment (patients who have had radiotherapy ≥ 4 weeks prior to the first dose of study treatment, but who are still experiencing acute toxic effects of radiotherapy are also excluded).
- Major surgical procedure within 28 days prior to the first dose of study drugs.
- Male patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of study treatment.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale
Naples, 80131
Alessandro Morabito, MD, +390815903637, a.morabito@istitutotumori.na.it
About this study
Official title: A Randomized Phase 2 Study Comparing Immunotherapy With Chemotherapy in the Treatment of Elderly Patients With Advanced NSCLC (MILES-5)
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
- Being tested
- Chemotherapy, Durvalumab, Tremelimumab
- Keywords
- Eldelry, metastatic Non-Small-Cell Lung Cancer, Durvalumab, Immunotherapy
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChemotherapyDrug
Any approved first line chemotherapy regimen at Investigators' choice
DurvalumabDrug
Durvalumab 1500 mg iv Q4w until progressive or unacceptable toxicity or patient's refusal
TremelimumabDrug
Tremelimumab 75 mg iv Q4w for 4 administrations (4 months)
| Study group | Role | What they receive |
|---|---|---|
| Chemo first | Active comparator | Standard chemotherapy followed at progression by durvalumab Receives: Drug: Chemotherapy; Drug: Durvalumab |
| Immuno Monotherapy first | Experimental | Experimental single agent immunotherapy with durvalumab followed at progression by chemotherapy Receives: Drug: Chemotherapy; Drug: Durvalumab |
| Immuno Combination Therapy first | Experimental | experimental single agent immunotherapy with durvalumab followed at progression by chemotherapy Receives: Drug: Chemotherapy; Drug: Durvalumab; Drug: Tremelimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2019
- Study start20 Dec 2018
- Primary completion31 Dec 2023 (estimated)
- Study completion30 Jun 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Comparative Randomized Phase 2 Design
- Masking
- None (open label)
- Enrolment
- 460 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute, Naples
- Sponsor type
- University, hospital or other
- Collaborators
- University of Campania Luigi Vanvitelli, AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Francesco Perrone, MD, PhD, Study chair, Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03975114
- Sponsor's protocol ID
- MILES-5
- Acronym
- MILES-5
- Status last verified
- Mar 2023
- First submitted
- 31 May 2019
- Last updated
- 24 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Data will be available at request
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase 2 Study Comparing Immunotherapy With Chemotherapy in the Treatment of Elderly Patients With Advanced NSCLC (MILES-5)
- ClinicalTrials.gov ID
- NCT03975114
- Acronym / sponsor ID
- MILES-5 / MILES-5
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Keywords
- Eldelry, metastatic Non-Small-Cell Lung Cancer, Durvalumab, Immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 460 participants (estimated)
- Lead sponsor
- National Cancer Institute, NaplesUniversity, hospital or other
- Collaborators
- University of Campania Luigi Vanvitelli, AstraZeneca
- Study start
- 20 Dec 2018 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 30 Jun 2024 (estimated)
- First posted
- 5 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Comparative Randomized Phase 2 Design
| Arm | Type | Receives |
|---|---|---|
| Chemo first | Active comparator | Drug: Chemotherapy, Drug: DurvalumabStandard chemotherapy followed at progression by durvalumab |
| Immuno Monotherapy first | Experimental | Drug: Chemotherapy, Drug: DurvalumabExperimental single agent immunotherapy with durvalumab followed at progression by chemotherapy |
| Immuno Combination Therapy first | Experimental | Drug: Chemotherapy, Drug: Durvalumab, Drug: Tremelimumabexperimental single agent immunotherapy with durvalumab followed at progression by chemotherapy |
Who may qualify
- Ages
- 70 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (16 listed)
- 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).
Key exclusion criteria (32 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ChemotherapyAny approved first line chemotherapy regimen at Investigators' choice | Drug | Chemo first, Immuno Combination Therapy first, Immuno Monotherapy first |
| DurvalumabDurvalumab 1500 mg iv Q4w until progressive or unacceptable toxicity or patient's refusal | Drug | Chemo first, Immuno Combination Therapy first, Immuno Monotherapy first |
| TremelimumabTremelimumab 75 mg iv Q4w for 4 administrations (4 months) | Drug | Immuno Combination Therapy first |
Primary outcome
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).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2023.
- Individual participant dataSharing planned: No. Data will be available at request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francesco Perrone, MD, PhD study chair
Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Chemotherapy, Durvalumab and Tremelimumab in people with Carcinoma, Non-Small-Cell Lung, run by National Cancer Institute, Naples at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Maria Carmela Piccirillo, MD (+390815903615, m.piccirillo@istitutotumori.na.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
12-month overall survival (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2023.