Durvalumab with drug combination versus standard chemotherapy in elderly patients with advanced non‑small cell lung cancer

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What is this study about?

The study examines elderly patients with advanced non‑small cell lung cancer. It compares a treatment plan that begins with durvalumab, an immunotherapy that helps the immune system recognize cancer, followed later by standard chemotherapy, versus the usual approach of starting with chemotherapy and switching to durvalumab when the disease progresses. The chemotherapy drugs that may be used include vinorelbine, pemetrexed, carboplatin, cisplatin, paclitaxel and gemcitabine. Participants are required to have a tumor protein level of PDL1 of at least 25 % or an unknown status.

The purpose is to determine which sequence gives better overall survival after one year and a lower death rate within four months. Participants receive a series of intravenous infusions according to the assigned plan, with regular check‑ups to monitor health, side effects, and quality of life. The study follows each person for several months, recording any changes in disease status and any problems from the medicines.

1 randomization

after joining the study you are assigned to one of two treatment groups. the assignment is done by the study system and you will either receive the experimental drug durvalumab or a standard chemotherapy regimen.

2 initial treatment – durvalumab arm

if you are placed in the durvalumab arm you will receive durvalumab at a dose of 1500 mg. the medication is given by intravenous infusion, meaning it is delivered into a vein through a needle. each infusion is performed at a scheduled study visit.

the study schedule specifies that these infusions continue until disease progression is observed or until the investigator determines that treatment should stop because of safety reasons.

3 initial treatment – chemotherapy arm

if you are placed in the chemotherapy arm you will receive a combination of intravenous drugs. the drugs and their doses are:

vinorelbine 30 mg/m2, pemetrexed 500 mg/m2, carboplatin 450 mg, cisplatin 60 mg/m2, paclitaxel 90 mg/m2, and gemcitabine 1200 mg/m2.

each medication is administered by intravenous infusion during a study visit. the combination is given according to the study schedule and continues until disease progression or until the investigator decides to stop treatment because of safety concerns.

4 clinical assessments

during each treatment visit you will undergo clinical assessments that may include physical examination, blood tests, and imaging studies such as scans. these assessments are performed to monitor your health, check for side effects, and evaluate how the disease is responding to the therapy.

5 evaluation for disease progression

the study team reviews the results of the clinical assessments to determine whether the disease has progressed. progression is defined by standard criteria that compare the size of tumors over time.

6 switch to second‑line therapy

if your disease progresses while you are receiving durvalumab, you will start the chemotherapy regimen described in step 3.

if your disease progresses while you are receiving the chemotherapy regimen, you will start durvalumab as described in step 2.

the new therapy is given by intravenous infusion at the same doses used in the initial phase and continues until further progression or a safety decision to stop.

7 continued monitoring

throughout both the first‑line and second‑line treatment periods you will continue to have regular study visits for clinical assessments, laboratory tests, and imaging. these visits allow the study to record overall survival at 12 months and mortality within 4 months of randomization, which are the primary objectives of the trial.

8 final follow‑up

after the last study treatment you will enter a follow‑up phase. during this phase you will have periodic visits to collect information on survival, quality of life, and any late side effects. the follow‑up continues for at least 12 months from the time of randomization.

Who Can Join the Study?

Be at least 70 years old, male or female.
Have a confirmed diagnosis of non‑small cell lung cancer (a common type of lung cancer) that is either squamous or non‑squamous, shown by tissue testing.
Cancer must be at an advanced stage called Stage IV or Stage IIIC (meaning it has spread beyond the original lung).
Tumor cells must show PD‑L1 expression of 25% or higher, or the test may be missing (only a small number of participants can have missing results).
There must be evidence of disease that can be seen on scans or other tests, either as a measurable lump or a lesion that cannot be measured.
Have an ECOG performance status of 0 or 1 (meaning you are fully active or able to do light work).
Be expected to live more than 3 months.
Have adequate kidney and liver function, shown by blood tests: total bilirubin ≤ 1.5 times the normal limit, AST and/or ALT ≤ 2.5 times normal (or ≤ 5 times if liver metastases are present), and serum creatinine ≤ 1.5 times normal (or calculated creatinine clearance ≥ 40 mL/min/1.73 m²).
Have adequate bone‑marrow function, shown by blood counts: hemoglobin ≥ 9.0 g/dL, absolute neutrophil count ≥ 1.5 × 10⁹/L (≥ 1500 per mm³), and platelet count ≥ 100 × 10⁹/L (≥ 100,000 per mm³).
Provide written informed consent before any study procedures are performed.

Who Cannot Join the Study?

Activating epidermal growth factor receptor (EGFR) mutation (specific genetic changes such as exon 19 deletion or exon 21 L858R, or other similar mutations) – you cannot join if you have this mutation.
ALK or ROS1 positive (test results showing these genes are abnormal, found by special lab methods called immunohistochemistry or FISH) – you cannot join if these genes are present.
Mixed small‑cell lung cancer and non‑small cell lung cancer (NSCLC) histology – you cannot join if your tumor contains both types of lung cancer.
Prior chemotherapy or other medical treatment for advanced NSCLC – you cannot join if you have already received chemotherapy for advanced disease (previous chemotherapy given before surgery or after surgery is allowed only if it was more than 6 months ago).
Prior exposure to immunomodulatory therapy (such as other drugs that target PD‑1, PD‑L1, or PD‑L2 proteins) – you cannot join if you have received these treatments before.
Use of immunosuppressive medication within 14 days before the first study dose (except low‑dose steroids not higher than 10 mg/day of prednisone or equivalent) – you cannot join if you took strong immune‑suppressing drugs recently.
Any other investigational product or anticancer treatment at the same time – you cannot join if you are receiving another experimental drug or cancer therapy.
Active or recent autoimmune disease (your immune system attacking your own body) within the past 2 years – you cannot join if you have such a disease (exceptions: vitiligo, Graves’ disease, or psoriasis that did not need systemic treatment in the past 2 years).
Active or recent inflammatory bowel disease (such as Crohn’s disease or ulcerative colitis) – you cannot join if you have these conditions.
History of allogeneic organ transplant (receiving an organ from another person) – you cannot join.
History of active primary immunodeficiency (a condition where the immune system is weak from birth or early life) – you cannot join.
Active infection, including tuberculosis, hepatitis B (positive surface antigen), hepatitis C, or HIV – you cannot join if you have any of these infections (some resolved hepatitis B or C may be allowed under specific test results).
Receipt of a live attenuated vaccine within 30 days before the first study dose – you cannot join if you had such a vaccine recently.
Previous cancer within the last 5 years, except for adequately treated cervical carcinoma in situ, basal or squamous cell skin cancer, or surgically removed prostate cancer with normal PSA – you cannot join if you had other cancers recently.
Brain metastases or spinal cord compression unless they are without symptoms, have been treated, and you have been off steroids and anti‑seizure medicines for at least one month – you cannot join if you have active brain or spinal disease.
Leptomeningeal carcinomatosis (cancer spread to the membranes covering the brain and spinal cord) – you cannot join.
Significant heart disease, including:
- Heart attack (myocardial infarction) or unstable chest pain (unstable angina) within the past 6 months.
- Congestive heart failure that is moderate or worse (NYHA class II or higher).
- Uncontrolled high blood pressure.
- Serious irregular heartbeat that needs medication (except atrial fibrillation or brief rapid beats called paroxysmal supraventricular tachycardia).
- Severe peripheral vascular disease that limits daily activities and needs surgery.
- Abnormally long QT interval on an ECG (QTc ≥ 470 ms), which can affect heart rhythm.
– you cannot join if you have any of these heart conditions.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Azienda Ospedaliera Universitaria Federico II Di Napoli	Naples	Italy
Azienda Ospedaliera Universitaria Universita’ Degli Studi Della Campania Luigi Vanvitelli	Naples	Italy

Other Sites

Site Name	City	Country
Istituto Oncologico Veneto	Padua	Italy
Ospedale Vito Fazzi Lecce	Lecce	Italy
Azienda Ospedaliero-Universitaria Policlinico G. Rodolico-San Marco Di Catania	Catania	Italy
Azienda Sanitaria Locale Viterbo	Viterbo	Italy
IRCCS Ospedale Sacro Cuore Don Calabria	Negrar di Valpolicella	Italy
IRCCS CROB	Rionero In Vulture	Italy
Ospedale Villa Scassi – Sampierdarena-ASL3-Azienda sociosanitaria ligure	Genoa	Italy
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico	Milan	Italy
Ospedale San Raffaele S.r.l.	Milan	Italy
Universita’ Campus Bio-medico Di Roma	Rome	Italy
Universita’ Degli Studi Di Verona	Verona	Italy
Azienda Sociosanitaria Territoriale Santi Paolo E Carlo	Milan	Italy
Azienda USL Toscana Centro	Prato	Italy
Ospedale Fatebenefratelli Isola Tiberina Gemelli Isola	Rome	Italy
Azienda USL Toscana Sud Est	Arezzo	Italy
Azienda Unita Sanitaria Locale Della Romagna	Faenza	Italy
Fondazione Salvatore Maugeri Clinica Del Lavoro E Della Riabilitazione	Pavia	Italy
Centro Di Riferimento Oncologico Di Aviano	Aviano	Italy
Istituto Europeo Di Oncologia S.r.l.	Milan	Italy
IRCCS Istituto Nazionale Tumori Fondazione Pascale	Naples	Italy
Casa Sollievo Della Sofferenza	San Giovanni Rotondo	Italy
Azienda Unita Sanitaria Locale Di Modena	Carpi	Italy
Azienda Unita Sanitaria Locale Di Piacenza	Piacenza	Italy
Azienda Sanitaria Universitaria Friuli Centrale	Udine	Italy
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone	Palermo	Italy
Azienda Unita Locale Socio Sanitaria N 8 Berica	Vicenza	Italy
Ospedale Santa Maria Goretti Latina	Latina	Italy
AORN San Giuseppe Moscati Avellino	Avellino	Italy
Fondazione I.R.C.C.S. Istituto Neurologico Besta	Milan	Italy
Azienda Ospedaliero-Universitaria Sant’Anna	Ferrara	Italy
Ovyvjwlb Gutajynzo	Catania	Italy
Uut Oftyrvofi Musmjo &scsuab Pykt &losuhwge Pybbyzosemfhmx	Brindisi	Italy
Ayqr Sit Phu	Benevento	Italy
Itwmmsmx Rlfnvtipc Pbp Lx Siadcm Dhb Tzpqfy Dppg Anirwhg Itiy Ssfuyb	Meldola	Italy
Amfmatk Oxwrraxlcml Ncujiuztt Sc Axdtqzs E Beyeqe E C Aquthy Awnvjxbbnsu	Alexandria	Italy
Amlmfww Uua Iioqq Dq Rmyoma Egnzrx	Reggio Emilia	Italy
Udhanoqosw Mfvel Gtujqbn Ox Croxyzwhb	Catanzaro	Italy

Trial status

Country	Status	Recruitment Start
Italy	Not recruiting	20.12.2018

Trial locations

Investigated drugs:

Durvalumab is an immunotherapy medicine that helps the body’s immune system notice and attack lung cancer cells. In this study it is given first to some patients, and to others after their initial chemotherapy stops working.

Vinorelbine is a chemotherapy drug that stops cancer cells from dividing. It is used as part of the standard chemotherapy regimen in the trial.

Pemetrexed is a chemotherapy medicine that blocks the chemicals cancer cells need to grow. It is given together with other chemotherapy drugs in the study.

Carboplatin is a platinum‑based chemotherapy that damages the DNA of cancer cells, making it harder for them to survive. It is one of the chemotherapy options used in the trial.

Cisplatin is another platinum‑based chemotherapy that works in a similar way to carboplatin, causing DNA damage to stop cancer cells from growing.

Paclitaxel is a chemotherapy agent that locks the structures cancer cells use to split, preventing them from multiplying.

Gemcitabine is a chemotherapy drug that looks like a building block of DNA, confusing cancer cells and stopping them from copying their genetic material.

Non‑small cell lung cancer – A type of lung cancer that begins in the cells lining the airways and grows more slowly than some other lung cancers. It often forms a solid tumor that can enlarge over time, pressing on nearby structures such as blood vessels and air passages. As the tumor expands, cancer cells may spread to nearby lymph nodes. Further growth can allow the cells to travel through the bloodstream to distant parts of the body, such as the brain, bones, or liver. The disease progresses through stages, with advanced stages indicating larger tumors and wider spread. Symptoms may become more noticeable as the tumor interferes with normal lung function.

Trial ID:

2024-515326-83-00

Protocol code:

MILES-5

NCT ID:

NCT03975114

Trial Phase:

Therapeutic exploratory (Phase II)

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Durvalumab with drug combination versus standard chemotherapy in elderly patients with advanced non‑small cell lung cancer

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?