De-escalation Immunotherapy mAintenance Duration Trial for Stage IV Lung Cancer Patients With Disease Control After Chemo-immunotherapy Induction
DIAL
A Phase II-III Randomized Trial Evaluating Maintenance Pembrolizumab (± Pemetrexed) Until Progression Versus Observation (± Pemetrexed) After 6 Months of Platinum-based Doublet Chemotherapy Plus Pembrolizumab Induction Treatment in Patients With Stage IV Non-Small Cell Lung Cancer (NSCLC)
2 other identifiers
interventional
1,360
1 country
44
Brief Summary
Immunotherapeutic approaches recently have demonstrated clinical efficacy in several cancer types, including melanoma and NSCLC. As a matter of fact, first registration trials of immune-checkpoints inhibitors (ICI) in second-line settings (pembrolizumab as well as nivolumab or atezolizumab) had stated that ICI could be continued until disease progression or not tolerable toxicity, up to 5 years. This is only for the first-line registration studies that the arbitrary maximal duration of treatment of 2 years was set up by the Companies sponsoring such trials. The aim is to study a de-escalation scheme of treatment from 2 years of immunotherapy to 6 months (27-weeks), in patients with controlled disease.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started May 2022
Longer than P75 for phase_2
44 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 14, 2022
CompletedFirst Posted
Study publicly available on registry
February 24, 2022
CompletedStudy Start
First participant enrolled
May 2, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2029
ExpectedApril 1, 2025
March 1, 2025
3 years
February 14, 2022
March 26, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Phase II: 18-month overall survival (OS)
Rate of patients not dead 18 months after inclusion
18 months after inclusion
Phase III: overall survival
Time from date of inclusion to the date of death due to any cause
about 24 months after randomization
Secondary Outcomes (8)
Incidence, nature, and severity of adverse events
about 24 months after randomization
Time until definitive health related quality of life score deterioration
about 24 months after randomization
Change from baseline of EuroQol Quality of Life 5-Dimension 5-Level Scale
about 24 months after randomization
Progression-Free Survival (PFS)
about 24 months after randomization
OS according to histological subtype
about 24 months after randomization
- +3 more secondary outcomes
Study Arms (2)
Arm A : control Arm
ACTIVE COMPARATOR6 months treatment by chemotherapy + pembrolizumab followed by pembrolizumab ± pemetrexed for patients with non-squamous cell carcinoma (SCC) until 2 years max
Arm B : experimental arm
EXPERIMENTAL6 months treatment by chemotherapy + pembrolizumab followed by pemetrexed for patients with non-SCC or observation for patients with SCC
Interventions
Pembrolizumab 200 mg every 3 weeks before randomization
Platinum doublet - 4 cycles: either paclitaxel-carboplatin for patient with SCC or pemetrexed-platinum salt followed by 2 cycles of pemetrexed until reaching the 6 months time-point for randomization Carboplatin AUC 5 for non-squamous cell carcinoma and AUC6 for squamous cell carcinoma every 3 weeks or cisplatin 75 mg/m² every 3 weeks Pemetrexed 500 mg/m² every 3 weeks or paclitaxel 175 mg/m² every 3 weeks
Maintenance pemetrexed after randomization Pemetrexed 500 mg/m² every 3 weeks
Pembrolizumab 200 mg every 3 weeks after randomization
Eligibility Criteria
You may qualify if:
- Signed Written Informed Consent:
- Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care.
- Subjects must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing.
- Patients with histologically confirmed metastatic NSCLC (Stage IV accordingly to 8th classification TNM, UICC 2015). A cytologically-proven NSCLC is allowed if a cytoblock has been prepared.
- PD-L1 tumor content as assessed locally by the investigator center.
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
- Weight loss\< 10% within 3 months of study entry.
- No prior systemic anticancer therapy (including EGFR or ALK inhibitors) given as primary therapy for advanced or metastatic disease.
- Age≥ 18 years, \<75 years
- Life expectancy \> 3 months
- Measurable tumor disease by CT or MRI per RECIST 1.1 criteria
- The Investigator must confirm prior to enrolment that the patient has adequate tumor tissue available. Tumor biopsy should be exploitable for molecular analysis. If archival tissue is either insufficient or unavailable, the patient may still be eligible upon discussion with IFCT.
- Note: Tumor tissue collected after the patient was diagnosed with metastatic disease is preferred.
- Tumor tissue sample must not be from locations previously radiated. Tumor sample must be 1 block or at least 7 unstained slides of analyzable tissue.
- Adequate biological functions:
- +4 more criteria
You may not qualify if:
- Small cell lung cancer or tumors with mixed histology including a SCLC component.
- Note : Sarcomatoid histology is allowed. Neuro-endocrine large cell lung cancer with molecular features of small-cell lung cancer (i.e; Rb loss associated with TP53 mutation) will not be eligible. Other neuro-endocrine large cell subtypes, i.e. with adenocarcinoma features (STK11 or K-Ras mutations) will be eligible. In case of doubt, please contact the sponsor.
- Known EGFR activating tumor mutation (deletion LREA in exon 19, L858R ou L861X mutations in exon 21, G719A/S mutation in exon 18, exon 20 insertion) or HER2 exon 20 insertion (either tissue or plasma cfDNA mutation).
- Known ALK, ROS1, Ret, NTRK, NRG1 gene rearrangement as assessed by immunohistochemistry, FISH or NGS (ADN or ARN) sequencing by local genetics and/or pathology laboratory.
- Previous or active cancer within the previous 3 years (except for treated carcinoma in situ of the cervix, or basal cell skin cancer treated or not). Patients with a prostate adenocarcinoma history within the previous 3 years could be included in case of localized prostate cancer, with good prognostic factors according to d'Amico classification (≤T2a, score de Gleason ≤ 6 and PSA ≤ 10 (ng/ml)) provided they were treated in a curative way (surgery or radiotherapy, without any chemotherapy).
- Superior vena cava syndrome persisting despite VCS stenting.
- Radiotherapy needed at initiation of tumour treatment, except bone palliative radiotherapy on a painful or compressive metastasis, respecting 1 week delay between the end of radiotherapy and the beginning of treatment
- Symptomatic untreated brain metastasis (without previous whole brain radiotherapy or stereotactic ablative brain radiotherapy or without surgical resection). At least 2 weeks delay between the end of radiotherapy and the beginning of induction immunotherapy treatment should be respected. Asymptomatic brain metastasis, not needing corticosteroids greater than 10 mg prednisone equivalent daily or mannitol infusions, are allowed.
- History of previous primary immunodeficiency, organ transplantation needing an immunosuppressive treatment, any immunosuppressive drug within 28 days before randomization date, or history of severe toxicity (grade 3/4) by immune mechanism linked to another immunotherapy treatment.
- Systemic treatment with corticosteroids with greater dose than 10 mg prednisone equivalent daily, within 14 days before initiation of the immunotherapy induction. Inhaled, nasal or topic corticosteroids are allowed.
- History of active autoimmune disease including but not limited to rheumatoid polyarthritis, myasthenia, autoimmune hepatitis, systemic Lupus, Wegener's granulomatosis, vascular thrombosis associated with antiphospholipid syndrome, Sjogren's syndrome with interstitial pulmonary disease, recent Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
- Patients with type I diabetes, or hypothyroidism, or immune cutaneous disease (vitiligo, psoriasis, alopecia) or benign rheumatoid polyarthritis not needing any immunosuppressive systemic treatment, or benign sicca syndrome (Sjogren) without interstitial pulmonary disease, or history of past Guillain-Barre syndrome, totally reversible with no sequelae, no systemic immunosuppressive treatment during the last 20 years, are allowed to be included.
- Active inflammatory intestinal disease (Crohn disease, Hemorrhagic recto-colitis, coeliac disease) or any serious chronic intestinal disease with uncontrolled diarrhea.
- Active uncontrolled infection including tuberculosis, known acute viral hepatitis B and C according to serological tests. Patients with serological sequelae of cured viral hepatitis are allowed to be included. Past primary pulmonary tuberculosis in youth does not consist of a contra-indication. Past tuberculosis disease history does not consist of a contra-indication provided the patient was treated during at least 6 months by anti-tuberculosis antibiotic treatment.
- Known HIV infection
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (44)
Aix-en-Provence - CH
Aix-en-Provence, France
Amiens - Clinique de l'Europe
Amiens, France
Angers - CHU
Angers, France
Avignon - CH
Avignon, France
Besançon - CHU
Besançon, France
Bordeaux - Polyclinique
Bordeaux, France
CHU de Bordeaux
Bordeaux, France
Caen - CHU Côte de Nacre
Caen, 14000, France
Cannes - CH
Cannes, France
Chauny - Centre Hospitalier
Chauny, France
CH
Colmar, France
Centre Georges François Leclerc
Dijon, France
CHRU Grenoble
Grenoble, France
La Roche Sur Yon - CH
La Roche-sur-Yon, 85925, France
CH de Versailles
Le Chesnay, France
Centre Hospitalier - Pneumologie
Le Mans, 72000, France
CHRU de Lille
Lille, France
CHU de Limoges
Limoges, France
Lyon - Hôpital Jean Mermoz
Lyon, France
Marseille - Hôpital Européen
Marseille, France
Meaux - CH
Meaux, France
Metz - Hôpital Robert Schuman
Metz, France
Hôpital Arnaud de Villeneuve
Montpellier, 34295, France
Centre Hospitalier
Mulhouse, 68070, France
Nantes - CHU Hôpital Laënnec
Nantes, France
Nice - CRLCC
Nice, France
Orléans - CHR
Orléans, France
Paris - APHP - Hopital Tenon
Paris, 75020, France
Institut CURIE
Paris, 75248, France
Hôpital Bichat - Claude - Bernard
Paris, France
Reims - CHU
Reims, France
Rouen - CHU
Rouen, France
Centre René Huguenin
Saint-Cloud, 92210, France
CHU Saint-Etienne Pneumologie
Saint-Etienne, 42000, France
Hôpital privé de la Loire
Saint-Etienne, France
Institut de Cancérologie de l'Ouest - René Gauducheau
Saint-Herblain, 44805, France
Saint-Nazaire - Clinique Mutualiste de l'Estuaire
Saint-Nazaire, France
CHU de La Réunion-Site Sud
Saint-Pierre, 97448, France
Centre Hospitalier
Saint-Quentin, 02100, France
Nouvel Hôpital Civil - Hôpitaux Universitaires de Strasbourg
Strasbourg, 67091, France
Centre Hospitalier Intercommunal
Toulon, France
Hôpital Larrey (CHU)
Toulouse, 31059, France
CHRU de Tours
Tours, France
Centre Alexis Vautrin
Vandœuvre-lès-Nancy, 54511, France
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 14, 2022
First Posted
February 24, 2022
Study Start
May 2, 2022
Primary Completion
May 1, 2025
Study Completion (Estimated)
June 1, 2029
Last Updated
April 1, 2025
Record last verified: 2025-03
Data Sharing
- IPD Sharing
- Will share