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Non-small Cell Lung CancerPhase 1/2IDEARNCT05267392

Neoadjuvant Immunotherapy With Durvalumab (MEDI4736) in Non-Surgical Early Stage or Locally Advanced Non-Small Cell Lung Cancer (NSCLC) Followed by Radical Radiotherapy or Chemoradiotherapy

A Phase 1/2 study testing Durvalumab in people with Non-small Cell Lung Cancer, run by Instituto Portugues de Oncologia, Francisco Gentil, Porto at 1 site in Portugal.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This study proposes to evaluate the safety and efficacy of an anti-PD-L1 (durvalumab) agent as neoadjuvant therapy in patients diagnosed with localized NSCLC who are planned to undergo radical RT or CRT. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-small Cell Lung Cancer
What is being tested?
Durvalumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 sitePortugal
Study dates
16 Feb 2021to Jan 2024
Phase
Phase 1/2
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
  • Age ≥ 18 years at time of screening.
  • ECOG performance status of 0 or 1.
  • Life expectancy of at least 12 weeks.
  • Body weight >30 kg.
  • Histologically documented NSCLC.
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  • Clinical Stage IIIA NSCLC eligible for RT (Initial work-up including PET-CT and brain MRI or brain CT for staging); patients with stage IB (≥ 4 cm)-IIIA NSCLC that are not considered for surgical treatment by the clinical team (e.g.: due to comorbidities) or by patient choice, but are eligible for radical RT or CRT can be proposed for inclusion.
  • Measurable disease, as defined by RECIST.
  • Adequate normal organ and marrow function defined by the following laboratory results obtained within 14 days prior to durvalumab administration:
  • Hemoglobin ≥ 9.0 g/dL.
  • White blood cell (WBC) counts > 2.5 x 109/L.
  • Absolut neutrophil count (ANC) ≥ 1.5 x 109/L (without granulocyte colony-stimulating factor support within 2 weeks prior to durvalumab treatment).
  • Lymphocyte count ≥ 0.5 x 109/L.
  • Platelet count ≥100 x 109/L.
  • AST, ALT, and alkaline phosphatase ≤ 2.5 x the institutional upper limit of normal (ULN).
  • Serum bilirubin ≤ 1.5 x ULN. Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled.
  • International Normalized Ratio (INR) and activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN -This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
  • Serum albumin ≥2.5 g/dL.
  • Calcemia ≤2.65 mmol/L or Ca ≤10 mg/dL.
  • Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance.
  • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  • Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrhoeic for 12 months without an alternative medical cause. The following age-specific requirements apply:
  • Women <50 years of age would be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
  • Women ≥50 years of age would be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
  • Women of Childbearing Potential must be willing to use 1 highly effective method of contraception, or to abstain from sexual activity, from the time of screening throughout the total duration of the drug treatment and for 3 months after the last session of RT/CRT. Non-sterilized male partners of a female patient of childbearing potential must use male condom plus spermicide throughout this period.
  • Non-sterilized male patients who are not abstinent and intend to be sexually active with a female partner of childbearing potential must use a male condom plus spermicide from the time of screening throughout the total duration of the drug treatment and for 3 months after the last session of RT/CRT. Male patients should refrain from sperm donation throughout this period. Female partners (of childbearing potential) of male patients must also use a highly effective method of contraception throughout this period.
  • ------

Who cannot join

  • Participation in another clinical study with an investigational product during the last 4 weeks prior to durvalumab administration.
  • Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
  • Any unresolved toxicity NCI CTCAE, Version 5, Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria:
  • Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
  • Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
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  • Prior chemotherapy or radiation therapy for lung cancer.
  • Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of investigational product.
  • History of allogenic organ transplantation.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:
  • Patients with vitiligo or alopecia.
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement.
  • Any chronic skin condition that does not require systemic therapy.
  • Patients without active disease in the last 5 years.
  • Patients with celiac disease controlled by diet alone.
  • Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
  • History of another primary malignancy except for:
  • Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of investigational product and of low potential risk for recurrence.
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated carcinoma in situ without evidence of disease.
  • History of leptomeningeal carcinomatosis.
  • 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.
  • Current or prior use of immunosuppressive medication within 14 days before the administration of durvalumab. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection).
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent.
  • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  • Receipt of live attenuated vaccine within 30 days prior to durvalumab infusion. Note: Patients, if enrolled, should not receive live vaccine up to 30 days after durvalumab infusion.
  • Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 3 months after the last session of RT/CRT.
  • Known allergy or hypersensitivity to any of the study drugs or any of its excipients.
  • Prior randomization or treatment in a previous durvalumab clinical study regardless of treatment arm assignment.
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies.
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
  • Severe infections within 4 weeks prior to screening, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
  • Signs or symptoms of infection within 2 weeks prior to screening.
  • History of any hematological disease not considered in complete remission for at least 5 years before screening.
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
  • Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements.

Trial locations and contacts

1 site in 1 country.

Júlio Oliveira, MD contact

+351225084000 ext. 2042

earlytrials@ipoporto.min-saude.pt

Joana H Maia contact

+351225084000 ext. 2042

clinicalstudies@ipoporto.min-saude.pt

Portugal1 site, 1 recruiting

  • Instituto Português de Oncologia do Porto FG, EPE (IPO-Porto)

    Porto, 4200-072

    Julio Oliveira, MD, earlytrials@ipoporto.min-saude.pt

    Joana H Maia, PharmD, clinicalstudies@ipoporto.min-saude.pt

    Recruiting

Other trials in Portugal

About this study

This study proposes to evaluate the safety and efficacy of an anti-PD-L1 (durvalumab) agent as neoadjuvant therapy in patients diagnosed with localized NSCLC who are planned to undergo radical RT or CRT. The hypothesis to be tested for the primary objective is that the treatment of durvalumab followed by RT/CRT will be safe and well tolerated in subjects with NSCLC.

Read the detailed description

Targeting the PD1/PD-L1 pathway has demonstrated activity in patients with several advanced malignancies. Treatment with anti-PD1/PD-L1 blockade in advanced and, more recently, locally advanced NSCLC, is already standard of care. The positive outcomes of durvalumab following CRT emphasized the potential of immunotherapy integration in multimodality treatment strategies and in earlier phases of the disease, leading to the first immune checkpoint inhibitor approval in non-metastatic setting in NSCLC. Furthermore, growing evidence is pointing to the efficacy of neoadjuvant treatments in NSCLC. This study proposes to evaluate the safety and efficacy of an anti-PD-L1 (durvalumab) agent as neoadjuvant therapy in patients diagnosed with localized NSCLC who are planned to undergo radical RT or CRT.

The hypothesis to be tested for:

  • Primary objective: To evaluate the safety, as assessed by incidence of dose limiting toxicity (DLT), of durvalumab followed by RT/CRT in patients with early stage or locally advanced, unresectable NSCLC who are planned to undergo radical RT or CRT.
  • Secondary Objectives: To evaluate the safety, the efficacy and the feasibility of durvalumab followed by RT/CRT.
  • Exploratory Objectives: To assess the Quality of Life (QoL) using SF-36v2 and EQ-5D-5L and to assess blood and tumor tissue for potential biomarkers which predict and/or correlate with clinical outcomes.
Being tested
Durvalumab, standard of care RT/RCT
Keywords
Non-Small Cell Lung Cancer (NSCLC), PD1/PD-L1, anti-PD1/PD-L1 blockade, Non-Surgical Early Stage or Locally Advanced NSCLC
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.

  • DurvalumabDrug

    Patients will receive 1500 mg of durvalumab (MEDI4736) via IV infusion

  • standard of care RT/RCTOther

    standard of care RT/RCT

Study groups in NCT05267392
Study groupRoleWhat they receive
DurvalumabExperimentalAll subjects enrolled in the study will receive open-label neoadjuvant durvalumab 1500 mg followed by standard of care RT/RCT
Receives: Drug: Durvalumab; Other: standard of care RT/RCT

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Dose-Limiting Toxicity (DLT)

    Rate of patients without Dose-Limiting Toxicity (DLT) evaluated from durvalumab administration until 5 - 6 weeks after the last session of RT/CRT.

    Measured: Through study development up to 5 - 6 weeks after the last session of RT/CRT for each enrolled patient

Secondary outcomes (4)

  1. Safety of durvalumab followed by RT/CRT

    Presence of adverse events (AEs) assessed by (CTCAE) version 5.0

    Measured: Through study development up to 17 weeks for each enrolled patient

  2. objective response rate

    percentage of patients having a complete response or a partial response as measured by RECIST 1.1.

    Measured: Through study development up to 17 weeks for each enrolled patient

  3. Pathologic response rate

    Patients in whom tumor "downstaging" was achieved and making the patient eligible for surgery.

    Measured: Through study development up to 17 weeks for each enrolled patient

  4. feasibility of durvalumab followed by RT/CRT

    proportion of enrolled patients starting RT/CRT within 4 - 5 weeks after durvalumab administration and proportion of enrolled patients completing the clinical trial.

    Measured: Through study development up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Mar 2022
  2. Study start16 Feb 2021
  3. Primary completionJul 2023 (estimated)
  4. Study completionJan 2024 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05267392
Sponsor's protocol ID
ESR-18-13828
Other IDs
2019-002884-90, 2019
Acronym
IDEAR
Status last verified
Dec 2021
First submitted
13 Dec 2021
Last updated
4 Mar 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Durvalumab in people with Non-small Cell Lung Cancer, run by Instituto Portugues de Oncologia, Francisco Gentil, Porto at 1 site in Portugal.

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 27 inclusion and 38 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 4 Mar 2022. 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 Portugal. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 Júlio Oliveira, MD (+351225084000 ext. 2042, earlytrials@ipoporto.min-saude.pt), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Dose-Limiting Toxicity (DLT) (time frame: Through study development up to 5 - 6 weeks after the last session of RT/CRT for each enrolled patient). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05267392.

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 4 Mar 2022.

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