A Study to Determine Safety of Durvalumab After Sequential Chemo Radiation in Patients With Unresectable Stage III Non-Small Cell Lung Cancer

Completed · Phase 2

Conditions studied: Non-small Cell Lung Cancer (NSCLC)

In brief

This is a Phase II, open-label, multi-centre study to determine the safety of a fixed dose of Durvalumab (MEDI4736) (1500 mg) every 4 weeks \[q4w\] in participants with unresectable Stage III Non-Small Cell Lung Cancer (NSCLC), who have not progressed following platinum-based sequential chemoradiation therapy (sCRT). This study will be conducted in Europe and North America.

Key facts

Study ID

NCT03693300

Run by

AstraZeneca

People needed

117

Starts

2019-04-16

Expected to finish

2023-04-21

Last updated by the study team

2024-06-18

Who can join

Age: 18 and older, up to 130. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
• Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses.
• Provision of signed and dated written genetic informed consent prior to collection of sample for genetic analysis (optional).
• 18 years or older at the time of signing the ICF.
• Histologically- or cytologically-documented NSCLC with locally-advanced, unresectable Stage III disease (according to the IASLC Staging Manual Version 8 [IASLC 2016]). Positron emission tomography (PET)/CT, MRI of the brain, and endobronchial ultrasound with biopsy are highly encouraged at diagnosis.
• Receipt of sCRT which must have been completed within 42 days prior to first IP dose administration in the study.
• The platinum-based chemotherapy regimen must contain cisplatin or carboplatin and 1 of the following agents: etoposide, vinblastine, vinorelbine, a taxane (paclitaxel or docetaxel), or pemetrexed, according to the local standard of care (SoC) regimens. Platinum-based chemotherapy containing cisplatin or carboplatin and gemcitabine is permitted under certain conditions - refer to bullet point 6(b).
• Patients must have received at least 2 cycles of platinum-based chemotherapy before radiation therapy. The interval between administration of the last dose of chemotherapy regimen and start of radiation therapy must be no more than 6 weeks. Consolidation chemotherapy after radiation is not permitted.
• (i) If the patient's platinum-based chemotherapy contained gemcitabine, no overlap between chemotherapy and radiation therapy is permitted.
• (ii) If the patient's platinum-based chemotherapy contained any of the agents listed in (a) other than gemcitabine, an overlap of 1 cycle of chemotherapy and radiation therapy is acceptable.
• (c) Patients must have received a total dose of radiation of 60 Gy ±10% (54 Gy to 66 Gy). Sites are encouraged to adhere to mean organ radiation dosing as follows: (i) Mean lung dose <20 Gy and/or V20 <35%; (ii) Mean oesophagus <34 Gy; (iii) Heart V45 <35% or V30 <30%. Note: Sites should be aware of the recent RTOG 0617 Study data demonstrating that doses higher than 60 Gy may be associated with greater toxicity and worse efficacy.
• (d) Patients with WHO/ECOG PS 2 or chronic lung disease (pulmonary emphysema or chronic obstructive pulmonary disease) must have received a V20 <25%.
• Patients must not have progressed following platinum-based sCRT, as per Investigator assessed RECIST 1.1 criteria. . In order to assess disease progression, the baseline imaging (CT/MRI) used for Screening purposes should be compared against the most recently performed scan that allows physician assessment as per RECIST 1.1 criteria. If an intermediate scan taken between chemotherapy and radiotherapy is available and that scan is suitable for physician assessment as per RECIST 1.1 criteria, then this scan should be used.
• Patients with measurable disease and/or non-measurable and/or no evidence of disease (NED) assessed at baseline by CT/MRI will be entered in this study.
• Prior irradiated lesions may be considered measurable and selected as TLs provided they fulfil the other criteria for measurability.
• Must have a life expectancy of at least 12 weeks at enrolment.
• WHO/ECOG PS ≤2.
• Adequate organ and marrow function at enrolment as defined below. These parameters should be achieved without augmentation by growth factors, transfusions, or infusions within 14 days of screening unless required for SoC:
• Haemoglobin ≥9.0 g/dL;
• Absolute neutrophil count >1.0 × 109/L;
• Platelet count >75 × 109/L;
• Serum bilirubin ≤1.5 × upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome, who will be allowed in consultation with their physician.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN.
• Measured creatinine clearance >40 mL/min or calculated creatinine clearance >40 mL/min as determined by Cockcroft-Gault (using actual body weight) (Cockcroft and Gault 1976).
• Males:

You may not qualify if…

• Patients with locally-advanced NSCLC whose disease has progressed following platinum based sCRT.
• Patients who have disease considered for surgical treatment as part of their care plan, such as Pancoast or superior sulcus tumours.
• Mixed small-cell lung cancer and NSCLC histology.
• History of allogeneic organ transplantation.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, 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 (eg, 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 at enrolment may be included but only after consultation with the Study Physician.
• 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, ILD, serious chronic GI conditions associated with diarrhoea, 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 IP 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 tuberculosis testing in line with local practice), hepatitis B (known positive hepatitis B surface antigen [HbsAg] result), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies). Patients with a past or resolved hepatitis B virus (HBV) infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HbsAg) are eligible. Patients positive for hepatitis C antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA).
• Any unresolved toxicity of NCI CTCAE 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 or Grade ≥2 lymphopenia 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 (MEDI4736) may be included only after consultation with the Study Physician.
• Known allergy or hypersensitivity to durvalumab (MEDI4736) or any of the IP excipients.
• Patients who have received cCRT for locally-advanced NSCLC, or who received sCRT with at least 2 concomitant CRT cycles. Prior surgical resection (ie, Stage I or II) is permitted.
• Note: Patients whose platinum-based chemotherapy contained gemcitabine and who received sCRT with at least 1 concomitant CRT cycle are excluded from this study.
• Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.

Where it is running

• Research Site — Gainesville, Georgia, United States
• Research Site — Knoxville, Tennessee, United States
• Research Site — Créteil, France
• Research Site — Paris, France
• Research Site — Saint-Priest-en-Jarez, France
• Research Site — Toulouse, France
• Research Site — Gauting, Germany
• Research Site — Großhansdorf, Germany
• Research Site — Hamm, Germany
• Research Site — Hanover, Germany
• Research Site — Heidelberg, Germany
• Research Site — Avellino, Italy
• Research Site — Meldola, Italy
• Research Site — Milan, Italy
• Research Site — Monza, Italy
• Research Site — Parma, Italy
• Research Site — Roma, Italy
• Research Site — Barcelona, Spain
• Research Site — Guadalajara, Spain
• Research Site — Madrid, Spain
• Research Site — Seville, Spain
• Research Site — Valencia, Spain
• Research Site — Leeds, United Kingdom
• Research Site — Manchester, United Kingdom
• Research Site — Middlesbrough, United Kingdom

Full record on ClinicalTrials.gov

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