Clinical trial NCT04982549: A Study to Evaluate the Safety of Concurrent Durvalumab With CRT Followed by Durvalumab for Chinese Unresectable Stage III NSCLC
Official title: A Prospective Study to Evaluate the Safety of Concurrent Durvalumab (MEDI4736) With Chemoradiation Therapy（CRT）Followed by Durvalumab for Chinese Unresectable Stage III Non Small Cell Lung Cancer（NSCLC）
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Unresectable Stage III NSCLC
Lead sponsor: Shandong Cancer Hospital and Institute
Sponsor class: OTHER
First posted: 2021-07-29
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a prospective, multi-center, single arm study assessing the efficacy and safety of durvalumab given concurrently with platinum-based CRT (durvalumab + SoC CRT) in patients with locally advanced, unresectable NSCLC (Stage III).

Detailed description: Approximately 35 patients with locally advanced, unresectable NSCLC (Stage III) who are eligible to receive platinum-based CRT will be enrolled in and receive durvalumab + SoC CRT. Patients with CR, partial response (PR), or stable disease (SD）based on Investigator assessment at the 16-week tumor evaluation following completion of SoC CRT will continue to receive durvalumab as consolidation treatment. Patients with RECIST 1.1-defined radiological progressive disease (PD) will proceed to follow-up.

Eligibility criteria: Inclusion Criteria:

* Subjects with histologically or cytologically-documented NSCLC
* Locally advanced, unresectable (Stage III) NSCLC
* World Health Organization (WHO) performance status 0-1
* At least one measurable lesion, not previously irradiated
* Must have a life expectancy of at least 12 weeks at randomization
* Adequate lung function: Pre- or post-bronchodilator forced expiratory volume 1 of 1.0 L or \>40% predicted value and DLCO \>30% predicted value
* Must provide an archived tumor tissue block(or at least 15 newly cut unstained slides)≤3 years old; if archived sample unavailable then must provide a recent(≤3 months) tumor biopsy.

Exclusion Criteria:

* Mixed small-cell and NSCLC histology
* Receipt of prior or current cancer treatment, including but not limited to, radiation therapy, investigational agents, chemotherapy, Durvalumab and mAbs.
* Prior exposure to immune-mediated therapy, including but not limited to, other anti- CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies.
* Patients whose radiation treatment plans are likely to encompass a volume of whole lung receiving ≥20 Gy in total (V20) of more than 35% of lung volume
* Planned radiation cardiac dose V50\>25%
* Any medical contraindication of platinum-based doublet chemotherapy as listed in the local labelling or known allergy/hypersensitivity to investigational product and/or its excipients
* History of the following: allogeneic organ transplantation, active or prior autoimmune or inflammatory disorders, another primary malignancy, leptomeningeal carcinomatosis, active primary immunodeficiency
* Uncontrolled intercurrent illness or active infection

Primary outcomes:
measure: Grade ≥3 immune-mediated Adverse event
timeFrame: From the date of first dose until disease progression,assessed up to 4 years
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: From date of first dose until the date of objective disease progression or death,assessed up to 4 years
measure: Overall Survival (OS)
timeFrame: From the date of first dose until death due to any cause,assessed up to 4 years
measure: Objective response rate(ORR)
timeFrame: From the date of first dose until the date of objective disease progression or death,assessed up to 4 years
measure: Duration of response(DOR)
timeFrame: From the date of first documented response (RECIST 1.1.) until the first date of documented progression or death in the absence of disease progression,assessed up to 4 years
measure: Disease control rate(DCR)
timeFrame: From the date of first dose until 24 weeks.
measure: Time to death or distant metastasis(TTDM)
timeFrame: From the date of first dose to until the first date of distant metastasis or death in the absence of distant metastasis,assessed up to 4 years
Other outcomes:
measure: Adverse events
timeFrame: From the date of enrollment until disease progression,assessed up to 4 years
Locations:
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
Study officials:
References: