Clinical trial NCT03872661: Neoadjuvant IBI308, Bevacizumab, Plus Pemetrexed and Carboplatin Followed by Surgery in Unresectable Stage III NSCLC
Official title: A Multicenter Phase II Trial of Neoadjuvant IBI308, Bevacizumab, Plus Pemetrexed and Carboplatin Followed by Surgery in Patients With Unresectable Stage III Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Lung Cancer Stage III
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2019-03-13
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to studying neoadjuvant IBI308, bevacizumab, plus pemetrexed and carboplatin followed by surgery to see how well it works in treating patients with unresectable stage III non-small cell lung cancer.

Detailed description: Concurrent chemoradiotherapy is the recommended therapeutic approach for patients with unresectable stage III non-small cell lung cancer (NSCLC), although surgery offers the chance of cure. With combined-modality therapy with radiation therapy and chemotherapy, the prognosis of stage III NSCLC remains poor. IBI308 (sintilimab) is a recombinant humanized anti-PD-1 monoclonal antibody. This study is to studying neoadjuvant IBI308, bevacizumab, plus pemetrexed and carboplatin followed by surgery to see how well it works in treating patients with unresectable stage III non-small cell lung cancer.

Eligibility criteria: Inclusion Criteria:

* Target population is unresectable stage III non-small cell lung cancer.
* Written informed consent provided.
* Subjects should not have a previously detected sensitizing EGFR mutation or ALK fusion oncogene.
* Male and female patients aged ≥18 years, \< 75 years.
* Able to comply with the required protocol and follow-up procedures, and able to receive oral medications.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
* Life expectancy ≥12 weeks.
* Adequate hematological function: Absolute neutrophil count (ANC) ≥2.0 x 109/L, and Platelet count ≥100 x 109/L, and Hemoglobin ≥9 g/dL (may be transfused to maintain or exceed this level).
* Adequate liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN), Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x ULN in subjects without liver metastases; ≤ 5 x ULN in subjects with liver metastases.
* Adequate renal function: Serum creatinine ≤ 1.25 x ULN, or ≥ 60 ml/min.
* Female subjects should not be pregnant or breast-feeding.

Exclusion Criteria:

* Known severe hypersensitivity to IBI308 or any of the excipients of this product.
* Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody (including any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
* Prior chemotherapy or radiotherapy.
* Subjects with active, known or suspected autoimmune disease. Subjects in conditions not expected to recur in the absence of an external trigger, or not requiring systemic treatment are permitted to enroll.
* Subjects with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first administration of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
* Inability to comply with protocol or study procedures.
* A serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study.
* A serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease.
* History of another malignancy in the last 5 years with the exception of the following: other malignancies cured by surgery alone and having a continuous disease-free interval of 5 years are permitted. Cured basal cell carcinoma of the skin and cured in situ carcinoma of the uterine cervix are permitted.
* Any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease).
* Patient who has active serious infection (e.g. pyrexia of or 38.0℃ over)
* Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
* Known history of active Hepatitis B or C.
* Women who are pregnant or nursing.
* Evidence of any other disease, neurological or metabolic dysfunction, physical examination or laboratory finding giving reasonable suspicion of a disease or condition that contraindicated the use of an investigational drug or puts the subject at high risk for treatment-related complications.

Primary outcomes:
measure: Resectability rate
timeFrame: 3 months
Secondary outcomes:
measure: Number of participants with perioperative complications
timeFrame: 2 years
Other outcomes:
measure: Event-free survival
timeFrame: 2 years
measure: Overall survival
timeFrame: 2 years
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
References: