Concurrent Neoadjuvant Chemoradiotherapy Plus Durvalumab (MEDI4736) in Resectable Stage III NSCLC

NCT03694236 | Recruiting Phase 1

• 1 other identifier: 4-2018-0353
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

Combination treatment of Durvalumab with chemoradiotherapy is ongoing for head/neck cancer, renal cell carcinoma, melanoma, and non-small cell lung cancer (NCT02318771) and pancreatic cancer (NCT02305186).Combining Durvalumab with neoadjuvant chemoradiotherapy is a promising strategy to improve clinical outcome in stage III lung cancer. Using serial biopsied and surgically resected fresh tissue through the novel/high-throughput RNA sequencing technologies, we want to identify the change immune signature in tumor microenvironment of NSCLC patients after Durvalumab treatment. With hypothesis that PD-1 inhibitor as a component of neoadjuvant chemoradiotherapy followed by surgery could increase complete pathologic response rate and disease free survival, and overall survival, we suggest adding Durvalumab to neoadjuvant chemoradiation in stage II/III resectable NSCLC. And with immune marker study using FACS, whole exome sequencing, or RNAsequencing, we can find the potential predictive biomarker for anti-PD-L1 blockade. And in this study, we can get "whole" surgical specimen not biopsy sample after Durvalumab treatment so the analysis for immune marker, tumor microenvironment, and various tumor infiltrating immune cells and their changes will be available.

Conditions

Potentially Resectable Stage II/IIIa NSCLC

Keywords

NSCLC; Durvalumab; medi4736

Outcome Measures

Primary Outcomes (1)

• pathologic complete response (pCR) rate

  To evaluate pathologic complete response (pCR) rate

  for 6 weeks

Secondary Outcomes (4)

• Objective response rate (ORR)

  from date of randomization until the date of first documented progression, assessed up to 5 years

• DFS (disease free survival)

  from date of randomization until the date of first documented progression, assessed up to 5 years

• OS (overall survival)

  from date of randomization until the date of first documented progression, assessed up to 5 years

• clinical and pathologic down staging rate

  from date of randomization until the date of first documented progression, assessed up to 5 years

Study Arms (1)

durvalumab

EXPERIMENTAL

This study is single arm phase II study to evaluate efficacy and safety of durvalumab and chemoradiotherapy (paclitaxel and carboplatin) in treatment-naïve clinical stage II/IIIa NSCLC.

Drug: durvalumab

Interventions

durvalumab DRUG

Neo-adjuvant chemoradiation period The treatment consisted of paclitaxel, carboplatin, duvalumab and radiation. The radiation treatment comprises 45Gy (total 25Fr) and that will be about 5 weeks. Intensity modulated RT (IMRT) or 3D CRT (three-dimensional conformal radiotherapy) will be allowed. Surgery Chest CT and/or PET CT with appropriate other diagnostic method (ex. Bronchoscopy) will be performed before surgery and type of surgery Follow-up period There is every 4 month visit with chest CT and abdominal CT is done at 1,2,5 post-op year. Other diagnostic method can be performed if indicated.

durvalumab

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed NSCLC
• Clinical stage III (including N2 stage and potential candidate for resection)
• Written informed consent and any locally-required authorization (IRB) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
• Age \> 20 years at time of study entry
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate normal organ and marrow function as defined below:
• Haemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1,500μL
• Platelet count ≥ 100,000μL
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). \<This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.\>\>
• AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN
• Serum 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:
• Males:
• Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)
• Females: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL) 6. Life expectancy of 6 months 8. Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: ≥50 years old and no menses for 1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.

You may not qualify if:

• Patients with metastatic lesions or clinical N3 lymph nodes
• Participation in another clinical study with an investigational product during the last 60 months
• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) Previous enrollment in the present study
• Any previous treatment (chemotherapy, radiotherapy or surgery) to current disease - NSCLC
• Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
• History of leptomeningeal carcinomatosis
• Brain metastases or spinal cord compression. Subjects with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry
• Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤ 36months prior to the first dose of study drug
• Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
• Current or prior use of immunosuppressive medication within 14days (use 28 days if combining durvalumab with a novel agent) before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (eg, 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 (eg, chemotherapy, CT scan premedication)
• Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable.

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Severance Hospital

Seoul, 03722, South Korea

RECRUITING

MeSH Terms

Interventions

durvalumab

Central Study Contacts

Byoung Chul Cho, MD

CONTACT

82 2 2228 088; cbc1971@yuhs.ac

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2018
• First Posted: October 3, 2018
• Study Start: February 12, 2019
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: September 26, 2019

Record last verified: 2019-09

Locations

KR (1)