Back to resultsClinical Trial for Evaluating Efficacy and Safety of PDR001 in Concurrent Plus Consolidation Versus Consolidation Only in Addition to Standard Chemoradiotherapy in Unresectable Stage III NSCLC Patients (PASTURE)
Primary Purpose
Stage III NSCLC
Status
Withdrawn
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
standard platinum-based concurrent chemoradiotherapy, followed by consolidation with PDR001
PDR001 concurrent with standard platinum-based chemoradiation, followed by consolidation with PDR001
Sponsored by
About this trial
This is an interventional treatment trial for Stage III NSCLC focused on measuring Non small cell lung cancer, Unresectable stage III NSCLC
Eligibility Criteria
Inclusion Criteria:
- Patients with cytologically or histologically proven, locally advanced, treatment-naïve, unresectable, both squamous and non-squamous stage III NSCLC* (According to AJCC TNM staging 8th edition, IIIB and IIIC diseases are eligible; Inoperable stage IIIA disease without any exclusion criteria is also eligible)
- Patients with targetable mutations such as EGFR, ALK and ROS1 are also eligible
- Measurable disease based on RECIST 1.1 as determined by the site.
- Men and women ≥ 20 years of age
- A performance status of 0 - 1 on the Eastern Cooperative Oncology Group (ECOG) performance Status
Adequate hematologic, renal, and hepatic function as follows:
- Absolute Neutrophil Count (ANC), > 1,000/mm3
- Platelets > 100,000/mm3
- Hemoglobin > 9.0 g/dL
- Serum creatinine < 1.5 × upper normal limit (ULN) OR creatinine clearance > 45 mL/min/1.73m2
- AST and/or ALT < 2.5 × the ULN
- Bilirubin < 1.5 × the ULN
- 12-Lead electrocardiogram (ECG) shows QTc interval ≤470 msec and without history of Torsades de Pointes or other symptomatic QTc abnormality
- Written (signed) Informed Consent to participate in the study
Exclusion Criteria:
- Prior exposure to any anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associate antigen-4 (CTLA-4) antibody
- Active or prior autoimmune disease or history of immunodeficiency
- Current or prior use of immunosuppressive agents within 28 days before the first dose of investigational drugs, with the exception of intranasal, inhaled, or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
- Use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GMCSF, M-CSF), thrombopoietin mimetics or erythroid stimulating agents ≤ 2 weeks prior start of study treatment. If erythroid stimulating agents were initiated more than 2 weeks prior to the first dose of study treatment and the patient is on a stable dose, they can be maintained
- Experience of solid organ transplant
- Evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses or active infections including hepatitis B, C and HIV.
- Evidence of uncontrolled illness such as symptomatic congestive heart failure, uncontrolled hypertension or unstable angina pectoris.
- Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis)
- Active infection of lung, including pulmonary tuberculosis, pneumonia
- Has a history of interstitial lung disease (ILD) or a history of pneumonitis that has required oral or IV steroids.
- Pregnant female subject (Female subjects must have a negative urine or serum pregnancy test at screening if of childbearing potential, or be of non-child bearing potential.)
- Lactating female subject
- Prior malignancy, with the exception of basal cell/ squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or has undergone potentially curative therapy with no evidence of that disease recurrence for 3 years since initiation of that therapy
Sites / Locations
- Department of Oncology, Yonsei University College of Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Arm A (consolidation only arm)
Arm B (concurrent arm)
Arm Description
Arm A (consolidation only arm) will be treated with standard platinum-based concurrent chemoradiotherapy, followed by consolidation with PDR001 regimen. --For concurrent chemoradiation therapy, chemotherapeutic agents will follow the one of the two regimens of standard of care Paclitaxel 45 mg/m2 at D1, D8, D15, D22, D29, and D36, IV infusion; Carboplatin AUC 2 at D1, D8, D15, D22, D29, and D36, IV infusion Etoposide 50 mg/m2 D1-5, D29-33,IV infusion; Cisplatin 50 mg/m2 D1, D8, D29, and D36; IV infusion - Concurrent radiation therapy (generally, 60 Gy/30 Fx ±10%) - Consolidation therapy: after 2 weeks after completion of radiation therapy (± 7 days), PDR001 400 mg every 4 weeks, until disease progression or an unacceptable adverse event, maximum 12 months.
Arm B (concurrent arm) will be treated with PDR001 concurrent with standard platinum-based chemoradiation, followed by consolidation with PDR001 regimen. --For concurrent chemoradiation therapy, chemotherapeutic agents will follow one of the two regimens of standard of care Paclitaxel 45 mg/m2 at D1, D8, D15, D22, D29, and D36, IV infusion; Carboplatin AUC 2 at D1, D8, D15, D22, D29, and D36, IV infusion Etoposide 50 mg/m2 D1-5, D29-33,IV infusion; Cisplatin 50 mg/m2 days 1,8,29, and 36; IV infusion - Concurrent PDR001 400mg at D1, D29 - Concurrent radiation therapy (generally, 60 Gy/30 Fx ±10%) - Consolidation therapy: after 4 weeks after last dose of PDR001, PDR001 400 mg every 4 weeks, until disease progression or an unacceptable adverse event, maximum 12 months.
Outcomes
Primary Outcome Measures
Progression Free survival (PFS)
To compare the progression free survival (PFS) in concurrent plus consolidation PDR001 vs. consolidation PDR001 only in addition to standard platinum-based concurrent chemoradiation, in the patients with locally advanced, unresectable stage III NSCLC.
Secondary Outcome Measures
To evaluate antitumor efficacy of PDR001: OS
To evaluate the overall survival (OS) of PDR001 as concurrent plus consolidation versus consolidation only treatment in addition to platinum-based concurrent chemoradiation, in the patients with locally advanced, unresectable stage III NSCLC.
To evaluate antitumor efficacy of PDR001: ORR
To compare objective response rate (ORR; evaluated by RECIST) of the patients who received platinum-based concurrent chemoradiation with or without concurrent PDR001.
Incidence of Treatment-Emergent Adverse Events[Safety and Tolerability)
To evaluate the safety and tolerability profile of PDR001 as concurrent plus consolidation versus consolidation only treatment in addition to platinum-based concurrent chemoradiation.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03945227
Brief Title
Clinical Trial for Evaluating Efficacy and Safety of PDR001 in Concurrent Plus Consolidation Versus Consolidation Only in Addition to Standard Chemoradiotherapy in Unresectable Stage III NSCLC Patients (PASTURE)
Official Title
A Phase II Clinical Trial for Evaluating Efficacy and Safety of PDR001 in Concurrent Plus Consolidation Versus Consolidation Only in Addition to Standard Chemoradiotherapy in Unresectable Stage III NSCLC Patients (PASTURE)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Due to the delay in the study shceduled, due to the start of competitive study and the approval of Durvalumab from the Ministry of Food and Drug Safety, it was judged that it was difficult to enroll subjects.
Study Start Date
June 2019 (Anticipated)
Primary Completion Date
January 2022 (Anticipated)
Study Completion Date
January 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yonsei University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a multi-center, open-label, randomized Phase 2 trial evaluating PDR001 in two arms for concurrent chemoradiation and consolidation in the treatment-naïve patients with locally advanced, unresectable stage III NSCLC. Patients will be randomized in a 1:1 ratio (arm A and arm B):
Arm A (consolidation only arm) will be treated with standard platinum-based concurrent chemoradiotherapy, followed by consolidation with PDR001 regimen.
Arm B (concurrent arm) will be treated with PDR001 concurrent with standard platinum-based chemoradiation, followed by consolidation with PDR001 regimen.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage III NSCLC
Keywords
Non small cell lung cancer, Unresectable stage III NSCLC
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A (consolidation only arm)
Arm Type
Placebo Comparator
Arm Description
Arm A (consolidation only arm) will be treated with standard platinum-based concurrent chemoradiotherapy, followed by consolidation with PDR001 regimen. --For concurrent chemoradiation therapy, chemotherapeutic agents will follow the one of the two regimens of standard of care Paclitaxel 45 mg/m2 at D1, D8, D15, D22, D29, and D36, IV infusion; Carboplatin AUC 2 at D1, D8, D15, D22, D29, and D36, IV infusion Etoposide 50 mg/m2 D1-5, D29-33,IV infusion; Cisplatin 50 mg/m2 D1, D8, D29, and D36; IV infusion - Concurrent radiation therapy (generally, 60 Gy/30 Fx ±10%) - Consolidation therapy: after 2 weeks after completion of radiation therapy (± 7 days), PDR001 400 mg every 4 weeks, until disease progression or an unacceptable adverse event, maximum 12 months.
Arm Title
Arm B (concurrent arm)
Arm Type
Experimental
Arm Description
Arm B (concurrent arm) will be treated with PDR001 concurrent with standard platinum-based chemoradiation, followed by consolidation with PDR001 regimen. --For concurrent chemoradiation therapy, chemotherapeutic agents will follow one of the two regimens of standard of care Paclitaxel 45 mg/m2 at D1, D8, D15, D22, D29, and D36, IV infusion; Carboplatin AUC 2 at D1, D8, D15, D22, D29, and D36, IV infusion Etoposide 50 mg/m2 D1-5, D29-33,IV infusion; Cisplatin 50 mg/m2 days 1,8,29, and 36; IV infusion - Concurrent PDR001 400mg at D1, D29 - Concurrent radiation therapy (generally, 60 Gy/30 Fx ±10%) - Consolidation therapy: after 4 weeks after last dose of PDR001, PDR001 400 mg every 4 weeks, until disease progression or an unacceptable adverse event, maximum 12 months.
Intervention Type
Drug
Intervention Name(s)
standard platinum-based concurrent chemoradiotherapy, followed by consolidation with PDR001
Intervention Description
drug: standard platinum-based concurrent chemoradiotherapy, followed by consolidation with PDR001 Arm A (consolidation only arm) will be treated with standard platinum-based concurrent chemoradiotherapy, followed by consolidation with PDR001 regimen. --For concurrent chemoradiation therapy, chemotherapeutic agents will follow the one of the two regimens of standard of care Paclitaxel 45 mg/m2 at D1, D8, D15, D22, D29, and D36, IV infusion; Carboplatin AUC 2 at D1, D8, D15, D22, D29, and D36, IV infusion Etoposide 50 mg/m2 D1-5, D29-33,IV infusion; Cisplatin 50 mg/m2 D1, D8, D29, and D36; IV infusion - Concurrent radiation therapy (generally, 60 Gy/30 Fx ±10%) - Consolidation therapy: after 2 weeks after completion of radiation therapy (± 7 days), PDR001 400 mg every 4 weeks, until disease progression or an unacceptable adverse event, maximum 12 months.
Intervention Type
Drug
Intervention Name(s)
PDR001 concurrent with standard platinum-based chemoradiation, followed by consolidation with PDR001
Intervention Description
drug:PDR001 concurrent with standard platinum-based chemoradiation, followed by consolidation with PDR001 Arm B (concurrent arm) will be treated with PDR001 concurrent with standard platinum-based chemoradiation, followed by consolidation with PDR001 regimen. -For concurrent chemoradiation therapy, chemotherapeutic agents will follow one of the two regimens of standard of care Paclitaxel 45 mg/m2 at D1, D8, D15, D22, D29, and D36, IV infusion; Carboplatin AUC 2 at D1, D8, D15, D22, D29, and D36, IV infusion Etoposide 50 mg/m2 D1-5, D29-33,IV infusion; Cisplatin 50 mg/m2 days 1,8,29, and 36; IV infusion - Concurrent PDR001 400mg at D1, D29 - Concurrent radiation therapy (generally, 60 Gy/30 Fx ±10%) - Consolidation therapy: after 4 weeks after last dose of PDR001, PDR001 400 mg every 4 weeks, until disease progression or an unacceptable adverse event, maximum 12 months.
Primary Outcome Measure Information:
Title
Progression Free survival (PFS)
Description
To compare the progression free survival (PFS) in concurrent plus consolidation PDR001 vs. consolidation PDR001 only in addition to standard platinum-based concurrent chemoradiation, in the patients with locally advanced, unresectable stage III NSCLC.
Time Frame
Repeated tumor imaging will be performed every 8 weeks from randomization until the date of disease progression or up to 18 months. And Tumor Imaging Change will assessed by RECIST 1.1
Secondary Outcome Measure Information:
Title
To evaluate antitumor efficacy of PDR001: OS
Description
To evaluate the overall survival (OS) of PDR001 as concurrent plus consolidation versus consolidation only treatment in addition to platinum-based concurrent chemoradiation, in the patients with locally advanced, unresectable stage III NSCLC.
Time Frame
Repeated tumor imaging will be performed every 8 weeks from randomization until the date of disease progression or up to 18 months. And Tumor Imaging Change will assessed by RECIST 1.1
Title
To evaluate antitumor efficacy of PDR001: ORR
Description
To compare objective response rate (ORR; evaluated by RECIST) of the patients who received platinum-based concurrent chemoradiation with or without concurrent PDR001.
Time Frame
Repeated tumor imaging will be performed every 8 weeks from randomization until the date of disease progression or up to 18 months. And Tumor Imaging Change will assessed by RECIST 1.1
Title
Incidence of Treatment-Emergent Adverse Events[Safety and Tolerability)
Description
To evaluate the safety and tolerability profile of PDR001 as concurrent plus consolidation versus consolidation only treatment in addition to platinum-based concurrent chemoradiation.
Time Frame
Repeated tumor imaging will be performed every 8 weeks from randomization until the date of disease progression or up to 18 months. And Tumor Imaging Change will assessed by RECIST 1.1
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with cytologically or histologically proven, locally advanced, treatment-naïve, unresectable, both squamous and non-squamous stage III NSCLC* (According to AJCC TNM staging 8th edition, IIIB and IIIC diseases are eligible; Inoperable stage IIIA disease without any exclusion criteria is also eligible)
Patients with targetable mutations such as EGFR, ALK and ROS1 are also eligible
Measurable disease based on RECIST 1.1 as determined by the site.
Men and women ≥ 20 years of age
A performance status of 0 - 1 on the Eastern Cooperative Oncology Group (ECOG) performance Status
Adequate hematologic, renal, and hepatic function as follows:
Absolute Neutrophil Count (ANC), > 1,000/mm3
Platelets > 100,000/mm3
Hemoglobin > 9.0 g/dL
Serum creatinine < 1.5 × upper normal limit (ULN) OR creatinine clearance > 45 mL/min/1.73m2
AST and/or ALT < 2.5 × the ULN
Bilirubin < 1.5 × the ULN
12-Lead electrocardiogram (ECG) shows QTc interval ≤470 msec and without history of Torsades de Pointes or other symptomatic QTc abnormality
Written (signed) Informed Consent to participate in the study
Exclusion Criteria:
Prior exposure to any anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associate antigen-4 (CTLA-4) antibody
Active or prior autoimmune disease or history of immunodeficiency
Current or prior use of immunosuppressive agents within 28 days before the first dose of investigational drugs, with the exception of intranasal, inhaled, or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
Use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GMCSF, M-CSF), thrombopoietin mimetics or erythroid stimulating agents ≤ 2 weeks prior start of study treatment. If erythroid stimulating agents were initiated more than 2 weeks prior to the first dose of study treatment and the patient is on a stable dose, they can be maintained
Experience of solid organ transplant
Evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses or active infections including hepatitis B, C and HIV.
Evidence of uncontrolled illness such as symptomatic congestive heart failure, uncontrolled hypertension or unstable angina pectoris.
Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis)
Active infection of lung, including pulmonary tuberculosis, pneumonia
Has a history of interstitial lung disease (ILD) or a history of pneumonitis that has required oral or IV steroids.
Pregnant female subject (Female subjects must have a negative urine or serum pregnancy test at screening if of childbearing potential, or be of non-child bearing potential.)
Lactating female subject
Prior malignancy, with the exception of basal cell/ squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or has undergone potentially curative therapy with no evidence of that disease recurrence for 3 years since initiation of that therapy
Facility Information:
Facility Name
Department of Oncology, Yonsei University College of Medicine
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
12. IPD Sharing Statement
Learn more about this trial
Clinical Trial for Evaluating Efficacy and Safety of PDR001 in Concurrent Plus Consolidation Versus Consolidation Only in Addition to Standard Chemoradiotherapy in Unresectable Stage III NSCLC Patients (PASTURE)
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