Cellular Immunotherapy Synergize Chemotherapy in Patients With Stage IV NSCLC
Primary Purpose
Non Small Cell Lung Cancer
Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
chemotherapy followed dendritic cells
pemetrexed and carboplatin
Sponsored by
About this trial
This is an interventional treatment trial for Non Small Cell Lung Cancer focused on measuring Lung Cancer, Chemotherapy, Immunotherapy
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed stage IV, non-squamous, wild-type EGFR,ALK-negative NSCLC
- Signed ICF and ability to comply with this protocol
- 18 years of age or older
- ECOG performance status of 0-1
- Patients must have measurable disease as defined by RECIST v. 1.1
- Systematic treatment naive with respect to the currently diagnosed NSCLC
- Patients must have recovered from toxicity of previous therapy. Recovery is defined as less than or equal to grade 2 toxicity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (except alopecia).
Sufficient hematologic and organ function for leukapheresis and chemotherapy:
- WBC equal to or higher than 4×10^9 /L
- Neutrophil equal to or higher than 1.5×10^9 /L
- PLT equal to or higher than 100×10^9 /L
- Hemoglobin equal to or higher than9 g/dL (90 g/L)
- Total bilirubin less than or equal to 1.5 times upper limit of normal (benign hereditary hyperbilirubinemias, eg, Gilbert's syndrome are permitted)
- Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) should be less than or equal to 3 times upper limit of normal. ALP, AST, and ALT less than or equal to 5 times upper limit of normal is acceptable if liver has tumor involvement.
- Creatinine clearance equal to or higher than 45 mL/min (calculated with the standard Cockcroft and Gault formula)
- Women of childbearing potential and sexually active males must agree to use an accepted and effective method of contraception (hormonal or barrier methods, abstinence) prior to study entry and for the duration of the treatment plus 3 months
Exclusion Criteria:
- Known active/untreated CNS metastases
- Any known primary immunodeficiency
- Any preexisting medical condition requiring long term chronic steroid or immunosuppressive therapy
- HIV positivity, hepatitis B and/or C infection, syphilis
- Past or current history of malignant neoplasm other than lung carcinoma, except for adequately treated non-melanoma skin cancer, in situ carcinoma of the cervix, or other cancer curatively treated and with no evidence of disease for at least five years
Patient's significant co-morbidities:
- Cardiovascular diseases - unstable angina pectoris, uncontrolled hypertension, myocardial infarction or ventricular arrhythmia or stroke within a 6-month period before randomization, congestive heart failure or cardiac arrhythmia not controlled by treatment
- Active severe infections or other severe medical condition
- Participation in a clinical study using experimental therapy and immunotherapy,monoclonal antibodies within the last 4 weeks prior to study entry
- Pregnant or breastfeeding woman
- History of severe hypersensitivity to pemetrexed and carboplatin and their ingredients, and to DCVAC ingredients
Sites / Locations
- Shanghai Chest HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
chemotherapy followed dendritic cells
chemotherapy
Arm Description
pemetrexed and carboplatin chemotherapy followed dendritic cells infusion from Cycle 3
pemetrexed and carboplatin chemotherapy only
Outcomes
Primary Outcome Measures
Progression-free survival
randomization to the date of an event defined as the first progression or death due to any cause (institution of a new systemic anticancer treatment will also be considered as a progression event),whichever occurs first up to 24 months
Secondary Outcome Measures
Safety parameters in terms of AE, laboratory abnormalities, and vital signs
adverse events [AEs], serious adverse events [SAEs], adverse events of special interest [AESIs], laboratory abnormalities, and vital signs
Overall Survival
Objective Response Rate
Full Information
NCT ID
NCT02669719
First Posted
January 11, 2016
Last Updated
January 28, 2016
Sponsor
Shanghai Chest Hospital
Collaborators
SOTIO a.s.
1. Study Identification
Unique Protocol Identification Number
NCT02669719
Brief Title
Cellular Immunotherapy Synergize Chemotherapy in Patients With Stage IV NSCLC
Official Title
A Randomized Phase II Study to Evaluate Efficacy and Safety of DCVAC/LuCa Added to Chemotherapy With Carboplatin and Pemetrexed vs Chemotherapy Alone in Patients With Stage IV Non-small Cell Lung Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
January 2016
Overall Recruitment Status
Unknown status
Study Start Date
January 2016 (undefined)
Primary Completion Date
January 2017 (Anticipated)
Study Completion Date
January 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Chest Hospital
Collaborators
SOTIO a.s.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a randomized, open-label, phaseⅡ study evaluating efficacy and safety of DC (dendritic cells) vaccine concurrent with chemotherapy compared to chemotherapy alone in patients with stage IV NSCLC (non small cell lung cancer) with wild-type EGFR (epidermal growth factor receptor).
Detailed Description
Screening period: Patients will be screened for eligibility for the clinical study within a 4-week period.
Randomization and leukapheresis periods: When the patients meet all entry criteria, they will be randomized in a ratio of 1:1 into one of the following two groups:
Group A (experimental group): Treatment with DC in addition to chemotherapy with 4-6 cycles of pemetrexed/carboplatin as first-line induction chemotherapy followed by pemetrexed as maintenance therapy. These patients will undergo leukapheresis within 1 week after randomization before start of treatment.
Group B (control group): Chemotherapy with 4-6 cycles of pemetrexed/carboplatin as first-line induction chemotherapy followed by pemetrexed as maintenance therapy.
Treatment periods:
Standard of care chemotherapy will be administered to patients in both treatment groups in cycles. Each chemotherapy cycle will be 3 weeks long. Patients in the group A will start with chemotherapy 2-5 days after leukapheresis, and patients in the group B will start with chemotherapy within 2 weeks after randomization.
Induction chemotherapy period
Pemetrexed in combination with carboplatin will be administered on Day 1 of each 3-week chemotherapy cycle. After 2 cycles of chemotherapy, tumor response will be evaluated according to RECIST v. 1.1. Patients with progressive disease or intolerance to chemotherapy will terminate study treatment but will be followed for survival. Patients with complete response, partial response, or stable disease will continue chemotherapy with carboplatin and pemetrexed for a total of 6 cycles . After at least a total of 4 cycles of chemotherapy, patients can be administered pemetrexed maintenance chemotherapy.
Maintenance chemotherapy period
During the Maintenance chemotherapy period, patients will receive pemetrexed of each 3-week chemotherapy cycle. Chemotherapy with pemetrexed will be administered in up to a total of 21 cycles or until disease progression or development of intolerance.
DCVAC
Patients in the group A will start with DC treatment on Day 15 of chemotherapy Cycle 3 provided.During the Induction chemotherapy period, DC will be administered on Day 15 of each subsequent 3-week chemotherapy cycle of chemotherapy. During the Maintenance chemotherapy period, DC will be administered on Day 15 of every other 3-week chemotherapy cycle.
Follow-up periods: Patients who complete or discontinue all study treatments after Cycle 3 before disease progression will undergo disease evaluation by CT scan every 3 months until progression of the disease.Patients who discontinue all study treatments before or at Cycle 2 for any reason or those who complete or discontinue all study treatments after Cycle 3 after disease progression will be followed up for survival. The survival data will be collected every 3 months by directly contacting the patient (or a relative/caretaker) by phone until death from any reason or termination of the study. The clinical study will be terminated when at least 45 PFS (progression-free survival) events have been reached, which is assumed to happen approximately 24 months after start of treatment of the first patient included in the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Small Cell Lung Cancer
Keywords
Lung Cancer, Chemotherapy, Immunotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
70 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
chemotherapy followed dendritic cells
Arm Type
Experimental
Arm Description
pemetrexed and carboplatin chemotherapy followed dendritic cells infusion from Cycle 3
Arm Title
chemotherapy
Arm Type
Active Comparator
Arm Description
pemetrexed and carboplatin chemotherapy only
Intervention Type
Biological
Intervention Name(s)
chemotherapy followed dendritic cells
Intervention Description
Pemetrexed and carboplatin would be administered on day 1 of each 3-week cycle.Patients will start with dendritic cells treatment on Day 15 of pemetrexed and carboplatin chemotherapy from Cycle 3 provided that both leukapheresis and the production of dendritic cells are successful.
Intervention Type
Drug
Intervention Name(s)
pemetrexed and carboplatin
Intervention Description
Chemotherapy with 4-6 cycles of pemetrexed and carboplatin as first-line induction chemotherapy followed by pemetrexed as maintenance therapy.
Primary Outcome Measure Information:
Title
Progression-free survival
Description
randomization to the date of an event defined as the first progression or death due to any cause (institution of a new systemic anticancer treatment will also be considered as a progression event),whichever occurs first up to 24 months
Time Frame
the time from the date of randomization to the date of an event defined as the first progression or death due to any cause, whichever occurs first, up to 24 months
Secondary Outcome Measure Information:
Title
Safety parameters in terms of AE, laboratory abnormalities, and vital signs
Description
adverse events [AEs], serious adverse events [SAEs], adverse events of special interest [AESIs], laboratory abnormalities, and vital signs
Time Frame
through study completion, an average of 24 months
Title
Overall Survival
Time Frame
From study treatment to death due to any cause, up to 24 months
Title
Objective Response Rate
Time Frame
Objective Response Rate measured by RECIST criteria in ITT population, up to 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed stage IV, non-squamous, wild-type EGFR,ALK-negative NSCLC
Signed ICF and ability to comply with this protocol
18 years of age or older
ECOG performance status of 0-1
Patients must have measurable disease as defined by RECIST v. 1.1
Systematic treatment naive with respect to the currently diagnosed NSCLC
Patients must have recovered from toxicity of previous therapy. Recovery is defined as less than or equal to grade 2 toxicity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (except alopecia).
Sufficient hematologic and organ function for leukapheresis and chemotherapy:
WBC equal to or higher than 4×10^9 /L
Neutrophil equal to or higher than 1.5×10^9 /L
PLT equal to or higher than 100×10^9 /L
Hemoglobin equal to or higher than9 g/dL (90 g/L)
Total bilirubin less than or equal to 1.5 times upper limit of normal (benign hereditary hyperbilirubinemias, eg, Gilbert's syndrome are permitted)
Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) should be less than or equal to 3 times upper limit of normal. ALP, AST, and ALT less than or equal to 5 times upper limit of normal is acceptable if liver has tumor involvement.
Creatinine clearance equal to or higher than 45 mL/min (calculated with the standard Cockcroft and Gault formula)
Women of childbearing potential and sexually active males must agree to use an accepted and effective method of contraception (hormonal or barrier methods, abstinence) prior to study entry and for the duration of the treatment plus 3 months
Exclusion Criteria:
Known active/untreated CNS metastases
Any known primary immunodeficiency
Any preexisting medical condition requiring long term chronic steroid or immunosuppressive therapy
HIV positivity, hepatitis B and/or C infection, syphilis
Past or current history of malignant neoplasm other than lung carcinoma, except for adequately treated non-melanoma skin cancer, in situ carcinoma of the cervix, or other cancer curatively treated and with no evidence of disease for at least five years
Patient's significant co-morbidities:
Cardiovascular diseases - unstable angina pectoris, uncontrolled hypertension, myocardial infarction or ventricular arrhythmia or stroke within a 6-month period before randomization, congestive heart failure or cardiac arrhythmia not controlled by treatment
Active severe infections or other severe medical condition
Participation in a clinical study using experimental therapy and immunotherapy,monoclonal antibodies within the last 4 weeks prior to study entry
Pregnant or breastfeeding woman
History of severe hypersensitivity to pemetrexed and carboplatin and their ingredients, and to DCVAC ingredients
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Baohui Han, MD
Phone
86-21-62821990
Ext
3301
Email
xkyyhan@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Hua Zhong, MD
Phone
86-21-62821990
Ext
3902
Email
eddiedong8@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Baohui Han, MD
Organizational Affiliation
Shanghai Chest Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai Chest Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200030
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Baohui Han, MD
Phone
86-21-62821990
Ext
61201
Email
xkyyhan@gmail.com
First Name & Middle Initial & Last Name & Degree
Baohui Han, MD
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Cellular Immunotherapy Synergize Chemotherapy in Patients With Stage IV NSCLC
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