Small Cell Lung Cancer
Conditions
Keywords
pembrolizumab, paclitaxel
Brief summary
Patients with refractory SCLC. Patients will be treated with paclitaxel and pembrolizumab.
Detailed description
Open, uncontrolled, multi-center, phase II study.
Interventions
DRUGpembrolizumab, paclitaxel
pembrolizumab, paclitaxel
Sponsors
Seoul National University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Be willing and able to provide written informed consent/assent for the trial. 2. Be 20 years of age on day of signing informed consent. 3. Have measurable lesions based on RECIST 1.1. 4. Have provided tissue from an archival tissue sample obtained after the last previous treatment or newly obtained core or excisional biopsy of a tumor lesion. 5. Have a performance status of 0 or 1 on the ECOG Performance Scale. 6. Demonstrate adequate organ function as defined below 'adequate organ fuction laboratory values', all screening labs should be performed within 10 days of treatment initiation. 'adequate organ fuction laboratory values' System Laboratory Value Hematological Absolute neutrophil count (ANC) ≥ 1,500 /mcL Platelets ≥100,000 / mcL Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L Renal Serum creatinine OR Measured or calculateda creatinine clearance (GFR can also be used in place of creatinine or CrCl)≤1.5 X upper limit of normal (ULN) OR ≥ 60 mL/min for subject with creatinine levels \>1.5 X institutional ULN Hepatic Serum total bilirubin≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR * 5 X ULN for subjects with liver metastases Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) * 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants aCreatinine clearance should be calculated per institutional standard. 7. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 8. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 5.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year. 9. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
Exclusion criteria
1. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment. 2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. 3. Has had a prior anti-cancer monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 4. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. * Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. * Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. 5. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy. 6. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. 7. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 8. Has evidence of interstitial lung disease or active, non-infectious pneumonitis. 9. Has an active infection requiring systemic therapy. 10. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 11. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 12. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. 13. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). 14. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 15. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). (inactive HBsAg carriers with prophylactic antiviral agent are allowed) 16. Has received a live vaccine within 30 days prior to the first dose of trial treatment. 17. Has a known history of active TB (Bacillus Tuberculosis) 18. Has known hypersensitivity to MK-3475 or any of its excipients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | 3 months | Tumor response will be assessed based on modified RECIST 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | from first dose to disease progression or death due to any cause, whichever came first, up to 24months | Tumor response will be assessed based on modified RECIST 1.1 |
| Overall Response (OS) | from first dose to death due to any cause, whichever came first, assessed up to 24 months | Tumor response will be assessed based on modified RECIST 1.1 |
| Safety(Toxicity) | 3 months | Safety will be assessed for all subjects and documented according to the CTCAE v4.0 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability | 3 months | find out predictive biomarker for pembrolizumab. Factors potentially associated with pembrolizumab response will b analyzed for providing the rationale for future patient selection. |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Paclitaxel Pembrolizumab * PD-L1 Induction phase : Paclitaxel 175 mg/m2, Day 1 q 3weeks, intravenous,
* Post Induction treatment phase: Paclitaxel 175 mg/m2, Day 1 q 3weeks (maximum up to total 6 cycles) + pembrolizumab 200 mg D1 q 3 weeks, intravenous,
* Maintenance phase: pembrolizumab 200 mg D1 q 3 weeks, intravenous till PD or unacceptable toxicity
pembrolizumab, paclitaxel: pembrolizumab, paclitaxel | 26 |
| Total | 26 |
Baseline characteristics
| Characteristic | Paclitaxel Pembrolizumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 17 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 68.5 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 26 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment South Korea | 26 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 26 |
| other Total, other adverse events | 26 / 26 |
| serious Total, serious adverse events | 9 / 26 |
Outcome results
Primary
Objective Response Rate
Tumor response will be assessed based on modified RECIST 1.1
Time frame: 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Paclitaxel Pembrolizumab | Objective Response Rate | 6 Participants |
Secondary
Overall Response (OS)
Tumor response will be assessed based on modified RECIST 1.1
Time frame: from first dose to death due to any cause, whichever came first, assessed up to 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paclitaxel Pembrolizumab | Overall Response (OS) | 9.1 months |
Secondary
Progression-free Survival
Tumor response will be assessed based on modified RECIST 1.1
Time frame: from first dose to disease progression or death due to any cause, whichever came first, up to 24months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paclitaxel Pembrolizumab | Progression-free Survival | 5.0 months |
Secondary
Safety(Toxicity)
Safety will be assessed for all subjects and documented according to the CTCAE v4.0
Time frame: 3 months
Other Pre-specified
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
find out predictive biomarker for pembrolizumab. Factors potentially associated with pembrolizumab response will b analyzed for providing the rationale for future patient selection.
Time frame: 3 months