search
Back to results

Sequential Hypofractionated Radiotherapy Followed by Anti-PD-L1 Atezolizumab for SCLC (Atezolizumab)

Primary Purpose

Small Cell Lung Cancer Recurrent

Status
Recruiting
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Atezolizumab
Sponsored by
National Cancer Center, Korea
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Small Cell Lung Cancer Recurrent

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male or female patient aged 18 years or older
  2. Histologically confirmed SCLC and available tumor tissues for PD-L1 staining
  3. Progression during or after platinum-based chemotherapy.
  4. At least one target tumor lesion that has not been irradiated within the past three months and that can accurately be measured in at least one dimension with longest diameter
  5. Life expectancy of at least three months
  6. Performance status of 0, 1, 2 on the ECOG criteria
  7. Adequate hematologic and end-organ function, Patients may be transfused or receive erythropoietic treatment to meet this criterion.
  8. Patient has given written informed consent which must be consistent with the International Conference on Harmonization - Good Clinical Practice (ICH-GCP) and local legislation

Exclusion Criteria:

  1. Previous therapy with anti-PD-1 or -PD-L1 inhibitors
  2. Persistence of clinically relevant therapy related toxicities from previous chemotherapy and/or radiotherapy
  3. Chemotherapy, treatment with tyrosine kinase inhibitors, or radiotherapy (except for brain and extremities) within the past 3 weeks prior to treatment with the trial drug i.e., the minimum time elapsed since the last anticancer therapy and the first radiotherapy must be 3 weeks
  4. Treatment with other investigational drugs or treatment in another clinical trial within the past three weeks before start of therapy or concomitantly with this trial
  5. Concomitant yellow fever vaccination
  6. Active or untreated CNS metastases as determined by CT or MRI evaluation during screening and prior radiographic assessments
  7. Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for 2 weeks prior to randomization
  8. Leptomeningeal disease
  9. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
  10. Uncontrolled tumor-related pain
  11. Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
  12. Significant cardiovascular diseases (i.e., hypertension not controlled by medical therapy, unstable angina, history of myocardial infarction within the past 12 months, congestive heart failure > NYHA II, serious cardiac arrhythmia, pericardial effusion)
  13. Proteinuria CTCAE grade 2 or greater
  14. Significant weight loss (> 10 %) within the past 6 weeks prior to treatment in the present trial
  15. Current peripheral neuropathy ≥ CTCAE(version4.0) Grade 2 except due to trauma
  16. Major injuries and/or surgery with incomplete wound healing within the past ten days prior to enrollment
  17. Serious infections requiring systemic antibiotic (e.g. antiviral, antimicrobial, antifungal) therapy
  18. Active hepatitis C and/or B infection
  19. Known human immunodeficiency virus (HIV) seropositivity
  20. Serious illness or concomitant non-oncological disease such as neurologic-,psychiatric-, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study
  21. Patients who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner for participating females, condoms for participating males) during the trial and for at least 5 months after end of active therapy
  22. Pregnancy or breast feeding
  23. Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule
  24. Patients unable to comply with the protocol
  25. Active alcohol or drug abuse
  26. Other malignancy within the past three years other than basal cell skin cancer or carcinoma in situ of the cervix

Sites / Locations

  • National Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Interventions

Arm Description

Atezolizumab

Outcomes

Primary Outcome Measures

ORR
Objective Response rate using RECIST v1.1

Secondary Outcome Measures

PFS
Progression Free Survival

Full Information

First Posted
August 23, 2017
Last Updated
April 4, 2022
Sponsor
National Cancer Center, Korea
Collaborators
Roche Korea co.,Ltd.
search

1. Study Identification

Unique Protocol Identification Number
NCT03262454
Brief Title
Sequential Hypofractionated Radiotherapy Followed by Anti-PD-L1 Atezolizumab for SCLC
Acronym
Atezolizumab
Official Title
Sequential Hypofractionated Radiotherapy Followed by Anti-PD-L1 Atezolizumab for Recurrent or Refractory Small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 22, 2018 (Actual)
Primary Completion Date
February 23, 2023 (Anticipated)
Study Completion Date
July 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Cancer Center, Korea
Collaborators
Roche Korea co.,Ltd.

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
The investigators hypothesized that local radiation therapy can enhance the effect of anti-PD-L1 monoclonal antibody through priming T-cell effector function against cancer cells. Described as above, The investigators concluded that modest dose of radiation to local site prior to immunotherapy is the best to enhance T-cell-mediated immunity. Accordingly, The investigators will investigate the combining effect of hypofractionated-sublethal dose of radiation therapy followed by anti-PD-L1 monoclonal antibody, atezolizumab, for SCLC patients who are recurrent or refractory for initial platinum-based chemotherapy
Detailed Description
Small cell lung cancer (SCLC), accounting for 10% of all lung cancers (Torre et al., 2015), shows poor outcomes with 7-10 months of median survival in advanced cases (Jett et al., 2013). Despite novel treatment strategies including targeted therapy and immunotherapy for non-small cell lung cancer (NSCLC) have been introduced, the treatment options for SCLC still remain limited. Many clinical trials, which tested the efficacy of molecular targeted agents for SCLC, failed to show clinical benefit compared with conventional platinum-based chemotherapy (Koinis et al., 2016). Nevertheless, recent studies demonstrated that immunotherapy using anti-CTLA-4 or anti-PD1 monoclonal antibody can be novel therapeutic strategies for SCLC (Ott et al., 2015; Reck et al., 2013; SJ et al., 2015). In recent years, many studies have shown that radiation therapy can be a useful treatment as a combining treatment with immunotherapy. The abscopal effect refers to the ability of radiation delivered radiation delivered to a local site to treat the other diseases outside radiation field (Tang et al., 2014). A recent study described that abscopal effect was observed in a malignant melanoma patient treated with CTLA4 antagonist and radiotherapy (Postow et al., 2012). Moreover, an animal study presented that blockade of PD-L1 and ionizing radiation showed synergism (Deng et al., 2014). Based on these emerging evidences, the investigators hypothesized that local radiation therapy can enhance the effect of anti-PD-L1 monoclonal antibody through increasing T-cell effector function against tumors. Atezolizumab, which is a humanized anti-PD-L1 monoclonal antibody, act as an inhibitor the interaction between PD-L1 and PD-1, and eventually restore suppressed T-cell immunity leading elimination of cancer cells. In this study, the investigators will investigate the combining effect of hypofractionated-sublethal dose of radiation therapy followed by anti-PD-L1 monoclonal antibody, atezolizumab, for SCLC patients who are recurrent or refractory for initial platinum-based chemotherapy. Based on these emerging evidences, the investigators hypothesized that local radiation therapy can enhance the effect of anti-PD-L1 monoclonal antibody through priming T-cell effector function against cancer cells. Described as above, the investigators concluded that modest dose of radiation to local site prior to immunotherapy is the best to enhance T-cell-mediated immunity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Small Cell Lung Cancer Recurrent

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Interventions
Arm Type
Experimental
Arm Description
Atezolizumab
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Other Intervention Name(s)
Tecentriq
Intervention Description
Patients undergo hypofractionated radiation therapy with 24 Gy over 4 fractions in days 1-4 of 1st cycle of atezolimumab and receive Atezolizumab 1200 mg fixed dose via intravenous on day 1 of each 3-week cycle until disease progression or unacceptable toxicity occurs.
Primary Outcome Measure Information:
Title
ORR
Description
Objective Response rate using RECIST v1.1
Time Frame
through study completion, and average of 1 years
Secondary Outcome Measure Information:
Title
PFS
Description
Progression Free Survival
Time Frame
From date of enroll until the date of first documented progression or date of death from any cause, whichever came first, assessed up to at least 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female patient aged 18 years or older Histologically confirmed SCLC and available tumor tissues for PD-L1 staining Progression during or after platinum-based chemotherapy. At least one target tumor lesion that has not been irradiated within the past three months and that can accurately be measured in at least one dimension with longest diameter Life expectancy of at least three months Performance status of 0, 1, 2 on the ECOG criteria Adequate hematologic and end-organ function, Patients may be transfused or receive erythropoietic treatment to meet this criterion. Patient has given written informed consent which must be consistent with the International Conference on Harmonization - Good Clinical Practice (ICH-GCP) and local legislation Exclusion Criteria: Previous therapy with anti-PD-1 or -PD-L1 inhibitors Persistence of clinically relevant therapy related toxicities from previous chemotherapy and/or radiotherapy Chemotherapy, treatment with tyrosine kinase inhibitors, or radiotherapy (except for brain and extremities) within the past 3 weeks prior to treatment with the trial drug i.e., the minimum time elapsed since the last anticancer therapy and the first radiotherapy must be 3 weeks Treatment with other investigational drugs or treatment in another clinical trial within the past three weeks before start of therapy or concomitantly with this trial Concomitant yellow fever vaccination Active or untreated CNS metastases as determined by CT or MRI evaluation during screening and prior radiographic assessments Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for 2 weeks prior to randomization Leptomeningeal disease Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures Uncontrolled tumor-related pain Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab Significant cardiovascular diseases (i.e., hypertension not controlled by medical therapy, unstable angina, history of myocardial infarction within the past 12 months, congestive heart failure > NYHA II, serious cardiac arrhythmia, pericardial effusion) Proteinuria CTCAE grade 2 or greater Significant weight loss (> 10 %) within the past 6 weeks prior to treatment in the present trial Current peripheral neuropathy ≥ CTCAE(version4.0) Grade 2 except due to trauma Major injuries and/or surgery with incomplete wound healing within the past ten days prior to enrollment Serious infections requiring systemic antibiotic (e.g. antiviral, antimicrobial, antifungal) therapy Active hepatitis C and/or B infection Known human immunodeficiency virus (HIV) seropositivity Serious illness or concomitant non-oncological disease such as neurologic-,psychiatric-, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study Patients who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner for participating females, condoms for participating males) during the trial and for at least 5 months after end of active therapy Pregnancy or breast feeding Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule Patients unable to comply with the protocol Active alcohol or drug abuse Other malignancy within the past three years other than basal cell skin cancer or carcinoma in situ of the cervix
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ji-Youn Han, Ph.D.
Phone
+82-31-920-1154
Email
jymama@ncc.re.kr
First Name & Middle Initial & Last Name or Official Title & Degree
Sung Jin Yoon
Phone
+82-31-920-0399
Email
sjyoon@ncc.re.kr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ji-Youn Han, Ph.D.
Organizational Affiliation
National Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Cancer Center
City
Goyang-si
State/Province
Gyeonggi-do
ZIP/Postal Code
10408
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ji-Youn Han, Ph.D.

12. IPD Sharing Statement

Learn more about this trial

Sequential Hypofractionated Radiotherapy Followed by Anti-PD-L1 Atezolizumab for SCLC

We'll reach out to this number within 24 hrs