Match: Study of Low-Dose Radiotherapy (LDRT) Concurrent Cisplatin/Carboplatin Plus Etoposide With Atezolizumab for Patients With Extensive-Stage Small Cell Lung Cancer

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04622228

Collaborator

(none)

Enrollment

Locations

Arm

39.5

Anticipated Duration (Months)

6.9

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase II, single arm, multicenter study designed to evaluate the safety and efficacy of low-dose radiotherapy (LDRT) concurrent cisplatin/carboplatin plus etoposide with atezolizumab in participants who have extensive-stage small cell lung cancer (ES-SCLC) and are chemotherapy-navïe for their extensive-stage disease.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Small Cell Lung	Drug: Atezolizumab Drug: Cisplatin Drug: Carboplatin Drug: Etoposide Radiation: Thoracic radiation therapy (TRT)	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

55 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II, Single-Arm Study of Low-Dose Radiotherapy (LDRT) Concurrent Cisplatin/Carboplatin Plus Etoposide With Atezolizumab for Patients With Extensive-Stage Small Cell Lung Cancer

Actual Study Start Date :

Dec 16, 2020

Anticipated Primary Completion Date :

Sep 29, 2022

Anticipated Study Completion Date :

Apr 2, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LDRT concurrent cisplatin/carboplatin + etoposide + atezolizumab Participants will receive the following treatment regimens: LDRT concurrent cisplatin/carboplatin + etoposide + atezolizumab. Induction treatment will be administered on a 21-day cycle for four cycles. Concurrent radiation therapy will be conducted from Day 1 - Day 5 in the first cycle. Following the induction phase, participants will continue maintenance therapy with atezolizumab. Participants will be treated until loss of clinical benefit, or unaccepted toxicity, or withdrawal of consent, or death (whichever occurs first).	Drug: Atezolizumab Atezolizumab will be administered by intravenous infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, and clinical status. Other Names: Tecentriq Drug: Cisplatin Cisplatin will be administered as intravenous infusion at a dose of 75 mg per meter squared (75 mg/m^2) after completion of atezolizumab on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4). Drug: Carboplatin Carboplatin will be administered as intravenous infusion at a dose of area under the concentration-time curve (AUC) of 5 mg/mL/min on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4). Drug: Etoposide Etoposide will be administered intravenously at a dose of 100 mg/m^2 on Days 1, 2 and 3 of each 21-day cycle during the induction phase (Cycles 1-4). Radiation: Thoracic radiation therapy (TRT) Participants will receive concurrent thoracic radiation therapy (TRT) treatment, in once daily fractions, 3 Gy per fraction, to a target dose of 15 Gy in 5 fractions from Day 1-Day 5 in the first cycle.

Arm

Intervention/Treatment

Experimental: LDRT concurrent cisplatin/carboplatin + etoposide + atezolizumab

Participants will receive the following treatment regimens: LDRT concurrent cisplatin/carboplatin + etoposide + atezolizumab. Induction treatment will be administered on a 21-day cycle for four cycles. Concurrent radiation therapy will be conducted from Day 1 - Day 5 in the first cycle. Following the induction phase, participants will continue maintenance therapy with atezolizumab. Participants will be treated until loss of clinical benefit, or unaccepted toxicity, or withdrawal of consent, or death (whichever occurs first).

Drug: Atezolizumab

Atezolizumab will be administered by intravenous infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, and clinical status.

Other Names:

Tecentriq

Drug: Cisplatin

Cisplatin will be administered as intravenous infusion at a dose of 75 mg per meter squared (75 mg/m^2) after completion of atezolizumab on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4).

Drug: Carboplatin

Carboplatin will be administered as intravenous infusion at a dose of area under the concentration-time curve (AUC) of 5 mg/mL/min on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4).

Drug: Etoposide

Etoposide will be administered intravenously at a dose of 100 mg/m^2 on Days 1, 2 and 3 of each 21-day cycle during the induction phase (Cycles 1-4).

Radiation: Thoracic radiation therapy (TRT)

Participants will receive concurrent thoracic radiation therapy (TRT) treatment, in once daily fractions, 3 Gy per fraction, to a target dose of 15 Gy in 5 fractions from Day 1-Day 5 in the first cycle.

Outcome Measures

Primary Outcome Measures

Objective Response Rate [Baseline up to approximately 36 months]
Objective response rate (ORR), defined as the proportion of participants with a complete response (CR) or partial response (PR) on two consecutive occasions >= 4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).

Secondary Outcome Measures

Duration of Response [Baseline to disease progression or death from any cause (whichever occurs first)(up to approximately 36 months)]
Duration of response (DOR), defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1.
Disease Control Rate (DCR) [Baseline up to approximately 36 months]
Disease control rate (DCR), defined as the proportion of participants who have a best overall response of CR or PR or stable disease (SD), as determined by the investigator according to RECIST v1.1.
Progression Free Survival (PFS) [Baseline to the first occurrence of disease progression or death from any cause (whichever occurs first) (up to approximately 36 months)]
Progression Free Survival (PFS), defined as the time from initiation of study treatment to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1.
PFS Rate at 6 Months and 1 Year [Baseline up to 1 year]
PFS rate at 6 months and 1 year, defined as the proportion of patients who have not experienced disease progression or death from any cause at 6 months and 1 year separately, as determined by the investigator according to RECIST v1.1.
Overall Survival (OS) [Baseline until death (up to approximately 36 months)]
OS, defined as the time from initiation of study treatment to death from any cause.
OS Rate at 1 Year and 2 Years [Baseline to 2 years or death, whichever occurs first.]
OS rate at 1 year and 2 years, defined as the proportion of patients who have not experienced death from any cause at 1 year and 2 years.
Percentage of Participants With Adverse Event [Baseline up to approximately 36 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or cytologically confirmed ES-SCLC
No prior treatment for ES-SCLC
Measurable disease, as defined by RECIST v1.1. Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation.
ECOG performance status of 0 or 1
Life expectancy >= 3 months
Adequate hematologic and end-organ function
For participants receiving therapeutic anticoagulation: stable anticoagulant regimen
Negative human immunodeficiency virus (HIV) test at screening
Negative hepatitis B surface antigen (HBsAg) test at screening
Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb at screening accompanied by either of the following: Negative total hepatitis B core antibody (HBcAb), or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test. The HBV DNA test will be performed only for participants who have a negative HBsAg test, a negative HBsAb test, and a positive total HBcAb test.
Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test will be performed only for participants who have a positive HCV antibody test.
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm

Exclusion Criteria:

Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
Participants with pulmonary artery invasion
History of leptomeningeal disease
Uncontrolled tumor-related pain
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
Uncontrolled or symptomatic hypercalcemia
Active or history of autoimmune disease or immune deficiency
History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
Active tuberculosis
Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
History of malignancy other than small cell lung cancer (SCLC) within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Cancer Hospital , Chinese Academy of Medical	Beijing City	China	100021
2	Hunan Cancer Hospital	Changsha City	China	410013
3	West China Hospital - Sichuan University	Chengdu City	China	610047
4	Second Affiliated Hospital of Third Military Medical University	Chongqing	China	400030
5	Fudan University Shanghai Cancer Center; Medical Oncology	Shanghai City	China	201315
6	Shanghai Pulmonary Hospital	Shanghai	China	200433
7	Tianjin Cancer Hospital	Tianjin	China	300060
8	Central South Hospital, Wuhan University	Wuhan	China	430000

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT04622228

Other Study ID Numbers:

ML42391

First Posted:

Nov 9, 2020

Last Update Posted:

Jul 6, 2022

Last Verified:

Jul 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Additional relevant MeSH terms:

Small Cell Lung Carcinoma

Carcinoma, Small Cell

Carboplatin

Etoposide

Atezolizumab

Study Results

No Results Posted as of Jul 6, 2022