Effect of Combination Therapy on SCLC After Initial Treatment Failure

Effect of Radiotherapy Concurrent With PARP Inhibitor + Temozolomide Combined With Immune Checkpoint Inhibitor on SCLC After Initial Treatment Failure

SCLC patients after initial treatment failure are treated with SBRT and low-dose radiotherapy concurrent with PARP inhibitors + temozolomide +PD-1/PD-L1 inhibitors for two cycles at least, then PARP inhibitors+temozolomide+PD-1/PD-L1 inhibitors two cycles, PD-1/PD-L1 inhibitors maintenance therapy lasted for up to 2 years.

Study Overview

• Status: Not yet recruiting
• Conditions: Small-cell Lung Cancer

Detailed Description

SCLC is easy to relapse and drug resistance soon after initial treatment , although radiotherapy and chemotherapy is sensitive at first treatment. Topotecan monotherapy is recommended in the NCCN guidelines for second-line standard treatment and the CSCO SCLC guidelines for diagnosis and treatment 2020 edition, but its effective rate is low, 24% for platinum-sensitive relapse, 2-6% for platinum-resistant, overall PFS is about 3-4 months and OS is about 6-8 months. Although immunotherapy have been successful at the first-line and third-line treatments of SCLC in the extensive stage , the second-line treatment has not achieved a breakthrough, and the effective rate of third-line immune single drug is between 10-20%.It is an important challenge and breakthrough to effectively improve the efficacy and survival of second-line treatment of SCLC. Immunocombination therapy is an important strategy to improve the efficacy. Some studies have shown that PARP inhibitors and low-dose radiotherapy can improve the efficacy of immunotherapy. PARP inhibitors are not only sensitizers of chemoradiotherapy, but also immunomodulators. High dose radiotherapy has the effect of in situ vaccine and increases tumor antigen release presentation. Low dose radiotherapy promotes the penetration of immune cells into tumor stroma and tumor bed and increases immune response. The combination of high and low dose radiotherapy and immunization can improve the immune effect and increase the incidence of distant effect. So the objective of this study is to observe the efficacy and safety of second-line treatment of SCLC with SBRT and low-dose radiotherapy combined with PARP inhibitor + temozolomide and PD-1 /PD-L1 inhibitor.

• Study Type: Observational
• Enrollment (Anticipated): 48

Contacts and Locations

• Study Contact: Name: Lijun Tan, Dr.; Phone Number: 18686777217; Email: tlj777@sina.com
• Study Contact Backup: Name: Chengling Chu, Dr.; Phone Number: 86-0451-85553590; Email: 1514432794@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

SCLC patients after initial treatment failure

Description

Inclusion Criteria:

Age ≥18 years old, ≤80 years old, expected survival ≥3 months;Pathologically confirmed SCLC with recurrence and metastasis after initial treatment;KPS score ≥70 points;Satisfied the following laboratory diagnostic indicators: hemoglobin ≥110g/L, leukocyte 4.0-10.0×109/L, neutrophils 2.0-7.5×109/L, platelet ≥100×109/L;Creatinine ≤ upper normal limit (UNL);ALT and AST≤2.5×UNL, alkaline phosphatase (ALP) ≤5×UNL, total bilirubin (TBIL) ≤ UNL;Signed informed consent.

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Exclusion Criteria:

1. Pregnant or lactating women;
2. Secondary tumor;
3. HIV carriers;
4. Serious medical diseases such as heart and lung;
5. Patients with uncontrollable mental history, unable to cooperate with treatment;
6. Autoimmune system disease, symptomatic interstitial lung disease;
7. Patients with active infection, chronic infection, acute infection, etc., and body inflammation;
8. Patients who had used hormones or antibiotics 1 month prior to treatment. -

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3 Month Objective Remission Rate	The patients have complete remission and partial remission on 3 months after radiotherapy and chemotherapy.	Up to 5 years
Progression-Free Survival	Will be described using standard Kaplan-Meier methodologies. The median PFS time, 1-year rate, 3-year PFS rate and 5-year PFS rate will be estimated and presented with 90% confidence intervals.	From chemotherapy completion until progress or death, assessed up to 5 years
Time To Progression	Time involved from research start until progress for tumor	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Will be described using standard Kaplan-Meier methodologies. The median survival time, 1-year survival rate, 3-year survival rate , 5-year survival rate and will be estimated and presented with 90% confidence intervals.	From chemotherapy completion until death, assessed up to 5 years
Number of Participants With Serious Adverse Events Related to treatment	Toxicity assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4	up to 5 years

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Harbin Medical University
• Investigators: Study Director: Daxin Zhang, Dr., First Affiliated Hospital of Harbin Medical University

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2021
• Primary Completion (Anticipated): March 1, 2024
• Study Completion (Anticipated): March 1, 2024

Study Registration Dates

• First Submitted: March 8, 2021
• First Submitted That Met QC Criteria: March 8, 2021
• First Posted (Actual): March 10, 2021

Study Record Updates

• Last Update Posted (Actual): March 10, 2021
• Last Update Submitted That Met QC Criteria: March 8, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: SBRT, low dose radiotherapy, PARP inhibitor, PD-1,PD-L1
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma
• Other Study ID Numbers: 2020IIT037

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: There is not decision to make individual participant data available to other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No