Effect of Combination Therapy on SCLC After Initial Treatment Failure

Small-cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04790955
• Other study ID #: 2020IIT037
• Status: Not yet recruiting
• Start date: March 1, 2021
• Est. completion date: March 1, 2024

Study information

• Verified date: February 2021
• Source: First Affiliated Hospital of Harbin Medical University
• Contact: Lijun Tan, Dr.
• Phone: 18686777217
• Email: tlj777[@]sina.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 48
• Est. completion date: March 1, 2024
• Est. primary completion date: March 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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. -

Related Conditions & MeSH terms

• Small Cell Lung Carcinoma
• Small-cell Lung Cancer

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
First Affiliated Hospital of Harbin Medical University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	3 Month Objective Remission Rate	The patients have complete remission and partial remission on 3 months after radiotherapy and chemotherapy.	Up to 5 years
Primary	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
Primary	Time To Progression	Time involved from research start until progress for tumor	Up to 5 years
Secondary	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
Secondary	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