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Combined Simvastatin and Irinotecan in Treating ES-SCLC Patients Relapsed From 1st Chemotherapy

Primary Purpose

Small Cell Lung Cancer

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Irinotecan

Simvastatin

About this trial

This is an interventional treatment trial for Small Cell Lung Cancer focused on measuring ES-SCLC, Chemo-resistance, Simvastatin

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients must be volunteered to participate in the clinical trial. Patients must sign the informed Consent form (ICF) and be willing to follow and be able to complete all test procedures.

Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group [VALG] staging system).

No patients with resectable or radical radiotherapy lung cancer. Patient must have no Epidermal Growth Factor Receptor (EGFR) mutation, Anaplastic lymphoma kinase (ALK) rearrangement, or ROS proto-oncogene 1 , receptor tyrosine kinase(ROS1) rearrangement.

Patient must be at least resistant to the first-line chemotherapy. Patients must have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Patients can tolerate chemotherapy.

Exclusion Criteria:

Unclear diagnosis of SCLC. Resectable or radical radiotherapy SCLC. Contraindicated chemotherapy. Undergoing other active malignancies within 5 years or at the same time.Patients with localized curable tumors, such as basal cell carcinoma, squamous cell carcinoma, superficial bladder carcinoma, prostate carcinoma in situ, cervical carcinoma in situ, or breast carcinoma in situ, will not be excluded.

Positive test result for human immunodeficiency virus (HIV). Positive test result for active tuberculosis. Live vaccine was administered within 28 days of initial administration. Inactivated viral vaccines for seasonal influenza are allowed, except for live attenuated intranasal vaccines.

Pregnant or lactating women. A history of psychotropic substance abuse, drug abuse, or alcoholism. Other factors assessed by the sponsors.

Sites / Locations

CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences
Shanghai pulmonary hospital, Tongji University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Simvastatin + Irinotecan

Irinotecan

Arm Description

received intravenous infusions of Irinotecan 60 milligrams per square meter (mg/m^2) on Day 1,8 of every 21-day cycle (4 cycles) in combination with oral simvastatin (20mg daily) (10 months)

received intravenous infusions of Irinotecan 60 milligrams per square meter (mg/m^2) on Day 1,8 of every 21-day cycle (4 cycles)

Outcomes

Primary Outcome Measures

Progression-free survival (PFS)

To evaluate the progression-free survival (PFS) of patients.

Secondary Outcome Measures

Disease control rate (DCR)

To assess disease control rate (DCR) after treatment.

Overall response rate (ORR)

To assess best overall response rate (ORR) after treatment.

Overall survival (OS)

To estimate overall survival (OS) of patients with ES-SCLC.

Number of participants with treatment-related adverse events (AE) as assessed by CTCAE v4.0

To evaluate the toxicity profile.

Full Information

NCT ID

NCT04985201

First Posted

July 26, 2021

Last Updated

August 6, 2021

Sponsor

Shanghai Pulmonary Hospital, Shanghai, China

Collaborators

Chinese Academy of Sciences

1. Study Identification

Unique Protocol Identification Number

NCT04985201

Brief Title

Combined Simvastatin and Irinotecan in Treating ES-SCLC Patients Relapsed From 1st Chemotherapy

Official Title

Clinical Study of Irinotecan With or Without Simvastatin in Treating Extensive-Stage Small Cell Lung Cancer Patients Relapsed From First-line Chemotherapy

Study Type

Interventional

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Unknown status

Study Start Date

November 1, 2021 (Anticipated)

Primary Completion Date

December 1, 2022 (Anticipated)

Study Completion Date

August 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Shanghai Pulmonary Hospital, Shanghai, China

Collaborators

Chinese Academy of Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This Phase II study was designed to evaluate the safety and efficacy of irinotecan in combination with simvastatin compared with treatment with irinotecan alone in ES-SCLC patients relapsed from first-line chemotherapy. Participants will be divided in a 1:1 ratio to receive either irinotecan (4 cycles) + simvastatin (10 months) or irinotecan (4 cycles) until progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Treatment can be continued until persistent radiographic PD or symptomatic deterioration.

Detailed Description

PRIMARY OBJECTIVES: I.To evaluate the progression-free survival (PFS) of patients with extensive stage-small cell lung cancer (ES-SCLC) treated with irinotecan + simvastatin or with irinotecan alone. SECONDARY OBJECTIVES: I.To assess best overall response rate (ORR) after treatment. II.To assess disease control rate (DCR) after treatment. III.To estimate overall survival (OS) of patients with ES-SCLC. IV. To evaluate the toxicity profile of irinotecan + simvastatin. EXPLORATORY OBJECTIVES: I.To evaluate biomarkers correlatives. II.To explore the mechanism of irinotecan + simvastatin in the treatment of chemotherapy-resistant participants with ES-SCLC. OUTLINE: Patients are divided into two arms. ARM A: Participants received intravenous infusions of irinotecan 60 milligrams per square meter (mg/m^2) on Day 1,8 of every 21-day cycle (4 cycles) in combination with oral simvastatin (40mg daily) （10 months）until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. ARM B:Participants received intravenous infusions of irinotecan 60 milligrams per square meter (mg/m^2) on Day 1,8 of every 21-day cycle (4 cycles) until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Small Cell Lung Cancer

Keywords

ES-SCLC, Chemo-resistance, Simvastatin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Simvastatin + Irinotecan

Arm Type

Experimental

Arm Description

received intravenous infusions of Irinotecan 60 milligrams per square meter (mg/m^2) on Day 1,8 of every 21-day cycle (4 cycles) in combination with oral simvastatin (20mg daily) (10 months)

Arm Title

Irinotecan

Arm Type

Active Comparator

Arm Description

received intravenous infusions of Irinotecan 60 milligrams per square meter (mg/m^2) on Day 1,8 of every 21-day cycle (4 cycles)

Intervention Type

Drug

Intervention Name(s)

Irinotecan

Other Intervention Name(s)

Irinotecan injection

Intervention Description

Irinotecan intravenous infusion was administered at a dose of 60 mg/m^2 on Day 1,8 of each 21-day cycle.

Intervention Type

Drug

Intervention Name(s)

Simvastatin

Other Intervention Name(s)

Simvastatin 40mg

Intervention Description

Simvastatin 40 mg daily oral tablet taken.

Primary Outcome Measure Information:

Title

Progression-free survival (PFS)

Description

To evaluate the progression-free survival (PFS) of patients.

Time Frame

12 weeks

Secondary Outcome Measure Information:

Title

Disease control rate (DCR)

Description

To assess disease control rate (DCR) after treatment.

Time Frame

6 weeks

Title

Overall response rate (ORR)

Description

To assess best overall response rate (ORR) after treatment.

Time Frame

6 weeks

Title

Overall survival (OS)

Description

To estimate overall survival (OS) of patients with ES-SCLC.

Time Frame

24 weeks

Title

Number of participants with treatment-related adverse events (AE) as assessed by CTCAE v4.0

Description

To evaluate the toxicity profile.

Time Frame

24 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients must be volunteered to participate in the clinical trial. Patients must sign the informed Consent form (ICF) and be willing to follow and be able to complete all test procedures. Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group [VALG] staging system). No patients with resectable or radical radiotherapy lung cancer. Patient must have no Epidermal Growth Factor Receptor (EGFR) mutation, Anaplastic lymphoma kinase (ALK) rearrangement, or ROS proto-oncogene 1 , receptor tyrosine kinase(ROS1) rearrangement. Patient must be at least resistant to the first-line chemotherapy. Patients must have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Patients can tolerate chemotherapy. Exclusion Criteria: Unclear diagnosis of SCLC. Resectable or radical radiotherapy SCLC. Contraindicated chemotherapy. Undergoing other active malignancies within 5 years or at the same time.Patients with localized curable tumors, such as basal cell carcinoma, squamous cell carcinoma, superficial bladder carcinoma, prostate carcinoma in situ, cervical carcinoma in situ, or breast carcinoma in situ, will not be excluded. Positive test result for human immunodeficiency virus (HIV). Positive test result for active tuberculosis. Live vaccine was administered within 28 days of initial administration. Inactivated viral vaccines for seasonal influenza are allowed, except for live attenuated intranasal vaccines. Pregnant or lactating women. A history of psychotropic substance abuse, drug abuse, or alcoholism. Other factors assessed by the sponsors.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Yayi He, MD,PHD

Phone

+86 21 65115006

doctorjael@qq.com

Facility Information:

Facility Name

CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200031

Country

China

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Hongbin Ji, PHD

Phone

+86-21-54921108

hbji@sibcb.ac.cn

First Name & Middle Initial & Last Name & Degree

Hongbin Ji, PHD

Facility Name

Shanghai pulmonary hospital, Tongji University

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200433

Country

China

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yayi He, MD,PHD

Phone

+86 21 65115006

doctorjael@qq.com

First Name & Middle Initial & Last Name & Degree

Yayi He, MD,PHD

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

IPD is not available to other researchers.

Citations:

PubMed Identifier

33285097

Citation

Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Ozguroglu M, Ji JH, Garassino MC, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Thiyagarajah P, Jiang H, Paz-Ares L; CASPIAN investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):51-65. doi: 10.1016/S1470-2045(20)30539-8. Epub 2020 Dec 4.

Results Reference

result

PubMed Identifier

32346071

Citation

Gelsomino F, Tiseo M, Barbieri F, Riccardi F, Cavanna L, Frassoldati A, Delmonte A, Longo L, Dazzi C, Cinieri S, Colantonio I, Sperandi F, Lamberti G, Brocchi S, Tofani L, Boni L, Ardizzoni A. Phase 2 study of NAB-paclitaxel in SensiTivE and refractory relapsed small cell lung cancer (SCLC) (NABSTER TRIAL). Br J Cancer. 2020 Jul;123(1):26-32. doi: 10.1038/s41416-020-0845-3. Epub 2020 Apr 29. Erratum In: Br J Cancer. 2021 Jul;125(2):306.

Results Reference

result

PubMed Identifier

30641276

Citation

Chen Y, Li X, Zhang R, Xia Y, Shao Z, Mei Z. Effects of statin exposure and lung cancer survival: A meta-analysis of observational studies. Pharmacol Res. 2019 Mar;141:357-365. doi: 10.1016/j.phrs.2019.01.016. Epub 2019 Jan 11.

Results Reference

result

PubMed Identifier

16170339

Citation

Khanzada UK, Pardo OE, Meier C, Downward J, Seckl MJ, Arcaro A. Potent inhibition of small-cell lung cancer cell growth by simvastatin reveals selective functions of Ras isoforms in growth factor signalling. Oncogene. 2006 Feb 9;25(6):877-87. doi: 10.1038/sj.onc.1209117.

Results Reference

result

PubMed Identifier

12467231

Citation

Holstein SA, Hohl RJ. Synergistic interaction of lovastatin and paclitaxel in human cancer cells. Mol Cancer Ther. 2001 Dec;1(2):141-9.

Results Reference

result

Learn more about this trial

Combined Simvastatin and Irinotecan in Treating ES-SCLC Patients Relapsed From 1st Chemotherapy

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