Sintilimab, Anlotinib Hydrochloride and Platinum-Containing Dual-Agent Chemotherapy in NSCLC

Metastatic NSCLC Clinical Trial

Official title:

Sintilimab Combined With Anlotinib Hydrochloride and Standard Platinum-Containing Dual-Agent Chemotherapy in Non-Small Cell Lung Cancer (NSCLC) as First-Line Treatment: A Single-Arm, Prospective and Exploratory Clinical Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04846452
• Other study ID #: 2021-SR-088
• Status: Recruiting
• Phase: Phase 2
• Start date: June 1, 2021
• Est. completion date: May 1, 2023

Study information

• Verified date: August 2021
• Source: The First Affiliated Hospital with Nanjing Medical University
• Contact: Lingxiang Liu, Physician
• Phone: (+86) 13851892074
• Email: llxlau[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single-arm, prospective, exploratory clinical study aiming to evaluate the efficacy and safety profile of sintilimab combined with anlotinib hydrochloride and platinum-containing dual-agent chemotherapy regimens in advanced or metastatic NSCLC as first-line treatment. Totally 40 patients with negative driver genes (20 patients of squamous cell carcinoma, 20 patients of non-squamous cell carcinoma) are to be enrolled.

Description:

Sintilimab (200 mg intravenously, once every 3 weeks; Cinda Bio-Suzhou Co., Ltd., Suzhou, Jiangsu, China) and anlotinib hydrochloride (12 mg orally, once daily before breakfast; CTTQ, Lianyungang, Jiangsu, China) are to be administered as first-line therapy in NSCLC. Besides, patients with non-squamous NSCLC will also receive pemetrexed and cisplatin or carboplatin. Meanwhile, patients with squamous NSCLC will also receive albumin paclitaxel and carboplatin. Patients assessing as CR/PR/SD will continue to receive a maintenance treatment after 4-6 cycles of treatment. Patients with non-squamous NSCLC will be treated with sintilimab + anlotinib hydrochloride + pemetrexed chemotherapy regimen while patients with squamous NSCLC will be treated with sintilimab + anlotinib hydrochloride to maintain treatment for 2 years until disease progression, intolerable toxicity, death, and patient request for discontinuation or starting new anti-tumor treatment.

Observations and assessments will be conducted before treatment, on day 7, 21 of cycle 1, on day 21 of cycle 2, every 2 cycles (42 days) during the following cycles, and after treatment. Follow-up for survival status and subsequent antineoplastic therapy data collecting will be performed by telephone interview or face-to-face every 6 weeks after treatment until disease progression, death, or end of the study (whichever occurs first).

This study will be divided into two stages: the safety lead-in period and the preliminary efficacy evaluation period. The first stage is the safety lead-in period. 3 patients with squamous NSCLC and 3 patients with non-squamous NSCLC will be enrolled to evaluate the combined therapy safety. The first 6 patients will continue to be observed from the beginning of the combined treatment until the 6th patient has been treated for 2 cycles (6 weeks). If there are less than or equal to 2 patients with intolerable side effects, they will enter the next stage. A total of 40 patients (20 patients with squamous NSCLC, 20 patients of non-squamous NSCLC) will be enrolled, and the safety and efficacy of the combined treatment will be initially evaluated. All statistics will be analyzed by statistical analysis software (SAS) 9.2 (or higher version). The single-sided 0.05 superiority hypothesis test will be used to test statistics and the comparison between groups will give a 95% confidence interval and p-value.

Efficacy is to be analyzed in the full analysis set (FAS), the response evaluable set (RES), and the per-protocol set (PPS). Safety is to be analyzed in safety set (SS) including all assigned patients who receive at least one dose of study combined therapy and have safety records of medication. Statistical descriptions of subject distribution, demographic data, and baseline characteristics will be performed. For study endpoints, the Kaplan-Meier method is to be applied for the PFS and OS curve with estimation for median PFS, median OS, and 95% CI. ORR= (CR+PR) / sample size×100%; DCR= (CR+PR+SD) / sample size×100%. The 95% CI of the ORR and DCR is to be calculated by an exact binomial method based on the F distribution. For safety analysis, only treatment-emergent adverse events (TEAE) will be included and analyzed in this experiment, which is defined as AEs that are post-dose or heavier than the baseline. Medical Dictionary for Regulatory Activities (MedDRA), system organ class (SOC), preferred terms (PT) and NCI CTCAE 5.0 will be used to standardize and classify all adverse events and summarize the incidence of AEs and association with treatments.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: May 1, 2023
• Est. primary completion date: May 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 1. Voluntary provision of informed consent.

• 2. Males or females aged 18-75.

• 3. Histological or cytologically confirmed NSCLC, metastatic or recurrent (stage IV), non-resectable or radical radio-chemotherapy locally advanced (stage IIIB-IIIC).

• 4. Not suitable for targeted therapy (patients with non-squamous NSCLC have no EGFR, ALK, or ROS1 gene mutation)

• 5. At least one lesion can be measured by imaging.

• 6. Have not received systemic treatment in the past.

• 7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.

• 8. Life expectancy = 3 months.

• 9. Female of childbearing age must have a negative pregnancy test (serum or urine) within 7 days before enrolment.

Exclusion Criteria:

• 1. Histological or cytologically confirmed small cell lung cancer (SCLC), including lung cancer mixed with SCLC and NSCLC.

• 2. Received radiation therapy within 6 weeks.

• 3. Diagnosed with other malignant diseases other than NSCLC within 5 years.

• 4. Have participated in other interventional clinical research treatments now or within 4 weeks.

• 5. Have previously received targeted therapy.

• 6. Received Chinese patent medicines with anti-lung cancer indications or immunomodulatory drugs within 2 weeks.

• 7. Have active autoimmune diseases requiring systemic treatment within 2 years.

• 8. Received systemic glucocorticoid therapy or immunosuppressive therapy within 7 days.

• 9. Clinically uncontrollable pleural effusion/abdominal effusion.

• 10. Known allogeneic organ transplantation or hematopoietic stem cell transplantation.

• 11. Known to be allergic to study drug.

• 12. Have been vaccinated with the live vaccine within 30 days.

• 13. Pregnant or breastfeeding females.

• 14. Other serious hazards to the safety of patients.

Related Conditions & MeSH terms

• Advanced Non-Small Cell Squamous Lung Cancer
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Metastatic NSCLC
• Recurrent NSCLC

Intervention

Drug:
• Sintilimab + Anlotinib + Pemetrexed + Cisplatin or Carboplatin
Patients with non-squamous NSCLC will receive sintilimab, anlotinib hydrochloride, pemetrexed, and cisplatin or carboplatin.
• Sintilimab + Anlotinib + Albumin Paclitaxel + Carboplatin
Patients with squamous NSCLC will receive sintilimab, anlotinib hydrochloride, albumin paclitaxel, and carboplatin.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Nanjing Medical University	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital with Nanjing Medical University

Country where clinical trial is conducted

China, 

References & Publications (6)

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Jiang S, Liang H, Liu Z, Zhao S, Liu J, Xie Z, Wang W, Zhang Y, Han B, He J, Liang W. The Impact of Anlotinib on Brain Metastases of Non-Small Cell Lung Cancer: Post Hoc Analysis of a Phase III Randomized Control Trial (ALTER0303). Oncologist. 2020 May;25 — View Citation

McDermott DF, Atkins MB. PD-1 as a potential target in cancer therapy. Cancer Med. 2013 Oct;2(5):662-73. doi: 10.1002/cam4.106. Epub 2013 Jul 21. Review. — View Citation

Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin JHM, Beasley MB, Chirieac LR, Dacic S, Duhig E, Flieder DB, Geisinger K, Hirsch FR, Ishikawa Y, Kerr KM, Noguchi M, Pelosi G, Powell CA, Tsao MS, Wistuba I; WHO Panel. The 2015 World Health Organizati — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Object response rate (ORR)	Containing the incidence of complete response (CR) and partial response (PR).	Time Frame: Up to 24 moths.
Secondary	Progression-free survival (PFS)	From allocation to first disease progression confirmed by imaging modalities or all cause death, whichever occurs first.	Up to 24 months.
Secondary	Disease control rate (DCR)	Containing the incidence of complete response (CR), partial response (PR) and stable disease (SD).	Up to 24 months.
Secondary	Duration of Remission (DOR)	The time interval from disease remission to disease progression or death (whichever occurs first).	Up to 24 months.
Secondary	Overall survival (OS)	From allocation to any cause death or last follow-up.	Up to 24 months.