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

August 10, 2021 updated by: The First Affiliated Hospital with Nanjing Medical University

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Lingxiang Liu, Physician
  • Phone Number: (+86) 13851892074
  • Email: llxlau@163.com

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210029
        • Recruiting
        • The First Affiliated Hospital of Nanjing Medical University
        • Contact:
          • Lingxiang Liu, Dr.
          • Phone Number: +862568306577
          • Email: llxlau@163.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NSCLC patients with negative driver genes
Patients with negative driver genes advanced or metastatic NSCLC will receive sintilimab combined with anlotinib hydrochloride and platinum-containing dual-agent chemotherapy regimens as first-line treatment.
Drug: Sintilimab + Anlotinib + Pemetrexed + Cisplatin or Carboplatin
Patients with non-squamous NSCLC will receive sintilimab, anlotinib hydrochloride, pemetrexed, and cisplatin or carboplatin.
Other Names:
  • combination therapy
Drug: Sintilimab + Anlotinib + Albumin Paclitaxel + Carboplatin
Patients with squamous NSCLC will receive sintilimab, anlotinib hydrochloride, albumin paclitaxel, and carboplatin.
Other Names:
  • combination therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Object response rate (ORR)
Time Frame: Time Frame: Up to 24 moths.
Containing the incidence of complete response (CR) and partial response (PR).
Time Frame: Up to 24 moths.

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The First Affiliated Hospital with Nanjing Medical University

Investigators

  • Principal Investigator: Lingxiang Liu, Physician, The First Affiliated Hospital with Nanjing Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2021

Primary Completion (Anticipated)

May 1, 2023

Study Completion (Anticipated)

May 1, 2023

Study Registration Dates

First Submitted

April 13, 2021

First Submitted That Met QC Criteria

April 13, 2021

First Posted (Actual)

April 15, 2021

Study Record Updates

Last Update Posted (Actual)

August 12, 2021

Last Update Submitted That Met QC Criteria

August 10, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021-SR-088

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

All collected IPD and all IPD that underlie results in a publication.

IPD Sharing Time Frame

Starting 6 months after publication.

IPD Sharing Access Criteria

IPD will be shared with other related clinical trials or systematic reviews after reviewing requests by the chief investigator and examiners.

IPD Sharing Supporting Information Type

  • Study Protocol

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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