Clinical Trial of Sintilimab Combined With Gemcitabine/Carboplatin Regimen in the Treatment of Advanced Primary Pulmonary Lymphoepithelioma-like Carcinoma

Exploratory Clinical Trial of Sintilimab Combined With Gemcitabine/Carboplatin Regimen in the Treatment of Advanced Primary Pulmonary Lymphoepithelioma-like Carcinoma（LELC）

The trial was designed to explore the safety and efficacy of sintilimab combined with gemcitabine and carboplatin in the treatment of advanced LELC.

Study Overview

• Status: Unknown
• Conditions: Lung Cancer; Primary Pulmonary Lymphoepithelioma-like Carcinoma
• Intervention / Treatment: Drug: Sintilimab combined with Gemcitabine and Carboplatin

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Recruiting
      • Zhou Chengzhi

Participation Criteria

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. age 18-75, male or female;
• 2. patients with advanced (inoperable stage iiiib -IV) primary pulmonary lymphoepithelioid carcinoma diagnosed pathologically, with at least one measurable lesion meeting RECIST v1.1 criteria;
• 3. patients have not received systemic therapy before (patients who have received platinum-containing adjuvant chemotherapy, neoadjuvant chemotherapy or radical chemoradiotherapy for advanced disease can enter if the disease progression occurs 6 months after the end of the last treatment);
• 4. ECOG PS: 0-1; expected survival ≥12 weeks;
• 5. vital organ functions meet the following requirements (excluding the use of any blood components or cytokines during screening) :The absolute count of neutrophils ≥1.5×109/L;Platelet ≥90×109/L;Hemoglobin ≥9g/dL;Serum albumin ≥3g/dL;Thyroid stimulating hormone (TSH) ≤ULN (if abnormal, T3 and T4 levels should be examined at the same time; if T3 and T4 levels are normal, they can be included in the group);Bilirubin ≤ULN;ALT and AST≤1.5 ULN;AKP 2.5 x ULN or less;Serum creatinine ≤1.5 ULN or creatinine clearance ≥60mL/min;
• 6. women of childbearing age must have been using reliable contraception or have had a pregnancy test (serum or urine) within 7 days prior to enrollment and have had negative results and be willing to use appropriate methods of contraception during the trial and 8 weeks after the last administration of the trial drug. For men, consent must be given to appropriate methods of contraception or surgical sterilization during the trial and 8 weeks after the last administration of the trial drug;
• 7. subjects voluntarily participate in this study and sign informed consent, with good compliance and follow up.

Exclusion Criteria:

• 1. those who have used other drugs to study drugs in clinical trials within 4 weeks before the first drug use;
• 2. the presence of any active autoimmune diseases or a history of autoimmune diseases (as follows, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, or decreased thyroid function; Subjects with vitiligo or with complete remission of asthma in childhood were included without any intervention in adulthood. Subjects with asthma requiring medical intervention with bronchodilators were not included.
• 3. subjects who are using immunosuppressive agents, or systemic, or absorbable local hormone therapy for immunosuppressive purposes (dose >10mg/ day prednisone or other therapeutic hormones) and continue to use within 2 weeks prior to enrollment;
• 4. severe allergic reaction to monoclonal antibody;
• 5. subjects with clinically symptomatic CNS metastases (e.g. cerebral edema, need for hormone intervention, or progression of brain metastases). Patients who have received previous treatment for brain or meningeal metastasis, such as clinical stability (MRI) has been maintained for at least 2 months, and who have stopped systemic sex hormone therapy (dose >10mg/ day prednisone or other therapeutic hormones) for more than 2 weeks can be included.
• 6. subjects have heart clinical symptoms or diseases that are not well controlled, such as: a. NYHA grade 2 or above heart failure; B. unstable angina pectoris; C. Had myocardial infarction within 1 year; D. Supraventricular or ventricular arrhythmias of clinical significance require treatment or intervention;
• 7. subjects who have previously received radiotherapy, chemotherapy, hormone therapy, surgery or molecular targeted therapy, and who have received less than 4 weeks before the study (or 5 drug half-lives, with the selected time) after the completion of the treatment (the last medication); Adverse events caused by previous treatment (except hair loss) did not recover to ≤ 1 degree CTCAE;
• 8. subjects with congenital or acquired immune deficiency (such as HIV infection) or active hepatitis (hepatitis b reference: HBsAg positive, HBV DNA≥2000 IU/ml or copy number ≥104/ml; Hepatitis c reference: positive HCV antibody;
• 9. subjects with active infection or unexplained fever >38.5 degrees during screening or before first administration;
• 10. subjects with congenital or acquired immune deficiency (such as HIV infection) or active hepatitis (hepatitis b reference: HBsAg positive, HBV DNA≥2000 IU/ml or copy number ≥104/ml; Hepatitis c reference: positive HCV antibody;
• 11. other malignancies (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix of the cervix) that the subjects had had or had at the same time;
• 12. according to the researcher's judgment, the subjects have other factors that may lead to the forced termination of this study, such as other serious diseases (including mental diseases) requiring combined treatment, severe laboratory examination abnormalities, accompanied by family or social factors, which may affect the safety of the subjects, or the collection of data and samples.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Sintilimab+Gemcitabine+Carboplatin

Drug: Sintilimab combined with Gemcitabine and Carboplatin; The patients will received Gemcitabine1000mg/m2(d1,d8)(iv)+carboplatin AUC 5 (d1)(iv),4 cycles, Sintilimab 200 mg (3mg/kg when the weight <40kg ) (d1) (iv) in one cycle every 3 weeks, until PD or death. Radiological examinations (according to the RECIST 1.1 criteria) at baseline will be repeated for tumor response evaluation following every two cycles of chemotherapy. Patients will be followed up to 30 days after the last dose of study chemotherapy, and then every 3 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate (ORR)	ORR was defined as the percentage of participants with confirmed objective tumor response, complete response (CR) or partial response (PR), as determined by investigator using RECIST v1.1 criteria	Approximately 18 months
safety(Adverse Events)	Safety will be assessed according to common terminology criteria for adverse events version 4.0 (CTC AE 4.0)	From the day the patient signs informed consent form until 30 days after last dose of sintilimab
quality of life（the patient report outcome）	Each patient answers to specific questions in questionnaire The time frame of most questions is "How would you rate your quality fo life during the last month"	From the day the patient received treatment until 30 days after last dose of sintilimab

Collaborators and Investigators

• Sponsor: Zhou Chengzhi

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2020
• Primary Completion (Anticipated): August 1, 2021
• Study Completion (Anticipated): August 1, 2022

Study Registration Dates

• First Submitted: March 12, 2020
• First Submitted That Met QC Criteria: March 16, 2020
• First Posted (Actual): March 18, 2020

Study Record Updates

• Last Update Posted (Actual): March 18, 2020
• Last Update Submitted That Met QC Criteria: March 16, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: lung cancer; Carboplatin; gemcitabine; sintilimab
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Carboplatin
• Other Study ID Numbers: CROC2001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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