Assessing Safety and Efficacy of Sintilimab and Metformin Combination Therapy in SCLC

NCT03994744 | Unknown Phase 2

• 1 other identifier: HNCH-SCLC-2019260
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

In this Single arm study, histologically or cytologically confirmed ED-stage small cell lung cancer (SCLC) patients resistant to or relapsed after standard chemotherapy will be enrolled to investigate the Efficacy and Safety of a Combination of Sintilimab and Metformin. Primary outcome: Objective response rate (ORR), Safety of the combination therapy Secondary outcome: Overall survival (OS), Progression-free survival (PFS), Duration of response(DOR),

Conditions

Small-cell Lung Cancer; Small Cell Lung Carcinoma; Small Cell Lung Cancer Recurrent; Small Cell Lung Cancer Extensive Stage

Keywords

immunotherapy; metformin; PD-L1; PD-1 checkpoint inhibitor

Outcome Measures

Primary Outcomes (2)

• Objective response rate of Sintilimab and Metformin(ORR)

  Assessing the response of treatment of each patient using RECIST 1.1 criteria, the investigators calculate the percentage of patients meet partial response (30% decrease in diameter) and complete response in the arm.

  1 year

• Safety of the combination therapy of Sintilimab and Metformin: CTCAE4.03 grading

  Incidence and severity of (serious) adverse events in each individual according to the CTCAE4.03 grading.

  2 year

Secondary Outcomes (3)

• Median overall survival (OS) time of Sintilimab and Metformin

  2 years

• Median progression free survival(PFS) of Sintilimab and Metformin

  1 year

• Median duration of response (DoR) of Sintilimab and Metformin

  1 year

Study Arms (1)

Sintilimab and Metformin

EXPERIMENTAL

Participants will be given intravenous administration of Sintilimab (1200mg/3w) Metformin treatment will be given (day20) 1 week before the second administration of Sintilimab a a dose of 2000 mg daily (1000mg BID). The duration of treatment will be up to one year, or till the disease progression, death, or unacceptable toxicity show up.

Drug: PD-1 inhibitor; Drug: Metformin

Interventions

PD-1 inhibitor DRUG

Intravenous administration of Sintilimab (1200mg/3weeks)

Also known as: Sintilimab, IBI380

Sintilimab and Metformin

Metformin DRUG

Metformin treatment will be given (day20) 1 week before the second administration of Sintilimab at a dose of 2000 mg daily (1000mg BID). To reduce GI toxicity, participants start Metformin at 1000 mg daily (500mg am, 500 mg pm) for 1 week.

Sintilimab and Metformin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patient, age≥18 and≤65;
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2;
• The life expectancy of greater than 12 weeks;
• Participants must have histologically or cytologically confirmed metastatic or extended disease of SCLC (ED-SCLC).
• According to RECIST1.1, participants must have been confirmed Disease progression (within 6 months, confirmed by imaging test)after platinum-based doublet chemotherapy OR after (PFS\>6 months, ) platinum-based doublet chemotherapy and refused to continue chemotherapy, OR after second-line or more lines of systemic chemotherapy limited disease SCLC (LD-SCLC) patients with disease progression after Synchronous chemoradiotherapy, must receive firstline systematic platinum-based doublet chemotherapy and refused to receive chemotherapy again.
• Evaluable or measurable lesion is required, defined as at least one lesion (not brain metastasis) that can be accurately measured based on RECIST 1.1;
• Participant need to provided tumor tissue (from an archival tumor sample obtained within 1 year or from a new biopsy sample) for PD-L1 immunohistochemical (IHC) assay, and PD-L1expression in more than 1% cells is required;
• Participant is able to the ability to swallow oral medications
• Participants have to meet the following criteria to ensure function of vital organs:
• Absolute neutrophil count (ANC) ≥1.5×109/L or White blood cell count \>3.5×109/L;Platelets \>80×109/L; Hemoglobin (HGB)≥90 g/L;Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN); AST(SGOT)/ALT(SGPT) ≤2.5 ×ULN; ALB≥2.8g/dL;Serum creatinine ≤ 1.5 x institutional ULN OR creatinine clearance ≥40 mL/min using the Cockcroft-Gault equation
• Participants must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) through the treatment, and for at least 180 days after the last dose of study treatment; Participants must have the ability to understand and be willing to sign a written informed consent document.

You may not qualify if:

• Participants who were diagnosed as mixed pathological type of small cell lung cancer
• Participants who had long-term use of metformin (\>2 weeks) 6 months prior to study entry, or diagnosed with type-2 diabetes,
• Participants received treatment with anti-PD1, -PDL1, -CTLA4, -CD137 inhibitors before, or any therapy specifically targeting T-cell co-stimulation or checkpoint pathways.
• Participants received cellular immunotherapy before
• Participants with Uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection; Known history of Human Immunodeficiency Virus (HIV) infection Acute or chronic active hepatitis B (HBV DNA \>1\*10\^3 copies/ml or \>200 IU/mL) or, acute or chronic active hepatitis C (with a positive Hepatitis C antibody test result) Active tuberculosis Congestive heart failure (Class III-IV, according to New York Heart Association classification), or and clinically significant Cardiac arrhythmia if poorly controlled; Uncontrolled arterial hypertension (systolic blood pressure ≥160mmHg or diastolic blood pressure ≥100mmHg) Any arterial thrombosis, embolism, ischemia, myocardial infarction, unstable angina, or cerebrovascular accident within 6 months prior to enrollment,
• Participants with symptomatic Central nervous metastasis or meningeal carcinomatosis are excluded; Participants with asymptomatic brain metastases or with brain metastases that have been treated and stable in a subsequent scan are allowed to include if there is measurable lesion outside the Central nervous system and no history of intracranial hemorrhage, and not midbrain, pons, cerebellum, medulla or spinal cord metastasis, and do not need glucocorticoid therapy.
• Participants receiving glucocorticoid (\>30 mg prednisone equivalent a day) or any Immunosuppressive drug within 14 days prior to study recruitment; Participants receiving inhaled or Topical corticosteroids, adrenal corticosteroid replacement therapy (\>10 mg prednisone equivalent a day) are allowed if they have no active autoimmune disease
• Participants with a known additional malignancy (Except for Non-melanoma skin cancer and the following in situ carcinoma: in situ bladder carcinoma, in situ gastric carcinoma, in situ colonic carcinoma, in situ endometrial carcinoma, in situ cervical carcinoma /dysplasia, in situ melanoma carcinoma and in situ breast Carcinoma) unless they Maintained Complete Remission for at least 5 years and do not need corresponding treatment during the study
• Participants who have not recovered (i.e., ≤ Grade 1 according to NCI CTCAE V4or at baseline) from adverse effects due to a previously administered agent.
• Participants who have uncontrollable effusion, such as pleural and ascites that cannot be controlled by drainage or other treatment
• Patients who have active autoimmune diseases; excluding patients whose active autoimmune disease is caused by Vitiligo or asthma that is completely relieved in childhood and Patients with hypothyroidism requiring only hormone replacement therapy
• Patients with known Allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation
• Patients who are pregnant or breastfeeding,
• Patients who are allergic to monoclonal antibody drugs

Sponsors & Collaborators

• Hunan Cancer Hospital: lead
• Xiangya Hospital of Central South University: collaborator
• Innovent Biologics (Suzhou) Co. Ltd.: collaborator

Study Sites (1)

Hunan Cancer hospital

Changsha, Hunan, 410000, China

RECRUITING

Related Publications (1)

• Aden D, Sureka N, Zaheer S, Chaurasia JK, Zaheer S. Metabolic Reprogramming in Cancer: Implications for Immunosuppressive Microenvironment. Immunology. 2025 Jan;174(1):30-72. doi: 10.1111/imm.13871. Epub 2024 Oct 27.

  PMID: 39462179 DERIVED

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

Immune Checkpoint Inhibitors; sintilimab; Metformin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Lin Wu

  Hunan Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lin Wu, Prof.

CONTACT

+86 13170419973; wulin-calf@vip.163.com

Xingxiang Pu, Prof.

CONTACT

+86 15874180022; pxx_1354@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician, director of department

Model Details: Patients fulfilling Eligibility Criteria will be included in our study. Participants will be given intravenous administration of Sintilimab (1200mg/3w). Metformin treatment will be given (day20) 1 week before the second administration of Sintilimab at a dose of 2000 mg daily (1000mg BID). Treatments will be administrated for one year or until disease progression, death, or unacceptable toxicity. Regular follow-up and safety assessment: Patients were assessed for drug safety and treatment efficacy every 2 cycles (6 weeks) in the first 3 months after enrollment, and then evaluated every 4 cycles (12 weeks). Assessment of tumor response, adverse events. Follow-up until disease progression and patient death.

Study Record Dates

• First Submitted: June 19, 2019
• First Posted: June 21, 2019
• Study Start: August 20, 2019
• Primary Completion: August 1, 2021
• Study Completion: July 1, 2022
• Last Updated: August 28, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: please contact the principal investigator of this study or correspondence author of published wotk.

Locations

CN (1)