Sintilimab Combined With Metformin in First-Line Chemotherapy Refractory Advanced NSCLC Patients

NCT03874000 | Unknown Phase 2 DMC

• 1 other identifier: SMART
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

Evaluate the Efficacy and Safety of Sintilimab Combined with Metformin Hydrochloride in Patients with Advanced Non-small Cell Lung Cancer Refractory to First-Line Platinum-Containing Chemotherapy

Conditions

Non Small Cell Lung Cancer

Keywords

Sintilimab; Metformin Hydrochloride; second line; cancer; NSCLC

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined as participants who had complete response (CR) or partial response(PR) divided by the total number of patients.

  each 42 days up to intolerance the toxicity or PD (up to 24 months)

Secondary Outcomes (4)

• Overall Survival (OS)

  From enrollment until death (up to 24 months)

• Progress free survival (PFS）

  each 42 days up to PD or death (up to 24 months)

• Disease Control Rate (DCR）

  each 42 days up to intolerance the toxicity or PD (up to 24 months)

• Duration of Response (DOR)

  From the first response date to PD or death (up to 24 months)

Study Arms (1)

Sintilimab plus Metformin Hydrochloride

EXPERIMENTAL

Patients receive metformin hydrochloride 500mg orally (PO) twice daily (BID). Patients also receive Sintilimab 200mg intravenously (IV) in 60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression, unacceptable toxicity, or withdrawal of consent.

Biological: Sintilimab; Drug: Metformin Hydrochloride

Interventions

Sintilimab BIOLOGICAL

Given IV

Also known as: IBI308

Sintilimab plus Metformin Hydrochloride

Metformin Hydrochloride DRUG

Given PO

Also known as: Glucophage

Sintilimab plus Metformin Hydrochloride

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated informed consent forms
• Male or female,18-75 years of ages
• Eastern Cooperative Oncology Group (ECOG) PS：0-2
• Life expectancy of more than 12 weeks
• Histologically or cytologically confirmed, non-small cell lung cancer (NSCLC) (the participant who has undergone pathological re-examination asked to take the site that had not received radiotherapy)
• Locally advanced, metastatic or recurrent \[unresectable or not meet the standard of radical radiotherapy and chemotherapy IIIB, IIIC or IV NSCLC, according to the 8th Edition of the Union Internationale Contre le Cancer (UICC)/American Joint Committee on Cancer (AJCC) Staging system\] NSCLC
• Both cases are received by first-line platinum chemotherapy failed
• ). First-line platinum chemotherapy during or after treatment (include maintenance treatment) are defined by initial progressive disease (PD) (RECIST v1.1), during first-line platinum chemotherapy received one drug was discontinued, reduced or replaced with a similar drug 2). For recurrent disease≤6 months, adjuvant chemotherapy, neoadjuvant chemotherapy or neoadjuvant chemotherapy plus adjuvant chemotherapy may be accepted, participants must have histologically confirmed, not epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) translocation 8. Histologically confirmed participants without EGFR mutation or ALK/c-ros oncogene 1 receptor kinase (ROS1) rearrangement 9. At baseline, subjects will be required to provide fresh tissue biopsy specimens, and biopsy specimens should be confirmed by a pathologist 10. Participants must have a measurable disease (RECIST v1.1) 11. At baseline, glycated hemoglobin (HbA1C)≤6.4% 12. Important organs and bone marrow functions meet the following requirements (All tests should be completed two weeks before medication, expect the participants treated with any cell and growth factor within two weeks)
• Blood routine: Absolute neutrophil (ANC)≥1.5×109/L, platelets (PLT)≥10×109/L, Hemoglobin (HGB)≥90g/L, (No transfusion or erythropoietin dependence≤14days)
• Liver functions: Total bilirubin ≤1.5 times the institutional upper limit of normal (ULN), Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SPGT\])≤2.5 X institutional ULN (or≤5 times ULN in case of liver metastasis)
• Renal functions: Creatinine(Cr)≤1.5×ULN,or creatinine clearance (CrCl)≥60milliliter (mL)/min (use Cockcroft-Gault formula) Female: CrCl=(140-age) ×weight(kg) ×0.85/72×Cr(mg/dL) Male: CrCl=(140-age) ×weight(kg) ×1.00/72×Cr(mg/dL) 13. Coagulation function: international normalized ratio(INR) or prothrombin time (PT)≤1.5 ULN; If the subject is receiving anticoagulant treatment, INR will be sufficient as long as the anticoagulant is within the prescribed range of use 14. No brain metastasis was confirmed by plain scanning and enhanced MRI /CT examination within 2 weeks before medication; Asymptomatic brain metastasis, or symptomatic brain metastasis participants who have received stereotactic radiosurgery (SRS) or whole-brain radiation therapy (WBRT) in the past, may also be included in the test if the lesion is not enlarged or the central nervous system symptoms are not evaluated by cranial MRI within 4 weeks before enrollment 15. For women of child-bearing age, a negative urine or serum pregnancy test should be conducted 3 days prior to the first study drug administration 16. Subject and subject's sexual partner will be required to use a medically approved contraceptive (such as an intrauterine device, contraceptive or condom, etc.) during and within 6 months after the study treatment period

You may not qualify if:

• Participants should not have received metformin within 6 months prior to registration
• In the past, participants have received anti PD-1, anti PD-L1 or anti PD-L2 drugs or drugs targeting another stimulation or synergistic inhibition of T cell receptors (such as Cytotoxic T-Lymphocyte Antigen 4 \[CTLA-4\] and CD137)
• Received the following treatment:
• Within 2 weeks before the first administration, 1). Received systemic therapy with Chinese adult drugs or immunomodulatory drugs (including thymosine and interferon, except for topical use to control pleural effusion) with anticancer indications 2). 4 weeks prior to the first administration, received any investigational drug therapy or use of research instruments 3). Receive an overdose of immunosuppressive agents (systemic glucocorticoid over 10 mg/ day prednisone or its equivalent) within 4 weeks prior to the first dose 4). Live vaccine was given within 4 weeks before the first dose Note: inactivated virus vaccine for seasonal influenza is allowed within 30 days prior to the first dose, but live attenuated influenza vaccine for intranasal administration is not allowed 5). Major surgery (such as an open cavity, thoracotomy, or laparotomy), or unhealed surgical wounds, ulcers, or fractures, has been performed within 4 weeks prior to the first administration 6). The adverse reactions of any previous anti-tumor treatment did not return to CTCAE ≤level 1(excluding hair loss and laboratory tests without clinical significance).
• Participants who suffer from type 1 or type 2 diabetes, or high blood sugar that require medication
• Active autoimmune diseases requiring systemic therapy (e.g. the use of disease-relieving drugs/corticosteroids or immunosuppressants) occurred within 2 years prior to the first administration. Alternative therapies (such as thyroxine or physiological corticosteroids for adrenal or pituitary insufficiency) are not considered systemic
• Allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation are known
• Allergic reaction to the active ingredients or any adjuncts of Sintilimab or metformin
• History of lactic acid or other metabolic acidosis
• Symptomatic central nervous metastasis and/or cancerous meningitis
• Interstitial pulmonary disease or previous lung disease requires oral or intravenous hormone control
• Clinically uncontrollable third interstitial effusion, such as pleural and ascites, which cannot be controlled by drainage or other methods before enrollment
• Other malignancies were diagnosed within 5 years prior to the first administration, with the exception of radical cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, and/or radical carcinoma in situ
• Other acute or chronic disease, mental illness, or laboratory abnormalities that may result in increased risk of study participation or drug administration, or interfere with the interpretation of the study results, and disqualify participants from participating in the study according to the judgment of the investigator
• Pregnant or lactating women

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead
• Innovent Biologics (Suzhou) Co. Ltd.: collaborator

Study Sites (1)

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, 300060, China

RECRUITING

Related Publications (2)

• Kubo T, Ninomiya T, Hotta K, Kozuki T, Toyooka S, Okada H, Fujiwara T, Udono H, Kiura K. Study Protocol: Phase-Ib Trial of Nivolumab Combined With Metformin for Refractory/Recurrent Solid Tumors. Clin Lung Cancer. 2018 Nov;19(6):e861-e864. doi: 10.1016/j.cllc.2018.07.010. Epub 2018 Aug 9.

  PMID: 30172698 RESULT

• Afzal MZ, Mercado RR, Shirai K. Efficacy of metformin in combination with immune checkpoint inhibitors (anti-PD-1/anti-CTLA-4) in metastatic malignant melanoma. J Immunother Cancer. 2018 Jul 2;6(1):64. doi: 10.1186/s40425-018-0375-1.

  PMID: 29966520 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms

Interventions

sintilimab; Metformin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Dingzhi Huang, M.D.

  Tianjin Medical University Cancer Institute and Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dingzhi Huang, M.D.

CONTACT

+86 18622221232; dingzhih72@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: SPONSOR

Study Record Dates

• First Submitted: March 12, 2019
• First Posted: March 14, 2019
• Study Start: March 8, 2019
• Primary Completion: February 28, 2022
• Study Completion: June 5, 2022
• Last Updated: March 19, 2019

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be available within 6 months of study completion
• Access Criteria: Data access requests will be reviewed by an external independent Review Panel. Requestors will be required to sign a Data Access Agreement.

Locations

CN (1)