Small-cell Lung CancerPhase 2NCT03994744
Assessing Safety and Efficacy of Sintilimab and Metformin Combination Therapy in SCLC
A Phase 2 study testing PD-1 inhibitor and Metformin in people with Small-cell Lung Cancer and Small Cell Lung Carcinoma, run by Hunan Cancer Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Small-cell Lung Cancer, Small Cell Lung Carcinoma, Small Cell Lung Cancer Recurrent
- What is being tested?
- PD-1 inhibitor and Metformin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteChina
- Study dates
- 20 Aug 2019to 1 Jul 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
Show all 11Show fewer
- 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.
Who cannot join
- 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 >110^3 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,
Show all 17Show fewer
- 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
- Patients who have contraindications to metformin including severe allergic reactions and intolerance
- Patients who are not eligible for this study, as Assessed by Investigator
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Hunan Cancer hospital
Changsha, Hunan, 410000
Xing xiang Pu, Dr., +86 0731-89762301, puxingxiang@hnca.org.cn
Lin Wu, Dr., +86 0731-89762300, wulin-calf@vip.163.com
About this study
Official title: A Phase II Open-label, Single-arm Study Assessing the Efficacy and Safety of Combination Therapy of Sintilimab and Metformin With Relapsed PD-L1 Positive Small Cell Lung Cancer
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),
Read the detailed description
Exploratory Endpoints:
The association between the efficacy of the combination treatment and changes in CTC counts after administration of the treatment.
Evaluating the correlation between programmed death ligand 1 (PD-L1) expression derived from circulating tumor cells (CTC) and tumor tissue cells, and the predictive role of CTC PD-L1 expression in ED-SCLC.
The compositional changes in the gut microbiota after administration of the treatment and its association with the efficacy of the combination treatment.
- Conditions
- Small-cell Lung Cancer, Small Cell Lung Carcinoma, Small Cell Lung Cancer Recurrent, Small Cell Lung Cancer Extensive Stage
- Being tested
- PD-1 inhibitor, Metformin
- Keywords
- immunotherapy, metformin, PD-L1, PD-1 checkpoint inhibitor
- Medical subject headings
- Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PD-1 inhibitorDrug
Also called Sintilimab, IBI380
Intravenous administration of Sintilimab (1200mg/3weeks)
MetforminDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: PD-1 inhibitor; Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 2 year
Secondary outcomes (3)
Median overall survival (OS) time of Sintilimab and Metformin
Use K-M to estimate the median OS of single arm.
Measured: 2 years
Median progression free survival(PFS) of Sintilimab and Metformin
Use K-M to estimate the median PFS of single arm.
Measured: 1 year
Median duration of response (DoR) of Sintilimab and Metformin
Use K-M to estimate the median DoR of single arm.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2019
- Study start20 Aug 2019
- Primary completion1 Aug 2021 (estimated)
- Study completion1 Jul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Small-cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hunan Cancer Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lin Wu, Hunan Cancer Hospital
- Investigators
- Lin Wu, Principal investigator, Hunan Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03994744
- Sponsor's protocol ID
- HNCH-SCLC-2019260
- Status last verified
- Aug 2019
- First submitted
- 19 Jun 2019
- Last updated
- 28 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
Publications
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.
PubMed 39462179
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Open-label, Single-arm Study Assessing the Efficacy and Safety of Combination Therapy of Sintilimab and Metformin With Relapsed PD-L1 Positive Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT03994744
- Acronym / sponsor ID
- HNCH-SCLC-2019260
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 68 participants (estimated)
- Lead sponsor
- Hunan Cancer HospitalUniversity, hospital or other
- Collaborators
- Xiangya Hospital of Central South University, Innovent Biologics (Suzhou) Co. Ltd.
- Study start
- 20 Aug 2019 (actual)
- Primary completion
- 1 Aug 2021 (estimated)
- Study completion
- 1 Jul 2022 (estimated)
- First posted
- 21 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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),
Detailed description
Exploratory Endpoints:
The association between the efficacy of the combination treatment and changes in CTC counts after administration of the treatment.
Evaluating the correlation between programmed death ligand 1 (PD-L1) expression derived from circulating tumor cells (CTC) and tumor tissue cells, and the predictive role of CTC PD-L1 expression in ED-SCLC.
The compositional changes in the gut microbiota after administration of the treatment and its association with the efficacy of the combination treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Sintilimab and Metformin | Experimental | Drug: PD-1 inhibitor, Drug: MetforminParticipants 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (17 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PD-1 inhibitorAlso: Sintilimab, IBI380Intravenous administration of Sintilimab (1200mg/3weeks) | Drug | Sintilimab and Metformin |
| MetforminMetformin 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. | Drug | Sintilimab and Metformin |
Primary outcome
Objective response rate of Sintilimab and Metformin(ORR)
Time frame: 1 year
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.
Safety of the combination therapy of Sintilimab and Metformin: CTCAE4.03 grading
Time frame: 2 year
Incidence and severity of (serious) adverse events in each individual according to the CTCAE4.03 grading.
3 secondary outcomes
Median overall survival (OS) time of Sintilimab and Metformin
Time frame: 2 years
Median progression free survival(PFS) of Sintilimab and Metformin
Time frame: 1 year
Median duration of response (DoR) of Sintilimab and Metformin
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2019.
- Derived from this study: PubMed 39462179Aden 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.
- Individual participant dataSharing planned: Yes. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
Related trials for Small-cell Lung Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
RecruitingPhase 2
A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity
Carcinoma, Neuroendocrine, Tumor, Neuroendocrine
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lin Wu principal investigator
Hunan Cancer Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PD-1 inhibitor and Metformin in people with Small-cell Lung Cancer and Small Cell Lung Carcinoma, run by Hunan Cancer Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lin Wu, Prof. (+86 13170419973, wulin-calf@vip.163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate of Sintilimab and Metformin(ORR) (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03994744, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2019.