Sintilimab Combined With Anlotinib in Third Line or Beyond Among Advanced SCLC Patients
Study Details
Study Description
Brief Summary
Small cell lung cancer (SCLC) accounts for 10-15% of lung cancer. More than 70% of SCLC patients are diagnosed with advanced stage initially. SCLC is highly chemo-sensitive, the first-line treatment is platinum-containing double-drug chemotherapy. Although the objective response rate (ORR) of first-line chemotherapy is as high as 60-80%, the duration of response is very short, and there is little effective follow-up treatment. The outcome of SCLC patients is poor with an overall survival (OS) of about 10 months.
In August 2018, the FDA approved Nivolumab as a third-line treatment for advanced SCLC patients, which is the only immunotherapeutic drug approved for SCLC till now. Sintilimab is another PD-1 inhibitor produced by China and has been approved by cFDA for lymphoma. Anlotinib is a novel multi-target tyrosine kinase inhibitor (TKI) with effect of anti-tumor angiogenesis and tumor growth inhibition. The results of ALTER1202 show that compared with placebo, Anlotinib single-agent as three-line treatment in advanced SCLC was effective, the median progression free survival (PFS) were 4.1 versus 0.7 months, respectively (P < 0.0001).
Immunotherapy combined with anti-angiogenic therapy has been proven effective and tolerable in non-small cell lung caner (NSCLC), while its efficacy and safety in SCLC has not been reported. Therefore, the investigators conduct this study to evaluate the efficacy and safety of Sintilimab combined with Anlotinib versus Anlotinib alone in third line or beyond among advanced SCLC patients.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Sintilimab combine with Anlotinib Sintilimab 200mg intravenously on day 1 and Anlotinib 12mg per os on day 1-14 of each 3-week cycle |
Drug: Sintilimab
Sintilimab 200mg intravenously on day 1 of each 3-week cycle
Drug: Anlotinib
Anlotinib 12mg per os on day 1-14 of each 3-week cycle
|
| Active Comparator: Anlotinib Anlotinib 12mg per os on day 1-14 of each 3-week cycle |
Drug: Anlotinib
Anlotinib 12mg per os on day 1-14 of each 3-week cycle
|
Outcome Measures
Primary Outcome Measures
- PFS [6 months]
progression free survival
Secondary Outcome Measures
- OS [1years]
overall survival
- ORR [6 months]
objective response rate
- DCR [6 months]
disease control rate
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Pathological or cytologically proven small cell lung cancer, at advanced stage according to VALG, and is not suitable for local treatment.
-
Progressed after at least two line standard treatment regimen (at least one treatment regimen consisting of platinum).
-
≥1 measurable lesions based on RECIST v1.1 criteria.
-
Previous radiotherapy was allowed, but the radiotherapy area must be <25% of the bone marrow area (Cristy and Eckerman 1987) and no total pelvic or chest irradiation was used; the previous radiotherapy must have been completed for at least 4 weeks before the start of study drugs treatment, and the acute toxicity must have been restored; radiotherapy of local lesions cannot be included in measurable lesions unless significant progression is noted after radiotherapy.
-
Prior surgery was allowed, provided that the treatment was completed at least 4 weeks before the start of study drugs treatment, and the acute toxicity must have been restored.
-
≥18 years old.
-
Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
-
Life expectancy > 12 weeks.
-
Adequate bone marrow, hepatic and renal function.
-
Systolic blood pressure ≤160mmHg and diastolic pressure ≤90mmHg within 7 days prior to randomization.
-
Patients must sign study specific informed consent before registration.
Exclusion Criteria:
-
Patients with brain metastasis, but those with asymptomatic brain metastasis can be enrolled.
-
Patients with meningeal metastasis.
-
Prior treatment with PD-1 inhibitor, PD-L1 inhibitor, CTLA4 inhibitor, or anti-angiogenic treatment.
-
Accept any other anti-tumor treatment simultaneously.
-
Diagnosed with active autoimmune diseases (congenital or acquired), such as interstitial pneumonia (patients with completely relieved vitiligo or childhood can be enrolled; patients with hypothyroidism and only need hormone replacement therapy can be rerolled; Patients with type 1 diabetes can also be enrolled).
-
Patients with hemorrhage tendency including acute hemorrhage of digestive tract, continuous hemorrhage disease or coagulation function disorder disease.
-
Patients are using warfarin, heparin or aspirin (>325 mg/day) or NSAIDS to inhibit platelet function within 10 days prior to enrollment, or receiving dipyridamole, ticlopidine, clopidogrel or Cilostazol treatment.
-
Patients with accompanying diseases that seriously endanger the safety of the patient or affect the patient's completion of the study.
-
Pregnant or lactating female.
-
Prior other malignant diseases, except for cervical carcinoma in situ, papillary thyroid carcinoma, or non-melanoma skin cancer.
-
Allergy to any component of the study drugs.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Henan Cancer Hospital | Zhengzhou | Henan | China | 450000 |
Sponsors and Collaborators
- Henan Cancer Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 20190328