Status:

UNKNOWN

Study of Toripalimab for Limited-Stage Small Cell Lung Cancer Following Concurrent Chemoradiotherapy

Lead Sponsor:

Sun Yat-sen University

Collaborating Sponsors:

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou Panyu Central Hospital

Conditions:

Small Cell Lung Cancer Limited Stage

Eligibility:

All Genders

18-75 years

Phase:

PHASE2

Brief Summary

The phase II, randomised study is to explore the efficacy and safety of toripalimab as consolidation therapy in patients with limited-stage small cell lung cancer who have not progressed following con...

Eligibility Criteria

Inclusion

  • Provision of signed, written and dated informed consent prior to any study specific procedures;
  • Male or female aged 18-75 years;
  • Histologically- or cytologically-documented SCLC;
  • Stage I-III (AJCC/UICC 8th TNM Staging), with all lesions can be included in a tolerable radiotherapy field (limited-stage);
  • Previous thoracic radiotherapy (45 Gy twice daily or 60-66 Gy once daily) and concurrent etoposide and platinum for four cycles; Dose coverage ≥ 85% of PTV-GTV. Radiotherapy started before the completion of the third cycle of chemotherapy;
  • CR, PR or SD after concurrent chemoradiotherapy (RECIST v1.1);
  • PCI is allowed and should be completed within 90 days after the completion of chemoradiotherapy;
  • Randommization shoud be completed within 90 days after the completion of chemoradiotherapy;
  • Life expectancy ≥12 weeks;
  • World Health Organization (WHO) Performance Status of 0 or 1;
  • Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients within 7 days before the use of study drug (HCG has a minimum sensitivity of 25 IU/L or equivalent);
  • Women must be non-breastfeeding;
  • Women of reproductive age (WOCBP) must agree to comply with the contraceptive method during the study toripalimab treatment and for a period of 3 months following the last administration of the study treatment (i.e., 30 days \[ovulation cycle\] plus approximately 5 half-lives of the study drug);
  • Men who have sex with WOCBP must agree to comply with the contraceptive method during the study nivolumab treatment and for 5 months after the last administration of the study treatment (i.e. 90 days \[sperm renewal cycle\] plus approximately 5 half-lives of the study drug);
  • Spermless men do not have to comply with contraceptive requirements. WOCBP who continues to be asexual with the opposite sex does not have to comply with contraceptive requirements, but must still undergo the pregnancy tests described in this section;
  • Adequate organ and marrow function as defined below:
  • Forced expiratory volume in 1 second (FEV1) ≥ 800ml;
  • Absolute neutrophil count ≥1.5 x 10\^9/L (1500 per mm3);
  • Platelets ≥100 x 10\^9/L (100,000 per mm3);
  • Haemoglobin ≥ 9.0 g/dL (5.59 mmol/L);
  • Serum creatinine clearance (CL) ≥ 50 mL/min by the Cockcroft-Gault formula (Cockcroft and -Gault 1976);
  • Serum bilirubin ≤1.5 x upper limit of normal (ULN);
  • Aspartate Transaminase (AST) and Alanine Transaminase (ALT) ≤ 2.5 x ULN.

Exclusion

  • Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study;
  • Mixed small cell and non-small cell lung cancer histology;
  • Extensive-stage SCLC;
  • Histologically-confirmed malignant pleural or pericardial effusion;
  • Sequential chemoradiotherapy, or radiotherapy did not start before the completion of the third cycle of chemotherapy;
  • Progressive disease after concurrent chemoradiotherapy (RECIST v1.1) and before randomization;
  • Prior use of surgery, radiotherapy or chemotherapy for SCLC, with the exceptions of thoracic concurrent chemoradiotherapy and PCI;
  • Any unresolved toxicity CTCAE \>Grade 2 from the prior chemoradiation therapy will be excluded from randomization;
  • Patients with Grade ≥2 pneumonitis from prior chemoradiation therapy will be excluded from randomization;
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of toripalimab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Systemic steroid administration required to manage toxicities arising from radiation therapy delivered as part of the previous chemoradiotherapy for SCLC is allowed;
  • Prior exposure to any anti-programmed cell death protein(PD)-1 or anti-PD-L1 antibody;
  • Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access);
  • Active or prior documented autoimmune disease within the past 2 years including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's granuloma, Sjogren's syndrome, Guillain Barre syndrome or multiple sclerosis;
  • History of primary immunodeficiency;
  • History of organ transplant that requires therapeutic immunosuppression;
  • Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Bazett's Correction;
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses, hepatitis C , human immunodeficiency virus (HIV), or patients with positive HBsAg and HBV-DNA \> 500 IU/ml, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent;
  • Known history of tuberculosis;
  • Receipt of live attenuated vaccination within 30 days prior to study entry;
  • History of another primary malignancy within 5 years prior to study entry, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ, breast intraductal carcinoma in situ or localized prostate cancer;
  • Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control;
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of the toripalimab or interpretation of patient safety or study results;
  • Any condition that, in the opinion of the investigator, not suitable for study entry.

Key Trial Info

Start Date :

June 1 2020

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

May 31 2024

Estimated Enrollment :

170 Patients enrolled

Trial Details

Trial ID

NCT04418648

Start Date

June 1 2020

End Date

May 31 2024

Last Update

November 28 2022

Active Locations (1)

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Sun Yat-sen University Cancer Center

Guangzhou, China, 510060