Phase I Study of Low-Dose Radiotherapy Plus Chemotherapy and Sugemalimab and Olaparib for First-Line Treatment of SLFN-11 Positive Extensive Stage Small Cell Lung Cancer
Overview
- Phase
- Phase 1
- Intervention
- Low-dose radiotherapy
- Conditions
- Lung Cancer
- Sponsor
- Sichuan University
- Enrollment
- 45
- Locations
- 1
- Primary Endpoint
- RDE
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
The purpose of this study was to evaluate the safety and efficacy of low-dose radiotherapy (LDRT) combined with sugemalimab, olaparib, chemotherapy in the first-line treatment of SLFN-11 positive extensive stage small cell lung cancer.
Detailed Description
This study consists of dose escalation and dose expansion in China. Subjects who fulfil all the inclusion criteria and none of the exclusion criteria will be enrolled and receive treatment with Sugemalimab, Etoposide/Cisplatin Chemotherapy and Olaparib for 4 cycles with LDRT in the first cycle. Sugemalimab in combination with olaparib will be administered for maintenance therapy after 4 cycles. Sugemalimab will be administered at a dose of 1200 mg every 3 weeks (Q3W) in the first day of every cycle. The LDRT deals with primary tumour in a 15 Gy of 5 fractions over five days, starting from day 1 in the first cycle. Dose of olaparib will identify by assessed recommended dose for expansion (RDE) in dose escalation stage.A dose expansion stage will be conducted after dose escalation. The primary endpoint is safety.
Investigators
You Lu
Chief of Thoracic Cancer Ward
Sichuan University
Eligibility Criteria
Inclusion Criteria
- •Men or women aged more than or equal to (≥) 18 years old and less than or equal to (≤) 75 years old
- •Histologically or cytologically confirmed ES-SCLC
- •No prior treatment for ES-SCLC
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Five white slides (unstained paraffin sections) were available for immunohistochemical SLFN-11 detection and SLFN-11 was positive
- •Extensive clinical stage. American Joint Committee on Cancer (AJCC) 8th edition Stage IV with lesions exceeding one side of the chest and including malignant pleural and pericardial effusions or hematogenous metastases (any T, any N, M1a/b/c); or T3-4 due to multiple nodules in the lung or tumor/nodule size too large to be included in a T3-4 disease within a tolerable radiotherapy schedule
- •The subjects were considered suitable for combining etoposide with cisplatin chemotherapy and low-dose radiotherapy as first-line treatment for extensive -stage small cell lung cancer
- •Have measurable lesions as defined by RECIST1.1, with at least one lesion (never previously treated with radiation) of ≥10 mm longest diameter accurately measured by computed tomography (CT) or magnetic resonance imaging (MRI) at baseline (except for lymph nodes, which must have a short axis of ≥15 mm) and the lesion is suitable for repeat and accurate measurements
- •Patients with brain metastases must be asymptomatic or stable on steroids and anticonvulsants for at least 1 month prior to study treatment. Participants with suspected brain metastases during screening should have a CT/MRI of the brain prior to study
- •No previous treatment with immune checkpoint inhibitors and PARP inhibitors, including but not limited to other anti-PD-1, anti-PD-L1 and anti-programmed cell death ligand 2 (anti-PD-L2) antibodies, with the exception of therapeutic anti-tumor vaccines. No prior chemotherapy or radiation therapy to the chest lesion
Exclusion Criteria
- •Histopathologic or cytopathologic diagnosis of mixed small cell lung cancer or non-small cell lung cancer
- •Limited stage small cell lung cancer
- •Combination of poorly controlled malignant pleural or pericardial effusions requiring continuous drainage
- •Presence of active or symptomatic brain metastases or Leptomeningeal metastases
- •Prior systemic antitumor therapy (chemotherapy, targeted agents such as PARP inhibitors) or immune checkpoint inhibitors for SCLC
- •Presence of active, unstable systemic disease such as active infection, autoimmune disease, inflammatory disease (uncontrolled hypertension, heart failure (NYHA classification \>= Class II), unstable angina, acute coronary syndrome, severe arrhythmia, severe hepatic, renal or metabolic disease, human immunodeficiency virus (HIV) immunodeficiency virus (HIV) infected patients
- •Previous allogeneic stem cell or solid organ transplantation
- •Patients with prior interstitial lung disease, drug-induced interstitial lung disease, or active interstitial pneumonia requiring systemic glucocorticoid or immunosuppressive therapy; Patients with pulmonary interstitial fibrosis or active pulmonary tuberculosis
- •Severe infection within 4 weeks prior to the start of study treatment, including but not limited to hospitalization for infection, bacteremia, or severe pneumonia
- •Received therapeutic oral or intravenous infusion of antibiotics within 2 weeks prior to the start of study treatment
Arms & Interventions
Low-dose radiotherapy combined with sugemalimab, olaparib, etoposide and cisplatin
Participants will receive the following treatment regimens: LDRT cisplatin + etoposide + sugemalimab+olaparib. Induction treatment will be administered on a 21-day cycle for four cycles. LDRT will be conducted from Day 1 - Day 5 in the first cycle. Following the induction phase, participants will continue maintenance therapy with sugemalimab and olaparib. Participants will be treated until loss of clinical benefit, or unaccepted toxicity, or withdrawal of consent, or death (whichever occurs first).
Intervention: Low-dose radiotherapy
Low-dose radiotherapy combined with sugemalimab, olaparib, etoposide and cisplatin
Participants will receive the following treatment regimens: LDRT cisplatin + etoposide + sugemalimab+olaparib. Induction treatment will be administered on a 21-day cycle for four cycles. LDRT will be conducted from Day 1 - Day 5 in the first cycle. Following the induction phase, participants will continue maintenance therapy with sugemalimab and olaparib. Participants will be treated until loss of clinical benefit, or unaccepted toxicity, or withdrawal of consent, or death (whichever occurs first).
Intervention: Etoposide
Low-dose radiotherapy combined with sugemalimab, olaparib, etoposide and cisplatin
Participants will receive the following treatment regimens: LDRT cisplatin + etoposide + sugemalimab+olaparib. Induction treatment will be administered on a 21-day cycle for four cycles. LDRT will be conducted from Day 1 - Day 5 in the first cycle. Following the induction phase, participants will continue maintenance therapy with sugemalimab and olaparib. Participants will be treated until loss of clinical benefit, or unaccepted toxicity, or withdrawal of consent, or death (whichever occurs first).
Intervention: Cisplatin
Low-dose radiotherapy combined with sugemalimab, olaparib, etoposide and cisplatin
Participants will receive the following treatment regimens: LDRT cisplatin + etoposide + sugemalimab+olaparib. Induction treatment will be administered on a 21-day cycle for four cycles. LDRT will be conducted from Day 1 - Day 5 in the first cycle. Following the induction phase, participants will continue maintenance therapy with sugemalimab and olaparib. Participants will be treated until loss of clinical benefit, or unaccepted toxicity, or withdrawal of consent, or death (whichever occurs first).
Intervention: Sugemalimab
Low-dose radiotherapy combined with sugemalimab, olaparib, etoposide and cisplatin
Participants will receive the following treatment regimens: LDRT cisplatin + etoposide + sugemalimab+olaparib. Induction treatment will be administered on a 21-day cycle for four cycles. LDRT will be conducted from Day 1 - Day 5 in the first cycle. Following the induction phase, participants will continue maintenance therapy with sugemalimab and olaparib. Participants will be treated until loss of clinical benefit, or unaccepted toxicity, or withdrawal of consent, or death (whichever occurs first).
Intervention: Olaparib
Outcomes
Primary Outcomes
RDE
Time Frame: 3 weeks after initiation of treatment.
To determine the RDE of olaparib in subjects with Extensive Stage-SCLC when combined with low-Dose Radiotherapy, chemotherapy and sugemalimab.
Secondary Outcomes
- Progression-free survival (PFS)(Baseline up to approximately 24 months)
- PFS Rate at 6 Months and 1 Year(Baseline up to 1 year)
- Overall Survival (OS)(Baseline up to approximately 24 months)
- OS Rate at 1 Year, 1.5 Years and 2 Years(Baseline to 2 years or death, whichever occurs first.)
- Objective response rate (ORR)(Baseline to 2 years)