Clinical Trial Assessing the Efficacy of Abscopal Effect Induced by SBRT and Immunotherapy in Advanced NSCLC

NCT04238169 | Completed Phase 2

• 1 other identifier: XQonc-014
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, multicenter, open-label study to observe the effect of SBRT and immunotherapy combined with Bevacizumab or not in stage IV non-squamous non-small cell lung cancer (NSCLC) with previously failed after chemotherapy.

Conditions

Non-Small-Cell Lung Cancer Stage IV

Outcome Measures

Primary Outcomes (2)

• Objective response rate

  Assess the efficacy (overall response rate \[ORR\]) of SBRT and Toripalimab combined with Bevacizumab or not in stage IV non-squamous NSCLC with previously failed after chemotherapy. (according to RECIST version 1.1 and EORTC 1999)

  Up to 6 months

• Objective response of non-target lesion

  Assess the efficacy (Objective response of non-target lesion) of SBRT and Toripalimab combined with Bevacizumab or not in stage IV non-squamous NSCLC with previously failed after chemotherapy. (according to RECIST version 1.1 and EORTC 1999)

  Up to 6 months

Secondary Outcomes (4)

• Progression-free survival (PFS)

  From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy (up to approximately 2 years)

• Duration of response

  From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy (up to approximately 2 years)

• Overall survival

  From date of first dose of study drug until withdrawal of consent or death (up to approximately 2 years)

• The incidence of adverse events (AEs) as a measure of safety

  For each participant, from the first participant first dose until 30 days after the last dose (up to approximately 2 years)

Study Arms (2)

SBRT+Toripalimab

EXPERIMENTAL

Immunotherapy：Toripalimab: 240 mg once every three weeks，Until progress of disease or investigators determine that clinical benefit is no longer available or there are intolerable toxicity. SBRT：30-50Gy/5F（2-4 locations).

Drug: Toripalimab; Radiation: SBRT

SBRT+Bevacizumab+Toripalimab

EXPERIMENTAL

Immunotherapy：Toripalimab: 240 mg once every three weeks，Until progress of disease or investigators determine that clinical benefit is no longer available or there are intolerable toxicity. SBRT：30-50 Grays(Gy) in 5 fractions（2-4 locations）. Bevacizumab：7.5mg/kg once every three weeks.

Drug: Bevacizumab; Drug: Toripalimab; Radiation: SBRT

Interventions

Bevacizumab DRUG

7.5mg/kg once every three weeks

SBRT+Bevacizumab+Toripalimab

Toripalimab DRUG

240 mg once every three weeks

SBRT+Bevacizumab+Toripalimab; SBRT+Toripalimab

SBRT RADIATION

30-50Gy/5F（2-4 lesions）

SBRT+Bevacizumab+Toripalimab; SBRT+Toripalimab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have signed written informed consent and able to comply with study procedures.
• Histologically and/or cytologically confirmed advanced metastatic (stage IV) non-squamous non-small cell lung cancer.
• Previous received first-line platinum-based chemotherapy or immunotherapy (except toripalimab) and followed by progression of disease evaluated by RECIST 1.1.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) Performance Status score 0-1.
• Life expectancy ≥ 12 weeks.
• Have at least 3 measurable lesions based on RECIST 1.1, at least 2 of them can be treated by SBRT.
• Adequate hematologic function as defined by the following laboratory values:
• Absolute neutrophil count ≥1.5x109/L
• Platelets ≥80 x 109/L
• Hemoglobin ≥9 g/dL
• Adequate Hepatic function: Total bilirubin ≤1.5×ULN Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN OR ≤5×ULN for patients with liver metastases.
• Adequate renal function: Creatinine ≤1.5×ULN or calculated creatinine clearance (CrCl) ≥50 mL/min and dipstick proteinuria \<2+. A 24-hour urine protein test is needed if a dipstick proteinuria result of ≥2+ is detected, the proteinuria level ≤ 1g/24h.
• International normalized ratio≤1.5 × ULN, prothrombin time (PT) or partial thromboplastin time (PTT or a PTT) ≤1.5 × ULN(within 7 days of assessment).
• Female who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile must be willing to use an adequate method of contraception.

You may not qualify if:

• Evidence of tumour invading major blood vessels on imaging. The investigator or the local radiologist must exclude evidence of tumour that is fully contiguous with, surrounding, or extending into the lumen of a major blood vessel (e.g., pulmonary artery or superior vena cava).
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device are excluded within 7 days prior to initiation of study treatment. Placement of a vascular access device should be at least 2 days prior to initiation of study treatment.
• Current or recent (within 10 days of first dose of bevacizumab) use of aspirin (325 mg/day) or other nonsteroidal anti-inflammatory agents known to inhibit platelet function.
• Current or recent (within 10 days of first dose of bevacizumab) use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic purposes. Prophylactic use of anticoagulants is allowed.
• History or evidence of inherited bleeding diathesis or coagulopathy that increases the risk of bleeding.
• Uncontrolled hypertension (blood pressures: systolic\>150 mmHg and/or diastolic \>100 mmHg).
• Prior history of hypertensive crisis or hypertensive encephalopathy.
• Clinically significant (i.e., active) cardiovascular disease, including but not limited to cerebral vascular accident (CVA) or (transient ischemic attack) TIA (≤6 months before randomization), myocardial infarction (≤6 months before randomization), unstable angina, congestive heart failure New York Heart Association Class≥II, or serious cardiac arrhythmia requiring medication during the study and that might interfere with regularity of the study treatment or not controlled by medication.
• Significant vascular disease (including but not limited to aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to randomization.
• The lesion has received prior radiotherapy and is not suitable for SBRT.
• Has stable brain metastases is allowed, but the brain metastases will not receive SBRT or whole brain radiotherapy (WBRT)
• Malignancies other than NSCLC within 2 years except for basal or squamous cell skin cancer, carcinoma in situ of the cervix and cured early stage prostate cancer.
• Corticosteroid therapy at a dose equivalent to 10 mg prednisone per day or any other systemic immunosuppressive therapy within 14 days prior to randomization. Topical or inhaled steroids are permitted. Taking immunosuppressive drugs accidentally during the trial will be allowed, but it is strongly recommended to reduce the dose as soon as possible.
• A positive HIV test result, presence of active HIV, hepatitis B or hepatitis C（evaluate at local laboratories）
• Non-healing wound, active peptic ulcer, or bone fracture.

Sponsors & Collaborators

• Xinqiao Hospital of Chongqing: lead

Study Sites (1)

Xinqiao Hospital of Chongqing

Chongqing, Chongqing Municipality, 400000, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Bevacizumab; toripalimab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: director physician

Study Record Dates

• First Submitted: January 14, 2020
• First Posted: January 23, 2020
• Study Start: September 1, 2020
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2023
• Last Updated: February 28, 2024

Record last verified: 2024-02

Locations

CN (1)