SBRT Combined With PD-1 Inhibitor and Thoracic Hyperthermia for Advanced NSCLC

NCT05520853 | Unknown Phase 2

• 1 other identifier: SBRT-PT
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this trial is to investigate the primary efficacy of SBRT combined with PD-1 inhibitor and thoracic hyperthermia in patients with EGFR, ALK, and ROS1 negative stage IV NSCLC patients who progressed after first-line treatment. At least one lesion (primary or metastatic) was selected for SBRT treatment, and the radiotherapy dose of each lesion was 32Gy/4Fx. SBRT was combined with thoracic hyperthermia from the first fraction, and hyperthermia was performed 6 times, twice a week. PD-1 inhibitor was used on the second day after the completion of SBRT. The PD-1 inhibitor was administered at a dose of 200mg every time, every 3 weeks for 2 years (35 times total), or until the investigators deem that the patient need to discontinue the drug because of treatment-related toxicity or disease progression. During the period, the overall response rate and toxicities were regularly evaluated.

Conditions

Stereotactic Body Radiation Therapy; PD-1 Inhibitor; Hyperthermia; NSCLC

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  The proportion of patients evaluated as complete response or partial response

  2 years

Secondary Outcomes (4)

• Incidence of treatment-related toxic effects

  2 years

• Objective response rate of non-irradiated lesions

  2 years

• Overall response

  2 years

• Progression free survival

  2 years

Study Arms (1)

SBRT combined with PD-1 inhibitors and thoracic hyperthermia

EXPERIMENTAL

At least one lesion (primary or metastatic) was selected for SBRT treatment, and the radiotherapy dose of each lesion was 32Gy/4Fx. SBRT was combined with thoracic hyperthermia from the first fraction, and hyperthermia was performed 6 times, twice a week. PD-1 inhibitor was used on the second day after the completion of SBRT. The PD-1 inhibitor was administered at a dose of 200mg every time, every 3 weeks for 2 years (35 times total), or until the investigators deem that the patient need to discontinue the drug because of treatment-related toxicity or disease progression.

Radiation: SBRT combined with PD-1 inhibitors and thoracic hyperthermia

Interventions

SBRT combined with PD-1 inhibitors and thoracic hyperthermia RADIATION

At least one lesion (primary or metastatic) was selected for SBRT treatment, and the radiotherapy dose of each lesion was 32Gy/4Fx. SBRT was combined with thoracic hyperthermia from the first fraction, and hyperthermia was performed 6 times, twice a week. PD-1 inhibitor was used on the second day after the completion of SBRT. The PD-1 inhibitor was administered at a dose of 200mg every time, every 3 weeks for 2 years (35 times total), or until the investigators deem that the patient need to discontinue the drug because of treatment-related toxicity or disease progression.

SBRT combined with PD-1 inhibitors and thoracic hyperthermia

Eligibility Criteria

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

You may qualify if:

• Age≥18.
• ECOG PS 0-1.
• Histopathologically confirmed stage IV non-small-cell lung cancer.
• EGFR/ALK/ROS-1 negetive.
• Disease progression after first-line therapy including platinum chemotherapy, but not include PD-1/L1 inhibitors.
• Subjects with brain metastases were eligible, but only if they had no neurologic symptoms or disease stable without systemic glucocorticoid.
• At least one lesion with a diameter of 1-5cm which could be treated with SBRT at a dose of 32Gy/4Fx, and at least one lesion which could be measured other than SBRT (RECIST1.1); Lymph nodes can be used as independent measurable lesions or receive SBRT. Brain lesions should not be used as separate SBRT lesions or as measurable lesions.
• The subjects did not had radiotherapy before.
• The subjects did not currently need palliative radiotherapy at any part according to the researchers.
• It was necessary for the subjects who underwent surgery to fully recover from the toxicity and complications caused by surgical intervention prior to treatment.
• Subjects should provide appropriate biopsy specimens before and during treatment according to the clinical trial protocol.
• Male or female subjects agree to contraception during the trial (surgical ligation or oral contraceptive/IUD + condom).
• Life expectancy ≥ 3 months.
• The organ function level meet the following standards one week before enrollment:
• ①Bone marrow: hemoglobin ≥80g/L, white blood cell count ≥4.0\*10\^9/L or neutrophil count ≥1.5\*10\^9/L, platelet count ≥100\*10\^9/L.

You may not qualify if:

• Prior treatment with anti-PD-1 /L1 drugs or other investigational immunotherapy agent.
• Subjects had prior radiotherapy.
• Subjects had severe autoimmune diseases: active inflammatory bowel disease (including Crohn's disease and ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis (such as Wegener's granuloma), etc.
• Symptomatic interstitial lung disease or active infectious/noninfectious pneumonia.
• Subjects had risk factors for bowel perforation: active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal cancer, or other risk factors for bowel perforation.
• History of other malignant tumors.
• Subjects who have current infection, heart failure, heart attack, unstable angina, or unstable arrhythmia in the last 6 months.
• Subjects with physical examination or clinical trial findings, or other uncontrolled conditions that the investigator believes may interfere with the outcome or increase the risk of treatment complications.
• Subjects without platinum-based combination chemotherapy included as first-line treatment.
• The pathology reports showed a mixture of small cell lung cancer components.
• Lactating or pregnant women.
• Congenital or acquired immunodeficiency diseases including human immunodeficiency virus (HIV), or a history of organ transplantation, allogeneic stem cell transplantation.
• Known hepatitis B virus (HBV), hepatitis C virus (HCV), active pulmonary tuberculosis infections.
• Subjects had cancer vaccines other vaccines within 4 weeks before treatment initiation. (Seasonal influenza vaccines are usually inactivated and are permitted, whereas intranasal preparations are usually live attenuated vaccines and therefore are not permitted)
• Subjects who currently use other immune agents, chemotherapy agents, other investigational drugs or long-term cortisol therapy.

Sponsors & Collaborators

• First People's Hospital of Hangzhou: lead
• Hangzhou Cancer Hospital: collaborator

Study Sites (1)

Affiliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310002, China

RECRUITING

MeSH Terms

Conditions

Hyperthermia; Carcinoma, Non-Small-Cell Lung

Interventions

Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Heat Stress Disorders; Wounds and Injuries; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Bing Xia, MD

  Hangzhou Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bing Xia, MD

CONTACT

86-0571-56006382; bxia_hzch@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: August 27, 2022
• First Posted: August 30, 2022
• Study Start: January 20, 2020
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: August 30, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)