Overview

Safety and Tolerability of Low Dose Radiotherapy Concurrent SBRT and PD-1 Inhibitors in Advanced NSCLC.

Status:
Not yet recruiting

Trial end date:
2024-12-31

Target enrollment:
0

Participant gender:
All

Summary

This pilot phase I trial aims to investigate the safety and tolerability of low dose radiotherapy (LDRT) and concurrent partial stereotactic body radiation therapy (SBRT) in combination with programmed cell death-1 (PD-1) inhibitors in Stage IV non-small cell lung cancer (NSCLC) patients who have failed standard therapy. At least 14 participants will be enrolled in this study. All will take part at West China Hospital, Sichuan University.

Phase:

Phase 1

Accepts Healthy Volunteers?

Details

Lead Sponsor:

Sichuan University

Treatments:

Immune Checkpoint Inhibitors

Criteria

Inclusion Criteria:

1. Be willing and able to provide written informed consent/assent for the trial.

2. Be ≥18 years of age on day of signing informed consent.

3. Patients with histologically or cytologically confirmed stage IV NSCLC.

4. Be willing to undergo repeat biopsy of tumor lesions according to the study protocol.

5. Patients who have failed the standard therapy, or who are unsuitable for standard
treatment, or refuse chemotherapy.

6. At least one measurable lesion according to RECIST 1.1. A lesion that has previously
received radiotherapy can be considered a target lesion only if this lesion is clearly
progressed after radiotherapy.

7. The target lesions (irradiated lesions) are > 5cm in in diameter

8. ECOG 0-2.

9. Life expectancy of > 3 months.

10. Patients must have normal organ and bone marrow function as defined below: Total
bilirubin Oxaloacetic Transaminase (SGOT)/ Alanine Aminotransferase (ALT) Serum Glutamic-Pyruvic
Transaminase (SGPT) <2.5 X institutional upper limit of normal ( ULN for subjects with liver metastases) *WBC >/= 3500/uL, ANC >/= 1500/uL *Platelets
>/= 90K/ul *Hemoglobin >/= 9g/dL *Creatinine 50 ml/min（Cockcroft-Gault equation）. Coagulation: International Normalized Ratio
(INR)≤ 1.5 × ULN, Partial thromboplastin time (PTT) ≤1.5 × ULN; left ventricular
ejection fraction (LVEF) >/= 50% and QTcF (Fridericia's formula) ≤ 450ms

11. Patients has recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a
previously administered agent.

12. Wash out period for chemotherapy is more than ≥ 4 weeks, for targeted small molecule
therapy ≥ 5 half-lives; palliative radiotherapy must have been completed for at least
≥ 2 weeks, chest radiotherapy must have been completed for at least ≥ 4 weeks, and
major surgery must have been completed for ≥ 4 weeks.

13. Subjects with no severe pulmonary ventilation dysfunction, no acute heart failure, and
no contraindication to radiotherapy as judged by the radiotherapist. Subjects who
agree to receive immunotherapy and radiotherapy treatment.

14. Subjects should agree to use an adequate method of contraception.

Exclusion Criteria:

1. Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis and/or spinal cord compression, etc.

2. With oncologic emergencies that require immediate treatment

3. EGFR/ALK/ROS-1 mutation or mutation status unknown.

4. Has evidence of interstitial lung disease or active and/or non-infectious pneumonitis
(drug-induced pneumonia, radiation-induced pneumonia, etc.) requiring steroid therapy.

5. History of pulmonary fibrosis, pulmonary hypertension, severe irreversible airway
obstruction disease

6. Patients with peripheral neuropathy.

7. Significant heart disease or impairment of cardiac function

8. Fluid accumulating in the third space, such as pericardial effusion, pleural effusion
and peritoneal effusion that remains uncontrolled by aspiration or other treatment

9. Known allergy to drugs or excipients, known severe allergic reaction to any of the
PD-1 monoclonal antibodies

10. Severe infection within 4 weeks prior to the start of study treatment, including but
not limited to hospitalization for infection, bacteremia, or severe pneumonia;
treatment with oral or intravenous antibiotics within 2 weeks prior to the start of
study treatment; patients receiving prophylactic antibiotic therapy (e.g., to prevent
urinary tract infection or exacerbation of COPD) are eligible for this study.

11. Known or suspected active autoimmune disease (congenital or acquired) such as uveitis,
enterocolitis, hepatitis, pituitary inflammation, vasculitis, nephritis, thyroiditis,
etc. (patients with vitiligo, or resolved childhood asthma may be enrolled; patients
with type I diabetes with good insulin control may also be enrolled)

12. Known allogeneic organ transplantation (except corneal transplantation) or allogeneic
hematopoietic stem cell transplantation.