Local Radiotherapy in Combination With Immunotherapy in Advanced Solid Tumors Patients
Study Details
Study Description
Brief Summary
This is a phase II study to observe efficacy of combining local radiotherapy with PD-1blockade in patients with advanced solid tumors. All patients will accept at least one site of radiotherapy together with PD-1 blockade. The study will evaluate changes of unirradiated and irradiated lesions.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment arm Local irradiation + immunotherapy |
Drug: PD-1 blocking antibody
All patients with more than one distant metastatic lesions will accept at least one site of radiotherapy and PD-1 blockade at the same time.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Objective response rate [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed at least 4 weeks]
The proportion of patients with a tumor volume reduction of 30% lasting for at least 4 weeks，and is the sum of the proportion of complete remission (CR) and partial remission (PR)
- non-irradiated lesion control rate(NRCR) [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months]
The percentage of non-irradiated target lesions with CR/PR or SD
Secondary Outcome Measures
- Progression free survival [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months]
The time from enrollment to disease progression or death from any cause
- Overall survival [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months]
The time from enrollment to death from any cause
- Rate of side effects [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months]
≥ grade 3 adverse effects
Eligibility Criteria
Criteria
Inclusion Criteria:
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Adult patients 18-75 years old with the right to make medical decisions
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Signed informed consent form
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ECOG score of 0-2
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Clear pathological diagnosis of the primary site
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Multiple distant metastases
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Stable assessment of brain metastases after treatment can be enrolled (more than 6 weeks)
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Bone metastases combined with soft tissue mass formation can be enrolled
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imaging with ≥ 2 clearly assessable lesions (bone metastases alone without soft tissue mass formation, brain metastases not as target lesions)
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expected survival ≥ 6 months
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Progression after ≥ 1 prior line of therapy regimen with no standard treatment regimen or intolerable toxicities, including all three of the following:
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Patients must have failed to respond to at least one prior standard of care regimen
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The patient must not have a conventional treatment option that is clinically proven to provide long-term control of the disease and the patient refuses other conventional treatment options
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The patient is intolerant to the toxic side effects of the standard treatment regimen
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No prior immunotherapy history
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Time to last systemic therapy (including monoclonal antibodies) ≥ 4 weeks
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Previous radiotherapy to non-target sites with other evaluable lesions can be enrolled
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Laboratory examination indexes meet the following requirements: WBC ≥ 3×109/L, ANC ≥ 2.0×109/L, PLT ≥ 80×109/L, Hb ≥ 80g/L (according to the normal standards of the central laboratory department); liver function: total bilirubin, ALT and AST are ≤ 1.5xUNL (upper limit of normal value); AST (SGOT)/ALT (SGPT) ≤ 2.5xUNL (upper limit of normal value) ALT (SGPT) ≤ 2.5 x IULN (upper limit of normal value); renal function: Cr≦1.5xUNL (upper limit of normal value), and creatinine clearance rate≧60ml/min; thyroid function T3, T4 within normal range (hypothyroidism can be supplemented with oral thyroxine); cardiac function: cardiac protein three and pro-BNP within normal range, no previous Adrenal function: normal cortisol secretion function or correctable by endocrine assessment
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HBV infected patients with HBV-DNA copy number less than 500 IU/ml
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No history of other malignancies within 5 years (except skin basal cell carcinoma)
Exclusion Criteria:
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Uncontrolled brain metastases (stabilization time <6 weeks)
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Bone metastases alone without clear soft tissue mass formation
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Bone marrow infiltration
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Presence of clinical factors (e.g., bleeding, active infection, or psychiatric factors) that the investigator determines may interfere with the completion of the study process
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Inability to administer radiotherapy due to organ-threatening or other factors as assessed by the investigator
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Patients requiring long-term maintenance steroid therapy (including oral, intravenous use); topical use or inhalation may be included in the study
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Prior autoimmune disease or active disease [e.g., including but not limited to inflammatory bowel disease [IBD], rheumatoid arthritis, autoimmune hepatitis, systemic sclerosis (scleroderma and its variants), systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathy (e.g., Guillain-Barre syndrome)], vitiligo and correctable endocrine deficiencies such as thyroid hypofunction, physiological cortisol hypersecretion may be included in the study and are not considered as exclusion criteria.
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history of active tuberculosis or non-infectious pneumonia or any clinical evidence
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Active viral hepatitis with HBV DNA > 500 IU/ml
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Immunodeficiency syndrome
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comorbid serious medical disorders with concomitant diseases or conditions affecting the normal enrollment of the patient or safety during the study
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previous immunotherapy for other tumors
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History of other malignancies within 5 years (except cured basal cell carcinoma of the skin);
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Pregnant or lactating women;
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Unable or unwilling to sign the informed consent form.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ruijin Hospital, Shanghai Jiaotong University School of Medicine | Shanghai | Shanghai | China | 200025 |
Sponsors and Collaborators
- Ruijin Hospital
Investigators
- Principal Investigator: Jiayi Chen, MD, Ruijin Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RuijinHDR