Pulmonary Resectable Osteosarcoma Treated by Metastasectomy and Pre-operative Immunotherapy and Stereotactic Body Radiotherapy (PROMIS): a Prospective Clinical Trial

NCT06114225 | Recruiting Phase 2 DMC

• 1 other identifier: 2023-LLS-221
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to evaluate the efficacy and safety of pre-operative concurrent Stereotactic Body Radiotherapy (SBRT) and and programmed cell death protein-1 (PD-1) blockade immunotherapy followed by surgical metastasectomy for resectable metastatic osteosarcoma.

Conditions

Osteosarcoma

Keywords

neoadjuvant immunotherapy; metastasectomy; osteosarcoma; pulmonary metastasis

Outcome Measures

Primary Outcomes (1)

• 12-month progression-free survival rate (12m-PFSR)

  The proportion of patients that are progression-free according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), defined as the ratio of patients who have not died or progressed (CR+PR+SD) over the total number of subjects recruited.

  12 months from recruitment

Secondary Outcomes (8)

• Objective response rate (ORR)

  From baseline to disease progression, death or the time of metastasectomy, whichever occurs first, up to 3 years after accrual

• Disease control rate (DCR)

  From baseline to disease progression, death or the time of metastasectomy, whichever occurs first, up to 3 years after accrual

• Progression-free survival (PFS)

  From baseline to disease progression or death, whichever occurs first, up to 3 years after accrual

• Overall survival (OS)

  From baseline until the reported death of the patients due to any causes, up to 3 years after accrual

• Quality of life assessed by patient-reported outcomes (PROs)

  From baseline until the reported death of the patients due to any causes, up to 3 years after accrual

Other Outcomes (3)

• Exploratory outcome: progression-free survival(PFS) in different subgroups

  From baseline to disease progression or death, whichever occurs first, up to 3 years after accrual.

• Exploratory outcome: the molecular analysis of tumor sample in correlation with the oncological outcome

  From baseline to disease progression or death, whichever occurs first, up to 3 years after accrual.

• Exploratory outcome: the expression of immune infiltration biomarker of tumor sample in correlation with the oncological outcome.

  From baseline to disease progression or death, whichever occurs first, up to 3 years after accrual.

Study Arms (1)

treatment arm

EXPERIMENTAL

The participant receive metastasectomy, immunotherapy and Stereotactic Body Radiotherapy (SBRT)

Combination Product: metastasectomy and pre-operative immunotherapy (gemcitabine and penpulimab ) and stereotactic body radiotherapy

Interventions

metastasectomy and pre-operative immunotherapy (gemcitabine and penpulimab ) and stereotactic body radiotherapy COMBINATION_PRODUCT

participants first receive concurrent SBRT and penpulimab (PD-1 blockade) and two cycles of GP regimen (gemcitabine d1,d8 and Penpulimab d8 per a 21-day cycle), followed by complete pulmonary metastasectomy. After surgery, participant receive another 4 cycles of GP regimens followed by Penpulimab monotherapy maintenance. The rationale is that pre-operative SBRT could boost the immune microenvironment, leading to a long-term effect of immunotherapy post-metastasectomy and eventually resulting in better long-term survivorship compared to the histological control for pulmonary resectable recurrence of osteosarcoma .

treatment arm

Eligibility Criteria

• Age: 10 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent signed before any trial-related procedures are carried out.
• Histologically confirmed osteosarcoma, with a diagnosis of pulmonary metastases without the existence of local recurrence (previous re-resection of local recurrence with wide margin is allowed).
• Resectable pulmonary nodule(s), defined as nodule(s) that are removable by wedge resection/ segmentectomy/lobectomy without necessitating a total pneumonectomy (e.g., nodules immediately adjacent to the main stem bronchus or main pulmonary vessels), and no evidences of malignant pleural effusion.
• Participants have received at least one standardized systemic treatment regimen at the time of enrollment, and have not received gemcitabine in the past.
• Patient has adequate pulmonary function eligible for one-staged or two-staged thoracic surgery.
• Aged no less than 10 years old and no more than 65 years old;
• For patients ≥16 years old, ECOG score is between 0 and 2 (for patients with amputations, if they can basically take care of themselves and can move freely for more than 50% of their waking hours with the assistance of stretchers, walkers, wheelchairs, etc.) still included);
• For patients under 16 years old, Lansky score is at least 70 or above (for patients with amputations who are unable to participate in active recreational activities due to amputation, if they can participate in most active recreational activities with the assistance of walkers, wheelchairs, etc., they are still eligible included).
• The expected survival time is greater than 24 weeks;
• The majority of the recurrent lesions with an established radiological diagnosis could receive SBRT;
• Major organ functions meet basic safety standards within 7-14 days before treatment.
• Women of childbearing age should agree that they must use contraceptive measures (such as intrauterine devices, birth control pills or condoms) during the study and within 6 months after the end of the study; if in doubt, serum or urine tests within 7 days before study enrollment The pregnancy test is negative and the patient must be non-lactating; the male should agree that contraceptive measures must be used during the study period and within 6 months after the end of the study period;
• If there are recurrent lesions previously treated by surgery, radiofrequency ablation or radiotherapy:
• If the image of the metastatic lesion is stable, enrollment is allowed and SBRT is not required for that lesion;
• If the metastatic lesion has image progression, if it was previously treated with surgery and SBRT can be performed, enrollment is allowed; if it was previously treated with radiofrequency ablation or radiotherapy, if repeat SBRT can be considered, enrollment is still allowed.

You may not qualify if:

• Diagnosed with malignant diseases other than tumors within 5 years before the first dose;
• Currently participating in interventional clinical research treatment, or have received other research drugs or used research equipment within 4 weeks before the first dose;
• Previously received the following therapies: anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs or drugs targeting another stimulating or synergistic inhibition of T cell receptors (e.g., CTLA-4, OX-40, CD137) drug and secondary resistance to the drug (i.e., the best efficacy evaluation is CR, PR or SD lasting more than 4 months, but secondary tumor resistance develops after treatment).
• Received systemic systemic treatment with Chinese patent medicines with anti-tumor indications or drugs with immunomodulatory effects (including thymosin, interferon, interleukin, except local use to control pleural effusion) within 2 weeks before the first dose;
• Active autoimmune disease requiring systemic treatment (such as use of disease-modifying drugs, glucocorticoids, or immunosuppressants) within 2 years before the first dose. Replacement therapies (such as thyroxine, insulin, or physiological glucocorticoids for adrenal or pituitary insufficiency, etc.) are not considered systemic treatments;
• Are receiving systemic glucocorticoid treatment (excluding nasal spray, inhaled or other route of topical glucocorticoids) or any other form of immunosuppressive therapy within 7 days before the first dose of the study;
• Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
• Known to be allergic to any components of monoclonal antibody preparations (have experienced grade 3 or above allergic reactions);
• Have not fully recovered from toxicity and/or complications caused by any intervention before initiating treatment (i.e., ≤Grade 1 or reaching baseline, excluding fatigue or alopecia);
• Known history of human immunodeficiency virus (HIV) infection (i.e. HIV1/2 antibody positive);
• Get live vaccine within 30 days before the first dose (cycle 1, day 1);
• Pregnant or lactating women;
• Any serious or uncontrollable systemic disease

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine

Shanghai, Shanghai Municipality, 20025, China

RECRUITING

MeSH Terms

Conditions

Osteosarcoma

Interventions

Metastasectomy; Gemcitabine; penpulimab; Radiosurgery

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Investigative Techniques

Study Officials

• Weibin Zhang, PhD, MD

  Ruijin Hospital

  PRINCIPAL INVESTIGATOR

• Yuhui Shen, PhD, MD

  Ruijin Hospital

  PRINCIPAL INVESTIGATOR

• Qiyuan Bao, PhD, MD

  Ruijin Hospital

  PRINCIPAL INVESTIGATOR

• Junxiang Wen, PhD, MD

  Ruijin Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Weibin Zhang, PhD, MD

CONTACT

+8613501824630; zhangweibin10368@163.com

Yuhui Shen, PhD, MD

CONTACT

+8613918209875; yuhuiss@163.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: Chief director of the orthopaedics department, Vice director of the orthpaedic research institute of Shanghai Jiaotong University

Study Record Dates

• First Submitted: October 3, 2023
• First Posted: November 2, 2023
• Study Start: June 1, 2023
• Primary Completion (Estimated): September 15, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: November 2, 2023

Record last verified: 2023-10

Locations

CN (1)