Atezolizumab in Combination With Stereotactic Body Radiation Therapy (SBRT) and Surgery for Relapsed Osteosarcoma

NCT06492954 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY00007256
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to determine the safety and tolerability of combined Atezolizumab, stereotactic body radiation therapy (SBRT), and surgical resection of pulmonary metastases in patients with pulmonary recurrence of osteosarcoma

Conditions

Osteosarcoma; Pulmonary Recurrence of Osteosarcoma

Keywords

Osteosarcoma; Stereotactic body radiation therapy; Atezolizumab; Pulmonary Recurrence of Osteosarcoma

Outcome Measures

Primary Outcomes (2)

• Number of participants with Dose limiting toxicity at Dose Level 1

  If 6 participants have been enrolled and evaluated, and only 0 or 1 have experienced a DLT, the next participant will be enrolled at Dose Level 2

  Baseline, end of 1 year

• Number of participants with Dose limiting toxicity at Dose Level 2

  If 6 participants have been enrolled and evaluated, and only 0 or 1 have experienced a DLT, enrollment will be terminated, and accrual determined complete.

  Baseline, end of 1 year

Secondary Outcomes (3)

• Disease Control Rate

  Baseline, at 12 months

• Progression-free survival (PFS)

  Baseline, through study completion (an average of 1 year)

• Overall Survival

  Baseline, through study completion (an average of 1 year)

Study Arms (1)

Dose escalation

EXPERIMENTAL

Unilateral: Participants start with atezolizumab, followed ≤ 1 week later by SBRT at the assigned dose for a single lesion. After 2 cycles, those with unilateral disease undergo complete surgical resection, including all lung nodules, including the radiated one, as per osteosarcoma standard care. Atezolizumab resumes 14-28 days post-op, per protocol criteria, barring toxicity or disease progression. Bilateral: Subjects first undergo surgery on the non-SBRT side. 7-14 days later, they start atezolizumab, followed ≤ 1 week later by SBRT on the other lesion. After 2 cycles of atezolizumab, surgery on the contralateral side removes all lung nodules, including the radiated one, per standard care. Atezolizumab resumes 14-18 days post-op, per protocol criteria, barring toxicity or disease progression

Procedure: Surgical Resection; Radiation: Stereotactic Body Radiation Therapy (SBRT); Drug: Atezolizumab

Interventions

Surgical Resection PROCEDURE

Removal of all lung nodules, including the radiated nodule, per the standard of care for osteosarcoma patients with lung metastasis.

Dose escalation

Stereotactic Body Radiation Therapy (SBRT) RADIATION

Dose level 1: 8 Gy\* 3 (Total 24 Gy) Dose level 2: 18 Gy\* 3 (Total 54 Gy)

Dose escalation

Atezolizumab DRUG

For subjects \<18 years of age at the time of enrollment, Atezolizumab will be administered IV on Day 1 of each 21-day cycle at a dose of 15 mg/kg (maximum dose of 1200 mg). Subjects ≥ 18 years old will receive a flat dose of 1200 mg IV on Day 1 of each 21-day cycle

Dose escalation

Eligibility Criteria

• Age: Up to 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participants must have had histologic verification of osteosarcoma at the original diagnosis or relapse
• Participants must be in first or greater relapse of osteosarcoma
• Recurrence must be limited to the lung but can be unilateral or bilateral
• All pulmonary nodules must be resectable as determined by the institutional surgeon. Resectable pulmonary nodules are defined as nodules that can be removed without performing a pneumonectomy (e.g., nodules immediately adjacent to the main stem bronchus or main pulmonary vessels). There is no maximum number of lesions provided the surgeon thinks a complete surgical remission can be achieved.
• Participants must have at least 1 lesion that is ≥ 5 mm and meets the criteria to receive SBRT AND an additional nodule(s) that meets protocol definition for a metastatic nodule necessitating surgical resection: single nodule ≥ 5 mm, or ≥ 2 nodules ≥ 3 mm in size
• Patients must have a Lansky (≤ 16 years) or Karnofsky (\> 16 years) score of ≥ 60, or ECOG performance score of ≤ 2
• All prior treatment-related toxicities must have resolved to ≤ Grade 1 OR be determined clinically stable by the treating investigator.
• Myelosuppressive chemotherapy: ≥ 14 days after the last dose of myelosuppressive chemotherapy.
• Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g., Pegfilgrastim) or 7 days for a short-acting growth factor.
• Biologic (anti-neoplastic) agent: ≥ 7 days after the last dose of a biologic agent.
• Cellular therapy: ≥ 21 days must have elapsed from the last dose of any type of cellular therapy (e.g., modified T cells, NK cells, dendritic cells, etc.) with resolution of any associated toxicities.
• Interleukins, interferons, and cytokines (other than hematopoietic growth factors): ≥ 21 days must have elapsed from the last dose of interleukins, interferon, or cytokines (other than hematopoietic growth factors).
• Antibodies: 7 days or 3 half-lives (whichever is longer) but not longer than 30 days, and toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
• Autologous Stem Cell Transplant or Rescue: ≥ 6 weeks must have elapsed since stem cell transplant or rescue.
• Radiotherapy (XRT): ≥ 14 days after local palliative XRT (small port); ≥ 3 months must have elapsed if prior craniospinal XRT was received, if ≥ 50% of the pelvis was irradiated, or if TBI was received; ≥ 6 weeks must have elapsed if other substantial bone marrow radiation was given.

You may not qualify if:

• Pregnancy or Breast-Feeding
• Active metastatic disease outside of the lungs including bone, CNS, or any extrapulmonary involvement
• \> Grade 1 pleural effusion
• Prior lung radiation
• Active autoimmune disorder that has required systemic treatment in the past 12 months, or a documented history of severe autoimmune disorder, or a syndrome that requires systemic steroids or immunosuppressive agents. Participants with type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, or skin disorders such as vitiligo, psoriasis, or alopecia not requiring systemic treatment may be permitted to enroll.
• Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months before initiation of study treatment, unstable arrhythmia, or unstable angina.
• Prior treatment with an immune checkpoint inhibitor is allowed provided it was not permanently discontinued due to toxicity and was not given with radiation.
• Active tuberculosis
• Any medical condition or illness that would compromise the participants's ability to undergo surgery, cause unacceptable safety risk, or compromise compliance with the protocol.
• Chronic use of immunosuppressive therapies.
• Participants with an uncontrolled infection.
• Subjects who have received prior allogeneic stem cell transplant or solid organ transplant are not eligible.
• Participants who, in the opinion of the investigator, may not be able to comply with the protocol-required procedures.
• Participants who are currently receiving any other investigational or anti-cancer agents.
• Participants with a known history of HIV, hepatitis B, and/or hepatitis C (testing not required as part of screening).

Sponsors & Collaborators

• Genentech, Inc.: collaborator
• Emory University: lead

Study Sites (1)

Chilldren's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Osteosarcoma

Interventions

Radiosurgery; atezolizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Thomas Cash, MD, MSc

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thomas Cash, MD, MSc

CONTACT

404-785-0910; aflacdevtreferral@choa.org

Chloe Edgerton

CONTACT

chloe.edgerton@choa.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: As the optimal SBRT dose needed to generate an immune response in osteosarcoma is unknown, two different SBRT doses will be tested: * Dose Level 1: 8 Gy x 3 * Dose Level 2:18 Gy x 3 * Participants will receive the appropriate pediatric \[\<18 years: 15 mg/kg (max dose: 1200 mg)\] or adult (≥ 18 years: 1200 mg) recommended phase 2 dose of Atezolizumab IV q3 weeks. The investigator will enroll 6 patients on each dose level, safety permitting, to maximize the information gained about each regimen. * Patients will undergo surgical resection of all lung nodules * If ≤ 1/6 patients treated at dose level 1 experience dose-limiting toxicity (DLT), dose-escalation will proceed to dose level 2 where an additional 3-6 patients will be enrolled. * If ≥ 2/6 patients treated at dose level 1 experience DLT, enrollment to the trial will close pending further evaluation of subjects treated and consideration will be given to a protocol amendment to modify the therapeutic approach.

Study Record Dates

• First Submitted: June 21, 2024
• First Posted: July 9, 2024
• Study Start: March 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: March 2, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)