Trial Title:
Atezolizumab in Combination with Stereotactic Body Radiation Therapy (SBRT) and Surgery for Relapsed Osteosarcoma
NCT ID:
NCT06492954
Condition:
Osteosarcoma
Pulmonary Recurrence of Osteosarcoma
Conditions: Official terms:
Osteosarcoma
Recurrence
Atezolizumab
Conditions: Keywords:
Osteosarcoma
Stereotactic body radiation therapy
Atezolizumab
Pulmonary Recurrence of Osteosarcoma
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Intervention model description:
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.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Surgical Resection
Description:
Removal of all lung nodules, including the radiated nodule, per the standard of care for
osteosarcoma patients with lung metastasis.
Arm group label:
Dose escalation
Intervention type:
Radiation
Intervention name:
Stereotactic Body Radiation Therapy (SBRT)
Description:
Dose level 1: 8 Gy* 3 (Total 24 Gy) Dose level 2: 18 Gy* 3 (Total 54 Gy)
Arm group label:
Dose escalation
Intervention type:
Drug
Intervention name:
Atezolizumab
Description:
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
Arm group label:
Dose escalation
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
Detailed description:
The overall survival at 5 years after recurrence of OS ranges from 16% to 23% in most
studies, highlighting the need for novel treatment approaches. Aggressive surgical
resection is the standard of care for resectable osteosarcoma recurrences limited to the
lung. While previous studies testing immune checkpoint inhibitors (ICIs) in osteosarcoma
have shown limited efficacy, preclinical osteosarcoma studies demonstrate improved
outcomes when ICIs are combined with radiation and administered with minimal residual
disease. The proposed research will be a single-arm, safety pilot evaluating the safety,
tolerability, and preliminary efficacy of Atezolizumab in combination with SBRT and
surgery in patients with resectable, lung-only recurrence of osteosarcoma.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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.
1. Myelosuppressive chemotherapy: ≥ 14 days after the last dose of
myelosuppressive chemotherapy.
2. 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.
3. Biologic (anti-neoplastic) agent: ≥ 7 days after the last dose of a biologic
agent.
4. 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.
5. 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).
6. 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.
7. Autologous Stem Cell Transplant or Rescue: ≥ 6 weeks must have elapsed since
stem cell transplant or rescue.
8. 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.
9. Investigational Agents Not Otherwise Specified: ≥ 28 days must have elapsed
since the last dose of any investigational agent not specified above.
10. Thoracic Surgery or Procedure: ≥ 28 days must have elapsed since prior
thoracotomy, thoracoscopy, or thoracentesis.
- Adequate Bone Marrow Function Defined: Peripheral absolute neutrophil count (ANC) ≥
750/mm3, Platelet count ≥ 50,000/mm3. Must be transfusion independent defined as not
receiving platelet transfusions for at least 7 days before enrollment
- Adequate Renal Function Defined As Creatinine clearance or radioisotope ≥ GFR
70ml/min/1.73 m2
- Adequate Liver Function Defined As Total bilirubin ≤ 1.5 x the upper limit of normal
(ULN) for age, ALT (SGPT) ≤ 3 x the ULN. For this study, the ULN for ALT (SGPT) is
45 U/L.
- Adequate Pancreatic Function Defined As Serum lipase ≤ 1.5 x ULN
- Adequate Thyroid Function Defined As Normal free T4
- Adequate Pulmonary Function Defined As No dyspnea at rest, Pulse oximetry > 92% on
room air
- Adequate Cardiac Function Defined As QTc ≤ 480 msec, Shortening fraction ≥ 27% by
echocardiogram or ejection fraction ≥ 50% by gated radionuclide study or
echocardiogram
- Urine protein: Meets one of the following criteria: (1) urinary protein by urine
dipstick is ≤ 100 mg/dL or ≤ 2+; OR (2) Urine Protein Creatinine (UPC) ratio < 3.5;
OR (3) if 24-hour urine protein was measured, urinary protein ≤ 3500 mg.
- Life expectancy of at least 4 months.
- Negative urine or serum pregnancy test in women of childbearing potential.
- Sexually active patients of reproductive potential are not eligible unless they have
agreed to use an effective contraceptive method for the duration of their study
participation. Patients should maintain adequate contraception for at least 5 months
after the last dose of atezolizumab. Adequate contraception is defined as abstinence
or use of contraceptives with a failure rate of < 1% per year.
- All participants and their parents or legal guardians must sign a written informed
consent and assent (if applicable).
Exclusion Criteria:
- 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).
- Current or prior pneumonitis.
- Live/attenuated vaccine administered within 30 days of enrollment
Gender:
All
Minimum age:
N/A
Maximum age:
50 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Chilldren's Healthcare of Atlanta
Address:
City:
Atlanta
Zip:
30322
Country:
United States
Status:
Recruiting
Contact:
Last name:
Thomas Cash, MD, MSc
Phone:
404-785-0910
Email:
AflacDevTreferral@choa.org
Contact backup:
Last name:
Thomas Cash, MD, MSc
Start date:
October 2024
Completion date:
June 2027
Lead sponsor:
Agency:
Emory University
Agency class:
Other
Collaborator:
Agency:
Genentech, Inc.
Agency class:
Industry
Source:
Emory University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06492954
