Summary

Up to 45 Patients aged 12 to 39 with osteosarcoma (bone cancer) that had recurred in the
lungs and has recently been surgically removed will be enrolled. Patients will receive
OST31-164 infusions every 3 weeks over 48 weeks and be followed after that for 3 years.

Objectives

This is a Phase 2, open-label, multicenter, single-arm study in patients (12-39 years) with a
recent history of pulmonary recurrent osteosarcoma that has been completely resected. Planned
enrollment is a maximum of 45 patients who will receive OST31-164 as a single agent every 3
weeks for 48 weeks with 4 doses constituting 1 treatment cycle (12 weeks per cycle). Each
patient will receive treatment at a dose of 1x109 CFU until week 48 or until disease
progression, unacceptable toxicity, or the patient meets any other treatment discontinuation
criteria. Following treatment discontinuation, all patients will enter a 3-year survival
follow-up period. Exploratory evaluation of immune response will be conducted. If available,
tissue from the recent resection will be sent to the COG Biobank for future genomic and
pathologic analysis by the COG.

Eligibility

1. Note: Patients enrolled on AOST2031 are eligible for enrollment in the present study. Patients are eligible to be included in the study only if all the following criteria apply: Age and Weight
2. Between 12 years of age and 39 years of age at the time the Informed Consent/ Assent form is signed.
3. Weight at least 40 kg. Diagnosis
4. Has histologic confirmation of osteosarcoma at diagnosis.
5. Has at least one episode of disease recurrence in the lungs without limitation on the number of episodes of recurrence as long as the following criteria are met:
6. Surgical resection of all possible sites of suspected pulmonary metastases to achieve a complete remission within 8 weeks prior to study enrollment
7. Pathological confirmation of osteosarcoma from at least one resected tumor.
8. Patients will not require radiographic confirmation of complete remission for enrollment. However, a postoperative CT chest scan is required as a baseline for future comparisons. https://members.childrensoncologygroup.org/files/Disc/surgery/handbooks/OsteoBoneHandb ook.pdf) Performance Status
9. Patient must have a performance status corresponding to ECOG scores of 0, 1, or 2. Use Karnofsky scale for patients > 16 years of age and Lansky scale for patients < years of age Prior Therapy
10. Patient must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, radiotherapy, or surgery prior to entering this study. Organ Function Requirements
11. Patient has adequate organ function as defined below: a. Hematological: i. Absolute neutrophil count (ANC) is at least 1,000/µL without transfusion or growth factor support. ii. Platelet count = 50,000/µL without transfusion or growth factor support. b. Adequate renal function defined as: i. Creatine clearance or radioisotope glomerular filtration rate (GFR) > 70 mL/min/1.73 m2 or ii. A serum creatine based on age/gender as follows: Maximum Serum Creatinine (mg/dL) Age: 12 to < 13 years Male :1.2 Female:1.2 Age:13 to < 16 years Male :1.5 Female:1.4 Age: = 16 years Male :1.7 Female:1.4 Note: the threshold for creatinine values in this table were derived from the Schwartz formula for estimating GFR. c. Adequate liver function defined as: i. Total bilirubin < 1.5 x upper limit of normal (ULN) for age ii. Serum glutamic-pyruvic transaminase (SGPT) / alanine aminotransferase (ALT) < 110 U/L (for the purpose of this study the ULN for SGPT is 45 U/L) iii. Serum albumin > 2 g/dL d. Adequate coagulation i. International normalized ratio (INR) or prothrombin time (PT) < 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or INR is within therapeutic range of intended use of anticoagulants. ii. Activated partial thromboplastin time (aPTT) < 1.5 x ULN unless patient is receiving anticoagulant therapy as long as aPTT is within therapeutic range of intended use of anticoagulants. e. Adequate cardiac function defined as: i. Shortening fraction of > 27% by echocardiogram, or ii. Ejection fraction of > 50% by radionuclide angiogram or echocardiogram f. Adequate pulmonary function defined as: i. No evidence of dyspnea at rest, no history of exercise intolerance, and a pulse oximetry of > 94%. g. Central nervous system (CNS) function defined as: i. Patients with a known seizure disorder may be enrolled if on anticonvulsants and/or are well-controlled. ii. CNS toxicity including peripheral neuropathy < Grade 2.
12. Patient and/or patient's parent or legal guardian must be capable of understanding the investigational nature, potential risks, and benefits of the study. The patient and/or the parent or legal guardian must sign a written informed consent. Age-appropriate assent will be obtained per institutional guidelines. Contraception: Female patients :
13. A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
14. Not a woman of childbearing potential (WOCBP) as defined in the protocol OR
15. A WOCBP who agrees to follow the contraceptive guidance in the protocol during the treatment period and for at least 120 days after the last dose of study treatment.
16. A female patient of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving any dose of study treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Male patients:
17. A male patient is eligible to participate if he agrees to follow the contraceptive guidance in the protocol during the study treatment period and for at least 120 days after the last dose of study treatment.