| Eligibility |
Inclusion Criteria:
- 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
1. Between 12 years of age and 39 years of age at the time the Informed Consent/ Assent
form is signed.
2. Weight at least 40 kg. Diagnosis
3. Has histologic confirmation of osteosarcoma at diagnosis.
4. 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:
1. Surgical resection of all possible sites of suspected pulmonary metastases to
achieve a complete remission within 8 weeks prior to study enrollment
2. Pathological confirmation of osteosarcoma from at least one resected tumor.
3. 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
5. 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
6. 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
7. 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.
8. 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 :
9. A female patient is eligible to participate if she is not pregnant, not breastfeeding,
and at least one of the following conditions applies:
1. Not a woman of childbearing potential (WOCBP) as defined in the protocol OR
2. 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.
10. 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:
11. 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.
Exclusion Criteria:
1. Has clinically evident metastatic or recurrent disease.
2. Has concurrent pulmonary recurrence and local recurrence at the primary tumor site.
3. Has primary refractory disease with progression of the primary tumor on
initial-therapy.
4. Has CNS or any extrapulmonary disease involvement at the time of the most recent
episode of disease recurrence proceeding enrollment.
5. Has active infection requiring systemic therapy or is dependent on or is currently
receiving systemic antibiotics that cannot be discontinued before dosing. (Note:
Patients who discontinue an antibiotic prior to dosing must wait at least 5 half-lives
after the last dose of antibiotic before receiving any OST31-164 infusion). Inhaled
prophylactic PJP (pneumocystis jiroveci pneumonia) treatment is acceptable per
Investigator discretion.
6. Is currently dependent on or has received corticosteroids within the past 4 weeks
(topical corticosteroids and occasional inhaled corticosteroids are allowed).
7. Is currently participating in or has participated in a study of an investigational
agent or is using an investigational device within 4 weeks of the first dose of
treatment.
8. Has a history of other active malignancy for < 2 years prior to enrollment. Basal cell
carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer
that has undergone potentially curative therapy or is felt by the Investigator to be
at low risk for recurrence is allowed.
9. Has an active autoimmune disease requiring systemic treatment within the past 3 months
or a documented history of clinically severe autoimmune disease, or a syndrome that
requires systemic steroids or immunosuppressive agents. Replacement therapy (e.g.,
thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or
pituitary insufficiency) is not considered a form of systemic treatment. Patients with
vitiligo or resolved childhood asthma/atopy would be an exception to this rule.
Patients who require intermittent use of bronchodilators or local steroid injections
will not be excluded from the study. Patients with hypothyroidism stable on hormone
replacement or Sjogren's syndrome will not be excluded from the study.
10. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
11. Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the trial, starting with the pre-screening or screening visit
through 120 days after the last dose of study treatment.
12. Has a known allergy to any component of the study treatment(s) formulations.
13. Has a contraindication (e.g., sensitivity/allergy) to both trimethoprim/
sulfamethoxazole and amoxicillin.
14. Has contraindication to administration of NSAIDs.
15. Is currently receiving or will be receiving any chemotherapy, including PI3K
inhibitors, during the treatment phase.
16. Has had a prior monoclonal antibody therapy within 2 weeks prior to study Day 1.
17. Requires or anticipates requiring tumor necrosis factor (TNF) blocking agent (e.g.,
infliximab) therapy for diagnosis of rheumatologic disease or inflammatory bowel
disease (e.g., ankylosing spondylitis, Crohn's disease, plaque psoriasis, psoriatic
arthritis, rheumatoid arthritis, or ulcerative colitis).
18. Has previous history of listeriosis.
19. Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
20. Has known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA
[qualitative] is detected).
21. Has received a live vaccine within 30 days prior to Study Day 1.
22. Patient is or has an immediate family member (spouse, children, or parent) who is
directly involved with this study or is employed by the investigational site or
Sponsor, unless prospective Institutional Review Board (IRB) approval (by chair or
designee) is given allowing exception to this criterion for a specific patient.
Regulatory Requirements:
1. All patients and/or their parents or legal guardians must sign a written informed
consent.
2. All institutional, FDA, and NCI requirements for human studies must be met.
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