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Note: Patients enrolled on AOST2031 are eligible for enrollment in the present study |
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Patients are eligible to be included in the study only if all the following |
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criteria apply |
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Age and Weight |
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Between 12 years of age and 39 years of age at the time the Informed Consent/ Assent form is signed |
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Weight at least 40 kg. Diagnosis |
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Has histologic confirmation of osteosarcoma at diagnosis |
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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 |
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Surgical resection of all possible sites of suspected pulmonary metastases to achieve a complete remission within 8 weeks prior to study enrollment |
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Pathological confirmation of osteosarcoma from at least one resected tumor |
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Patients with no clinical evidence of osteosarcoma at the time of resection will not require radiographic confirmation of complete remission for enrollment Note: The definition of complete resection is: gross resection of all disease as per the operating surgeon. (For further details see |
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<https://members.childrensoncologygroup.org/files/Disc/surgery/handbooks/OsteoBoneHandb> |
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ook.pdf) Performance Status |
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Patient must have a performance status corresponding to ECOG scores of 0, 1, or 2. Use |
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Karnofsky scale for patients > 16 years of age and Lansky scale for patients < years |
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of age Prior Therapy |
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Patient must have fully recovered from the acute toxic effects of all prior |
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chemotherapy, immunotherapy, radiotherapy, or surgery prior to entering this study |
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Organ Function Requirements |
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Patient has adequate organ function as defined below |
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a. Hematological: i. Absolute neutrophil count (ANC) is at least 1,000/µL without |
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transfusion or growth factor support. ii. Platelet count ≥ 50,000/µL without |
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Maximum Serum Creatinine (mg/dL) |
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transfusion or growth factor support. b. Adequate renal function defined as: i |
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Creatine clearance or radioisotope glomerular filtration rate (GFR) > 70 mL/min/1.73 |
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m2 or ii. A serum creatine based on age/gender as follows |
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Age: 12 to < 13 years Male :1.2 Female:1.2 Age:13 to < 16 years Male :1.5 Female:1.4 |
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Age: ≥ 16 years Male :1.7 Female:1.4 Note: the threshold for creatinine values in this |
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table were derived from the Schwartz formula for estimating GFR |
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c. Adequate liver function defined as: i. Total bilirubin < 1.5 x upper limit of |
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normal (ULN) for age ii. Serum glutamic-pyruvic transaminase (SGPT) / alanine |
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aminotransferase (ALT) < 110 U/L (for the purpose of this study the ULN for SGPT is 45 |
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U/L) iii. Serum albumin > 2 g/dL |
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d. Adequate coagulation i. International normalized ratio (INR) or prothrombin time |
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(PT) < 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or |
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ii. Activated partial thromboplastin time (aPTT) < 1.5 x ULN unless patient is |
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INR is within therapeutic range of intended use of anticoagulants |
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receiving anticoagulant therapy as long as aPTT is within therapeutic range of |
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intended use of anticoagulants |
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e. Adequate cardiac function defined as: i. Shortening fraction of > 27% by |
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echocardiogram, or ii. Ejection fraction of > 50% by radionuclide angiogram or |
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echocardiogram f. Adequate pulmonary function defined as: i. No evidence of dyspnea at |
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rest, no history of exercise intolerance, and a pulse oximetry of > 94% |
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g. Central nervous system (CNS) function defined as: i. Patients with a known seizure |
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disorder may be enrolled if on anticonvulsants and/or are well-controlled |
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ii. CNS toxicity including peripheral neuropathy < Grade 2 |
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Patient and/or patient's parent or legal guardian must be capable of understanding the |
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investigational nature, potential risks, and benefits of the study. The patient and/or |
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the parent or legal guardian must sign a written informed consent. Age-appropriate |
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assent will be obtained per institutional guidelines |
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Contraception |
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A female patient is eligible to participate if she is not pregnant, not breastfeeding |
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Female patients |
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and at least one of the following conditions applies |
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A WOCBP who agrees to follow the contraceptive guidance in the protocol during |
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Not a woman of childbearing potential (WOCBP) as defined in the protocol OR |
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the treatment period and for at least 120 days after the last dose of study |
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treatment |
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A female patient of childbearing potential must have a negative urine or serum |
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Male patients |
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pregnancy test within 72 hours prior to receiving any dose of study treatment. If the |
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urine test is positive or cannot be confirmed as negative, a serum pregnancy test will |
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be required |
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A male patient is eligible to participate if he agrees to follow the contraceptive |
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guidance in the protocol during the study treatment period and for at least 120 days |
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after the last dose of study treatment |
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Has clinically evident metastatic or recurrent disease
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Has concurrent pulmonary recurrence and local recurrence at the primary tumor site
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Has primary refractory disease with progression of the primary tumor on
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initial-therapy
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Has CNS or any extrapulmonary disease involvement at the time of the most recent
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episode of disease recurrence proceeding enrollment
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Has active infection requiring systemic therapy or is dependent on or is currently
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receiving systemic antibiotics that cannot be discontinued before dosing. (Note
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Has a known allergy to any component of the study treatment(s) formulations
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Patients who discontinue an antibiotic prior to dosing must wait at least 5 half-lives
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after the last dose of antibiotic before receiving any OST31-164 infusion). Inhaled
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Has contraindication to administration of NSAIDs
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prophylactic PJP (pneumocystis jiroveci pneumonia) treatment is acceptable per
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Investigator discretion
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Has had a prior monoclonal antibody therapy within 2 weeks prior to study Day 1
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Is currently dependent on or has received corticosteroids within the past 4 weeks
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(topical corticosteroids and occasional inhaled corticosteroids are allowed)
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Has previous history of listeriosis
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Is currently participating in or has participated in a study of an investigational
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Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
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agent or is using an investigational device within 4 weeks of the first dose of
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treatment
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Has received a live vaccine within 30 days prior to Study Day 1
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Has a history of other active malignancy for < 2 years prior to enrollment. Basal cell
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carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer
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Regulatory Requirements
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that has undergone potentially curative therapy or is felt by the Investigator to be
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at low risk for recurrence is allowed
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All institutional, FDA, and NCI requirements for human studies must be met
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Has an active autoimmune disease requiring systemic treatment within the past 3 months
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or a documented history of clinically severe autoimmune disease, or a syndrome that
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requires systemic steroids or immunosuppressive agents. Replacement therapy (e.g
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thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or
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pituitary insufficiency) is not considered a form of systemic treatment. Patients with
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vitiligo or resolved childhood asthma/atopy would be an exception to this rule
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Patients who require intermittent use of bronchodilators or local steroid injections
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will not be excluded from the study. Patients with hypothyroidism stable on hormone
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replacement or Sjogren's syndrome will not be excluded from the study
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Has known psychiatric or substance abuse disorders that would interfere with
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cooperation with the requirements of the trial
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Is pregnant or breastfeeding or expecting to conceive or father children within the
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projected duration of the trial, starting with the pre-screening or screening visit
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through 120 days after the last dose of study treatment
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Has a contraindication (e.g., sensitivity/allergy) to both trimethoprim
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sulfamethoxazole and amoxicillin
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Is currently receiving or will be receiving any chemotherapy, including PI3K
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inhibitors, during the treatment phase
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Requires or anticipates requiring tumor necrosis factor (TNF) blocking agent (e.g
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infliximab) therapy for diagnosis of rheumatologic disease or inflammatory bowel
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disease (e.g., ankylosing spondylitis, Crohn's disease, plaque psoriasis, psoriatic
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arthritis, rheumatoid arthritis, or ulcerative colitis)
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Has known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA
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[qualitative] is detected)
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Patient is or has an immediate family member (spouse, children, or parent) who is
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directly involved with this study or is employed by the investigational site or
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Sponsor, unless prospective Institutional Review Board (IRB) approval (by chair or
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designee) is given allowing exception to this criterion for a specific patient
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All patients and/or their parents or legal guardians must sign a written informed
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consent
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