Osteosarcoma Clinical Trials

∙ Diagnosis:

∙ Participants must have had histologic verification of osteosarcoma at original diagnosis or relapse.

• All participants with relapsed or refractory osteosarcoma are eligible, provided they received front-line treatment with a regimen that contained at least 3 of the following agents: methotrexate, doxorubicin, cisplatin, and ifosfamide

⁃ Disease Status:

• Dose Escalation: Participants must have either measurable or evaluable disease per RECIST.Note: Participants with no evidence of disease on imaging (e.g., following pulmonary metastasectomy) are not eligible during the dose escalation phase.

• Dose Expansion: Participants with measurable or evaluable disease per RECIST and those with no evidence of disease on imaging following pulmonary metastasectomy are eligible during the dose expansion phase.

⁃ Performance Level: Participants must have a Lansky (≤ 16 years) or Karnofsky (\> 16 years) score of ≥ 60, or Eastern Cooperative Oncology Group (ECOG) ≤ 2 Note: Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory to assess the performance score.

⁃ Prior Therapy: Participants must have fully recovered from the clinically significant acute effects of all prior anti-cancer chemotherapy, immunotherapy, surgery, or radiation therapy before enrollment.

• Myelosuppressive chemotherapy: ≥ 14 days after the last dose.

• Hematopoietic growth factors: ≥ 14 days after a long-acting growth factor (e.g., pegfilgrastim) or ≥ 7 days for a short-acting growth factor. For agents with known delayed adverse events, extend recovery period accordingly.

• Biologic (anti-neoplastic) agent: ≥ 7 days after the last dose. Extend period if adverse events occur beyond 7 days.

• Cellular therapy: ≥ 21 days since last dose (e.g., modified T cells, gamma-delta T cells, natural killer (NK) cells, dendritic cells) with recovery from associated toxicities.

• Interleukins, interferons, and cytokines (excluding hematopoietic growth factors): ≥ 21 days since last dose.

• Antibodies: 7 days or 3 half-lives (whichever is longer), up to 30 days. Toxicity must be resolved to Grade ≤ 1.

• Radiation therapy (XRT):

‣ 14 days after local palliative XRT (small port)

⁃ 150 days after radiation to ≥ 50% of pelvis or bone marrow

⁃ 6 weeks after substantial bone marrow radiation

∙ Prior use of Nucleoside Analogue (Gemcitabine): Allowed. Investigational agents not otherwise specified: ≥ 30 days since last dose. Surgery: ≥ 2 weeks since last major surgery, including pulmonary metastasectomy (central line placement and core/small open biopsies are excluded)

∙ Organ Function Requirements:

• Adequate Bone Marrow Function Defined As:

‣ Peripheral absolute neutrophil count (ANC) ≥ 750/mm3 (0.75x109/L)

⁃ Platelet count ≥ 75,000/mm3 (75x109/L)

• Adequate Renal Function Defined As: Creatinine clearance or radioisotope GFR ≥ 70 ml/min/1.73 m2

• Adequate Liver Function Defined As:

‣ Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x the upper limit of normal (ULN) for age

⁃ ALT ≤ 5 x the ULN

• Adequate Pulmonary Function Defined As: No dyspnea at rest, no exercise intolerance, and no oxygen requirement (pulse oximetry \> 93% on room air).

• Adequate Cardiac Function Defined As: QTc ≤ 470 ms using Fridericia formula