MISTOSUS: Iscador® P (Mistletoe) Immunotherapy To Improve Event Free Survival In Patients With Relapsed Osteosarcoma After Resection Of Pulmonary Metastases
This will be a phase II, single arm study of osteosarcoma patients with fully resected pulmonary metastases. The MTD corresponds to the dosage recommendations of the manufacturer of Iscador® P which is licensed in Sweden, New Zealand, South Korea, Germany and Switzerland for the treatment of solid tumors and precancerous lesions. The study population includes patients with relapse of osteosarcoma in the lung following surgical resection of all gross disease (2nd or greater CR). Following completion of final thoracotomy, they will be treated with Iscador® P at concentrations up to the MTD with surveillance imaging via CT scan to monitor for relapsed disease.
• Histologic diagnosis of osteosarcoma.
• Patients with at least one episode of relapse in the lung (without limitation of number of episodes), following surgical resection of all gross metastatic disease.
• Surgical resection of all possible sites of suspected pulmonary metastases in order to achieve a complete remission within 8 weeks prior to study enrollment. Note: If surgery related changes such as atelectasis are seen on the post-operative CT scan, patients will remain eligible to enroll as long as the operating surgeon believes that all sites of metastases were resected. Patients with positive microscopic margins will be eligible to enroll.
• Pathological confirmation of metastases from at least one of the resected sites.
• Age ≥ 8 years of age and \<30 years of age.
• Patients must be able to receive subcutaneous injections.
• Performance level as measured by Karnofsky ≥60% for patients \> 16 years of age or Lansky ≥ 60% for patients ≤ 16 years of age.
• Female patients of childbearing potential must have a negative serum blood pregnancy test during screening and a negative urine pregnancy test within 3 days prior to receiving the first dose of study drug. If the screening serum test is done within 3 days prior to receiving the first dose of study drug, a urine test is not required. If a patient is of childbearing potential the patient must agree to use effective contraception during the study and for 120 days after the last dose of study drug.
• If male, agrees to use an adequate method of contraception starting with the first dose of study drug through 120 days after the last dose of study drug
• Life expectancy of \> two months
• Experienced resolution of toxic effect(s) of the most recent prior anti-cancer therapy to Grade \<1 (except alopecia, cytopenia, or neuropathy). If a patient underwent major surgery or radiation therapy of \>30 Gy, they must have recovered from the toxicity and/or complications from the intervention.
• Patients must meet the following laboratory criteria
‣ Adequate hepatic function with serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 times the upper limit of normal (ULN) and total serum bilirubin \< 2.5 times the ULN or Direct bilirubin ≤ ULN for patients with total bilirubin levels \> 2.5 X ULN
⁃ Absolute neutrophil count ≥ 500/dL
⁃ Platelet count ≥ 20,000/L
⁃ Creatinine ≤ 1.5 X the ULN or measurement of calculated creatinine clearance (CrCl) ≥ 60 ml/minute