Iscador® P immunotherapy for recurrent osteogenic sarcoma

MISTOSUS: Iscador® P (Mistletoe) Immunotherapy To Improve Event Free Survival In Patients With Relapsed Osteosarcoma After Resection Of Pulmonary Metastases

This study is testing if a mistletoe extract called Iscador® P can help people with recurrent osteogenic sarcoma feel better after surgery by giving them regular injections.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: 8 Years to 30 Years
• Sex: All
• Sponsor: Hackensack Meridian Health (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 2 sites (Hackensack, New Jersey and 1 other locations)
• Trial ID: NCT05726383 on ClinicalTrials.gov

What this trial studies

This phase II, single-arm study investigates the use of Iscador® P, a mistletoe extract, in patients with recurrent osteogenic sarcoma who have undergone surgical resection of pulmonary metastases. Participants will receive subcutaneous injections of Iscador® P three times a week, starting with a low dose and gradually increasing based on tolerance. The study aims to monitor disease relapse through CT imaging after treatment. The goal is to evaluate the efficacy and safety of this immunotherapy approach in this specific patient population.

Who should consider this trial

Good fit: Ideal candidates are patients aged 8 to 30 years with a histologically confirmed diagnosis of osteosarcoma and at least one episode of lung relapse following surgical resection.

Not a fit: Patients who have not undergone surgical resection of all gross metastatic disease or those with positive microscopic margins may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new immunotherapy option for patients with recurrent osteogenic sarcoma, potentially improving their outcomes.

How similar studies have performed: While the use of Iscador® P has been licensed in several countries for treating solid tumors, this specific application in recurrent osteogenic sarcoma is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

* 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

  1. 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
  2. Absolute neutrophil count ≥ 500/dL
  3. Platelet count ≥ 20,000/L
  4. Creatinine ≤ 1.5 X the ULN or measurement of calculated creatinine clearance (CrCl) ≥ 60 ml/minute

Exclusion Criteria:

* History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator, including, but not limited to:

  * Another known malignancy other than osteosarcoma that is progressing or requires active treatment.
  * Any prior history of other cancer within the prior 5 years with the exception of adequately treated basal cell carcinoma or cervical intraepithelial neoplasia \[CIN\]/cervical carcinoma in situ or melanoma in situ).
  * Active infection requiring systemic therapy.
  * Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  * New recurrence of osteosarcoma metastasis in any location other than lung
* Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
* Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study drug.
* Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
* Known active hepatitis B (e.g., hepatitis B surface antigen-reactive) or hepatitis C (e.g., hepatitis C virus ribonucleic acid \[qualitative\]). Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody \[HBc Ab\] and absence of HBsAg) are eligible. HBV DNA test must be performed in these patients prior to study treatment. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
* Known history of chronic granulomatous diseases, florid autoimmune diseases, diseases treated with immunosuppressive drugs, hyperthyroidism with tachycardia, tuberculosis, parasitosis or Crohn's disease.
* If female, is pregnant or breastfeeding.
* Patients must have had no systemic chemotherapy or immunotherapy in the three weeks prior to enrollment and must have fully recovered from side effects of prior treatment at enrollment.
* Patients may not receive any additional chemotherapeutic agent (either conventional or experimental) while on study.
* Patients must not have received radiation therapy for up to two weeks prior to enrollment.
* Patients must have no known prior allergy to Iscador® P or any other Viscum album products.
* Patients must not receive concomitant treatment with immunostimulant or immunosuppressive drugs.

Where this trial is running

Hackensack, New Jersey and 1 other locations

• Hackensack University Medical Center — Hackensack, New Jersey, United States (Recruiting)
• M.D. Anderson Children's Cancer Hospital — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Katharine Offer, MD — Hackensack Meridian Health
• Study coordinator: Laura Goode, MS, RN, PCNS-BC

Conditions Osteogenic Sarcoma Recurrent; Osteogenic; Sarcoma; Pulmonary; Metastatic; Immunotherapy; Mistletoe; Bone Tumor