AOST1421: Combination Drug Therapy to Treat Patients with Recurrent Osteosarcoma

A Phase II Study of Human-Mouse Chimeric Anti-Disialoganglioside Monoclonal Antibody ch14.18 (Dinutuximab) in Combination with Sargramostim (GM-CSF) in Patients with Recurrent Osteosarcoma

Categories:

Solid Tumor

Phase I/II

Diseases Treated:

Osteosarcoma

Eligibility Overview:

  • Younger than 30 years old
  • Original diagnosis of osteosarcoma
  • Osteosarcoma has come back in the lungs after original treatment
  • Lung tumors have been removed surgically within the last 4 weeks before enrolling in the study
  1. Brief Summary

    Patients with recurrent osteosarcoma have an overall survival of less than 30% at 5 years. Limited treatment options exist for these patients, with surgery remaining the mainstay of therapy at recurrence. The majority of patients who achieve a second or subsequent complete surgical remission will recur.

    GD2 is a cell surface disialoganglioside that is ubiquitously expressed on osteosarcoma tumor cells and therefore is a rational therapeutic target. Historical experience from neuroblastoma (NB) trials shows that anti-GD2 based therapy works best in the setting of minimal residual disease. Therefore, we propose to evaluate the effects of ch14.18 (dinutuximab), an anti-GD2 antibody, in combination with sargramostim (GM-CSF) in patients with pulmonary recurrence of osteosarcoma that are able to achieve a complete surgical resection.

    Primary Objective

    The main objective of the study is to determine how well ch14.18 works in combination with sargramostim in patients with recurrent osteosarcoma.

    Eligibility Criteria

    • Younger than 30 years old
    • Original diagnosis of osteosarcoma
    • At least one episode of disease recurrence in the lungs
    • Surgical resection of all possible sites of suspected pulmonary metastases in order to achieve a complete remission with 4 weeks prior to study enrollment
    • Pathologic confirmation of metastases from at least one of the resected sites
    • Performance status corresponding to ECOG scores of 0, 1 or 2
    • Recovered from toxic effects of prior therapy
    • Adequate hematological, rental, liver, cardiac, pulmonary and CNS function

    Exclusion Criteria include:

    • Distant bone metastases at original diagnosis or relapse (Patients with only skip lesions are eligible.)
    • Concurrent local and pulmonary recurrence at time of enrollment
    • Primary refractory disease with progression of the primary tumor on initial therapy
    • CNS disease
    • Prior hypersensitivity reaction to sargramostim
    • Prior anti-GD2 therapy

    Study Design

    Interventional, Phase II

    Study Sites

    St. Jude Children’s Research Hospital
    Memphis, Tennessee

    Collaborating sites in and outside the U.S.

  2. About this study

    Osteosarcoma is the most common type of bone cancer in children and teens. Treatment usually includes chemotherapy, surgery and/or radiation therapy. In some patients, however, the disease comes back after treatment. This is called recurrent or relapsed osteosarcoma. When osteosarcoma comes back, it usually appears in the lungs.

    Recurrent osteosarcoma is difficult to treat. The most common treatments are chemotherapy alone or in combination with a second surgery.

    Purpose of this observational study

    This study will test a new drug therapy in children, adolescents and young adults with osteosarcoma that has come back in the form of lung tumors. Researchers want to know if this combination of two drugs will stop recurrent osteosarcoma from coming back after treatment. They also want to find out if this drug combination is safe and learn how well it is handled by the body.

    The experimental drug combination includes two drugs:

    • Ch14.18 is also known as dinutuximab. It is designed to target cancer cells without harming healthy cells. Some studies have shown that it can help kill cancer cells in certain types of childhood cancer, such as neuroblastoma. The drug has been approved by the U.S. Food and Drug Administration as a treatment for children with high-risk neuroblastoma. It has not been approved to treat recurrent osteosarcoma.
    • Sargramostim is also known as GM-CSF or leukine. It is a man-made version of a protein that the body normally produces to encourage white blood cells to grow. White blood cells help the body fight off infection.  Sargramostim has been approved by the FDA for some cancer treatments but not for osteosarcoma.

    Eligibility overview

    • Younger than 30 years old
    • Original diagnosis of osteosarcoma
    • Osteosarcoma has come back in the lungs after original treatment
    • Lung tumors have been removed surgically within the last 4 weeks before enrolling in the study
  3. AOST1421 Quick View
    Sponsor National Cancer Institute
    Clinicaltrials.gov identifier NCT02484443
    Trial start date November 2015
    Estimated enrollment 44
    Study type Interventional
    Conditions Osteosarcoma
    Ages
    Younger than 30 years old
    Principal investigator Michael Bishop, MD
    Study site St. Jude Children’s Research Hospital
    For a consultation or to discuss AOST1421 St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org

Contact

Michael Bishop, MD

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334
Email: referralinfo@stjude.org

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.