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Dinutuximab in Combination With Sargramostim in Treating Patients With Recurrent Osteosarcoma

Information source: National Cancer Institute (NCI)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Metastatic Malignant Neoplasm in the Lung; Metastatic Osteosarcoma; Recurrent Osteosarcoma

Intervention: Dinutuximab (Biological); Laboratory Biomarker Analysis (Other); Pharmacological Study (Other); Sargramostim (Biological)

Phase: Phase 2

Status: Not yet recruiting

Sponsored by: National Cancer Institute (NCI)

Official(s) and/or principal investigator(s):
Pooja Hingorani, Principal Investigator, Affiliation: Children's Oncology Group

Summary

This phase II trial studies how well dinutuximab works when given with sargramostim in treating patients with osteosarcoma that has come back after treatment (recurrent). Dinutuximab is a type of drug called a monoclonal antibody. It is designed to recognize a specific target on the surface of cancer cells. It then attaches to the cancer cells and kills them, without harming normal cells. Sargramostim may help the body increase the amount of of white blood cells it produces, which help the body fight off infections. Giving sargramostim with dinutuximab may help the dinutuximab work better and kill more cancer cells.

Clinical Details

Official title: A Phase II Study of Human-Mouse Chimeric Anti-disialoganglioside Monoclonal Antibody Dinutuximab (ch14.18,NSC# 764038) in Combination With Sargramostim (GM-CSF) in Patients With Recurrent Osteosarcoma

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Disease control

Secondary outcome:

Incidence of UT, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

Pharmacokinetics of dinutuximab

Detailed description: PRIMARY OBJECTIVES: I. To determine the disease control rate in patients with completely resected recurrent osteosarcoma treated with dinutuximab (ch14. 18) in combination with sargramostim (GM-CSF) as compared to historical Children's Oncology Group (COG) experience. SECONDARY OBJECTIVES: I. To characterize the pharmacokinetics of dinutuximab in patients with recurrent osteosarcoma in the proposed administration schedule. II. To determine the occurrence of unacceptable toxicity (UT) in patients with recurrent osteosarcoma treated with dinutuximab in combination with sargramostim. TERTIARY OBJECTIVES: I. To assess the relationship between probability of disease control and tumor GD2 expression. II. To assess killer cell immunoglobulin-like receptor (KIR) and Fcgamma receptor (FcgammaR) genotypes, natural killer cell p30 (NKp30) isoforms and its circulating ligand, B7-H6, and their relationships to the probability of disease control. III. To attempt banking of tumor samples for future research studies from patients enrolled on study who undergo biopsy or resection of suspected metastatic disease recurrence while on protocol therapy or during the evaluation period. IV. To determine a descriptive profile of human anti-chimeric antibody (HACA) during immunotherapy. OUTLINE: Patients receive sargramostim subcutaneously (SC) on days 1-14 and dinutuximab intravenously (IV) over 20 hours on days 4 and 5 (dinutuximab infusion may be extended for an additional 2 days for anticipated toxicities). Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.

Eligibility

Minimum age: N/A. Maximum age: 29 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients must have histologic diagnosis of osteosarcoma at original diagnosis

- Patients must have had at least one episode of disease recurrence in the lungs

without limitation on number of episodes of recurrence as long as they meet the following criteria:

- Surgical resection of all possible sites of suspected pulmonary metastases in

order to achieve a complete remission within 4 weeks prior to study enrollment**

- Pathologic confirmation of metastases from at least one of the resected sites

- For patients with bilateral pulmonary metastases, resection must be

performed from both lungs and the study enrollment must be within 4 weeks from date of the last lung surgery

- Note: post-operative radiographic confirmation of complete remission will not be

required as long as the operating surgeon believes that all sites of disease were resected; patients with positive microscopic margins will be eligible to enroll

- Patient must have adequate tumor specimen available for submission

- Patients must have a performance status corresponding to Eastern Cooperative Oncology

Group (ECOG) scores of 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age

- Patients must have fully recovered from the acute toxic effects of all prior

chemotherapy, immunotherapy, or radiotherapy prior to entering this study

- Myelosuppressive anti-cancer therapy: must not have been received within 2 weeks

of study entry (4 weeks if prior nitrosourea)

- Biologic (anti-neoplastic agent): at least 7 days since the completion of

therapy with a biologic agent

- Radiation therapy (RT): >= 2 weeks for local palliative radiation therapy (RT)

(small port); >= 6 weeks must have elapsed if prior craniospinal RT or if >= 50% radiation of pelvis; >= 6 weeks must have elapsed if other substantial bone marrow (BM) radiation

- Surgery: >= 2 weeks from last major surgery, with the exclusion of a central

line placement and core needle or small open biopsies

- Patient must not have received pegfilgrastim (Neulasta) within 14 days of enrollment

- Patient must not have received filgrastim (G-CSF, Neupogen) within 7 days of

enrollment

- Patient must not have received immune suppressants: corticosteroids (for other than

allergic reactions and anaphylaxis), cyclosporine or tacrolimus within 7 days of enrollment

- Note: the use of topical and/or inhalational steroids is allowed

- Total absolute phagocyte count (APC = [%neutrophils + %monocytes) x white blood cells

[WBC]) is at least 1000/uL

- Platelet count >= 50,000/uL

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70

mL/min/1. 73 m^2 or

- A serum creatinine based on age/gender as follows:

- 1 month to < 6 months: 0. 4 (male) 0. 4 (female)

- 6 months to < 1 year: 0. 5 (male), 0. 5 (female)

- 1 to < 2 years: 0. 6 (male), 0. 6 (female)

- 2 to < 6 years: 0. 8 (male), 0. 8 (female)

- 6 to < 10 years: 1 (male), 1 (female)

- 10 to < 13 years: 1. 2 (male), 1. 2 (female)

- 13 to < 16 years: 1. 5 (male), 1. 4 (female)

- >= 16 years: 1. 7 (male), 1. 4 (female)

- Total bilirubin =< 1. 5 x upper limit of normal (ULN) for age

- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110

U/L (for the purpose of this study, the ULN for SGPT is 45 U/L)

- Serum albumin >= 2 g/dL

- Shortening fraction of >= 27% by echocardiogram, or

- Ejection fraction of >= 50% by radionuclide angiogram or echocardiogram

- No evidence of dyspnea at rest, no history of exercise intolerance, and a pulse

oximetry > 94%

- Patients with a known seizure disorder may be enrolled if on anticonvulsants and/or

well controlled

- Central nervous system (CNS) toxicity including peripheral neuropathy =< grade 2

Exclusion Criteria:

- Patients with distant bone metastases at original diagnosis or relapse (patients with

only skip lesions will be eligible)

- Patients with concurrent local and pulmonary recurrence at the time of enrollment;

note: patients who had local recurrence previously that has been treated and now present with an isolated pulmonary recurrence and meet the surgical resection criteria stated above will be eligible

- Patients with primary refractory disease with progression of the primary tumor on

initial therapy

- Patients with CNS disease involvement at the time of most recent episode of disease

recurrence preceding enrollment

- Patients with a prior hypersensitivity reaction to sargramostim

- Patients who have received prior anti-GD2 therapy, including chimeric antigen

receptor (CAR) T cells directed against GD2 antigen

- Female patients who are pregnant are ineligible

- Lactating females are not eligible unless they have agreed not to breastfeed their

infants

- Female patients of childbearing potential are not eligible unless a negative

pregnancy test result has been obtained

- Sexually active patients of reproductive potential are not eligible unless they have

agreed to use an effective contraceptive method for the duration of their study participation

Locations and Contacts

Children's Oncology Group, Philadelphia, Pennsylvania 19104, United States; Not yet recruiting
Pooja Hingorani, Phone: 602-933-0920, Email: phingorani@phoenixchildrens.com
Pooja Hingorani, Principal Investigator
Additional Information

Starting date: December 2015
Last updated: July 15, 2015

Page last updated: August 23, 2015

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