VX15/2503 in Treating Younger Patients With Recurrent, Relapsed, or Refractory Solid Tumors

Refractory Malignant Solid Neoplasm Clinical Trial

Official title:

A Phase 1/2 Trial of VX15/2503 in Children, Adolescents, or Young Adults With Recurrent or Relapsed Solid Tumors

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03205644
• Other study ID #: ADVL1614
• Secondary ID: NCI-2017-01103AD
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• First received: June 29, 2017
• Last updated: June 29, 2017
• Start date: May 5, 2018
• Est. completion date: October 2021

Study information

• Verified date: June 2017
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase I/II trial studies the side effects and best dose of anti-SEMA4D monoclonal antibody VX15/2503 (VX15/2503) and to see how well it works in treating younger patients with solid tumors that have come back after treatment, or do not respond to treatment. Monoclonal antibodies, such as VX15/2503, may interfere with the ability of tumor cells to grow and spread.

Description:

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) and/or recommended Phase 2 dose of VX15/2503 administered as an intravenous infusion every 14 days to children with recurrent or refractory solid tumors. (Part A) II. To define and describe the toxicities of VX15/2503 administered on this schedule. (Parts A-B) III. To characterize the pharmacokinetics of VX15/2503 in children with recurrent or refractory cancer. (Parts A-B) IV. To preliminarily define the antitumor activity of VX15/2503 for the treatment of relapsed or refractory osteosarcoma. (Part B) V. To determine if VX15/2503 either improves the disease control rate at 4 months in patients with recurrent measurable osteosarcoma or produces an objective response rate in patients with relapsed or refractory osteosarcoma.

SECONDARY OBJECTIVES:

I. To assess the pharmacodynamics of VX15/2503 through VX15/2503 saturation of T-lymphocytes.

II. To assess the immunogenicity of VX15/2503 in pediatric patients with recurrent or refractory cancer.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive VX15/2503 intravenously (IV) over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 75
• Est. completion date: October 2021
• Est. primary completion date: September 19, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Months to 30 Years

Eligibility

Inclusion Criteria:

• Parts A: Patients with recurrent or refractory solid tumors are eligible, excluding central nervous system (CNS) tumors; patients must have had histologic verification of malignancy at original diagnosis or relapse

• Part B: Patients with recurrent or refractory osteosarcoma are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse

• Parts A: Patients must have either measurable or evaluable disease

• Part B: Patients must have measurable disease

• Patient?s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life

• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score

• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately

• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive

• >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)

• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent

• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1

• Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid

• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator

• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)

• Stem cell Infusions (with or without total body irradiation [TBI]):

• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)

• Autologous stem cell infusion including boost infusion: >= 42 days

• Cellular Therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)

• Radiation Therapy (XRT)/External Beam Irradiation including Protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation

• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy

• Patients must not have received prior exposure to VX15/2503

• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3

• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)

• Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts above (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity; at least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study; if dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity

• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70ml/min/1.73 m^2 or

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

• Age: 1 to < 2 years; Male: 0.6 mg/dL; Female: 0.6 mg/dL

• Age: 2 to < 6 years; Male: 0.8 mg/dL; Female: 0.8 mg/dL

• Age: 6 to < 10 years; Male: 1 mg/dL; Female: 1 mg/dL

• Age: 10 to < 13 years; Male: 1.2 mg/dL; Female: 1.2 mg/dL

• Age: 13 to < 16 years; Male: 1.5 mg/dL; Female: 1.4 mg/dL

• Age: >= 16 years; Male: 1.7 mg/dL; Female: 1.4 mg/dL

• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age

• Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L

• Serum albumin >= 2 g/dL

• Pulse oximetry > 94% on room air if there is clinical indication for determination (e.g. dyspnea at rest)

• All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines

• Tissue blocks or slides must be sent; if tissue blocks or slides are unavailable, the study chair must be notified prior to enrollment

Exclusion Criteria:

• Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy

• Patients receiving systemic corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of systemic corticosteroid; Note: patients who are using topical or inhaled corticosteroids are eligible

• Patients who are currently receiving another investigational drug are not eligible

• Patients who are currently receiving other anti-cancer agents are not eligible (except leukemia patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy)

• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial

• Patients who have an uncontrolled infection are not eligible

• Patients who have received a prior solid organ transplantation are not eligible

• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

Related Conditions & MeSH terms

• Neoplasms
• Osteosarcoma
• Recurrent Malignant Solid Neoplasm
• Recurrent Osteosarcoma
• Refractory Malignant Solid Neoplasm

Intervention

Biological:
• Anti-SEMA4D Monoclonal Antibody VX15/2503
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Pharmacological Study
Correlative studies

Locations

Country	Name	City	State
United States	COG Phase I Consortium	Arcadia	California

Sponsors (3)

Lead Sponsor	Collaborator
Children's Oncology Group	COG Phase I Consortium, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacokinetics of VX15/2503 in serum (Parts A-B)	Will be summarized with simple summary statistics.	Prior to, at the end of, and 2 hours following infusion on day 1 of courses 1-2; days 4 & 8 of course 1; prior to and the end of infusion on day 15 of course 1; prior to infusion on day 1 of course 2; prior to start of infusion on day 1 of courses 3+
Primary	Disease control rate (Part B)	Disease control success will be defined as complete response, partial response or stable disease.	At 4 months
Primary	Incidence of toxicities of VX15/2503 (Parts A-B)	Will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	Up to 3 years
Primary	Maximum tolerated dose (MTD) and/or recommended phase 2 dose of VX15/2503 (Part A)	Will be defined as the maximum dose at which fewer than one-third of patients experience dose limiting toxicities (DLT) and graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	Up to 28 days
Primary	Response (complete response [CR] or partial response [PR]) (Part B)	Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.	Up to 3 years
Secondary	Immunogenicity of VX15/2503	Will be assessed in serum through a qualified enzyme-linked immunosorbent assay (ELISA). Analyses will be descriptive and exploratory and hypotheses generating in nature.	Up to 3 years
Secondary	Pharmacodynamics of VX15/2503 defined as VX15/2503 saturation of T-lymphocytes	Will be assessed in blood and will utilize a validated flow-cytometry based assay. Analyses will be descriptive and exploratory and hypotheses generating in nature.	Up to 3 years