Study to evaluate the safety, pharmacokinetics and anti-tumor activity of pixantrone in pediatric patients with cancer

Phase 1

• Conditions: Relapsed or refractory solid tumors (excluding those with CNS tumors) or lymphoma; MedDRA version: 19.0Level: LLTClassification code 10007050Term: CancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-004554-14-Outside-EU/EEA
• Lead Sponsor: CTI BioPharma Corp.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-11-24
• Last Update Posted: 28 November 2016

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

1. Patient and/or guardian have signed an Informed Consent Form and Assent approved by the Institutional Review Board or Institutional Ethics Committee, as appropriate and necessary, on a per-age basis
2. Age 6 months to 21 years old (initial qualifying diagnosis must have been made at or before the age
of 18 and the patient must be under the care of a pediatric hematologist/oncologist)
3. Patient received a diagnosis of lymphoma or any non-hematologic malignancy (except central nervous system [CNS] tumors) for which the patient is considered relapsed or refractory. (NOTE: CNS metastases are allowable in patients who are deemed not at risk for progression during the first 30 days, who are neurologically stable, and, if on corticosteroids, have been on a stable corticosteroid dose for at least 2 weeks.) Patients who have >1 malignancy ongoing during screening are not eligible
4. Patient must have one or more of the following treatment statuses:
• Has failed at least 2 prior lines of chemotherapy
• Has no curative chemotherapy treatment option available
• Is not considered a candidate for available chemotherapy treatment options
5. In dose-escalation accrual, patients may have un-measurable disease (such as bone marrow/bone involvement or diffuse tumors)
6. In dose-escalation accrual, patients may have un-measurable disease in cases where the standard of care would indicate the need for adjuvant chemotherapy after definitive surgery or radiation, but for whom no standard chemotherapy options are available
7. In expansion cohort accrual, patients must have disease that is evaluable or measurable for response and progression per standard criteria for their diagnosis (Refer to the Appendices: RECIST 1.1 Criteria for Evaluation of Solid Tumors, Including Neuroblastoma, Appendix 18.4], Evaluation of Neuroblastoma [Appendix 18.6], and the Lymphoma Staging and Disease Response Criteria [Appendix 18.5])
8. Karnofsky-Lansky performance status (as per age of patient) =50 (Appendix 18.1)
9. Patient must have one or more of the following cardiac function measurements by echocardiogram:
• Left ventricular ejection fraction (LVEF) =55%
• Left ventricular shortening fraction (LVSF) =27%
10. Hemoglobin =8 g/dL (can be post-transfusion)
11. Platelet count =75 × 109/L
12. Absolute neutrophil count (ANC) =0.75 × 109/L
13. Serum direct/conjugated bilirubin =1.5 × upper limit of normal (ULN); patients with clinically diagnosed Gilbert's syndrome and total bilirubin =5 × ULN may be enrolled
14. Aspartate aminotransferase (AST; also called serum glutamicoxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT; also called serum glutamic-pyruvic transaminase [SGPT]) =2.5 × ULN, or =5 × ULN if elevation is due to hepatic involvement by tumor
15. Serum creatinine =2 × ULN
16. Patients must meet the following criteria with respect to prior cancer therapy, radiotherapy, and
stem cell transplants:
a.Myelosuppressive chemotherapy: At least 3 weeks must have elapsed since the completion of myelosuppressive chemotherapy (4 weeks if prior nitrosourea) and resolution of all nonhematologic toxicities to = grade 1.
b.Biologic (anti-neoplastic agent):
• Oral tyrosine kinase inhibitors or other similar agents. At least 7 days must have elapsed since the completion of therapy with a biologic agent and all non-hematologic toxicities must have resolved to =grade 1 prior to enrollment
• Anti-IGFR-1R and other monoclonal antibodies: the shorter

Exclusion Criteria

1. Investigator-predicted life expectancy of less than two months
2. Investigator-predicted inability to tolerate pixantrone monotherapy
treatment adverse effects for less than two months
3. Prior anthracycline treatment with a cumulative dose exceeding 450
mg/m2 (calculated based on doxorubicin equivalents; Appendix 18.3)
4. Active National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) =grade 3 infection, or a lower grade infection deemed resistant or refractory to available antimicrobial agents, or infection requiring ongoing antibiotic treatment
5. Major surgery =7 days and/or with incomplete/inadequate wound healing prior to start of study
treatment
6. Known acute or chronic hepatitis B or hepatitis C virus infection
7. Known seropositivity for human immunodeficiency virus (HIV)
8. Any experimental/investigational therapy =28 days prior to start of
study treatment
9. Myocardial infarction within the past 6 months
10. New York Heart Association class II, III or IV heart failure
11. Any contraindication, known allergy, or hypersensitivity to any
investigational drug(s)
12. Pregnant or lactating
13. Planned radiotherapy or surgical procedures for the qualifying malignancy
14. Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study procedures or followup schedules
15. Other severe and/or uncontrolled medical disease that could compromise participation in the study, or any medical or psychiatric condition that, in the opinion of the investigator, would make pixantrone administration hazardous or obscure the interpretation of data

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified