A Phase 2 Study of Amrubicin in Relapsed or Refractory Thymic Malignancies

NCT ID: NCT01364727

Last Updated: 2019-04-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2018-12-31

Brief Summary

A research study of the drug amrubicin in patients with cancer of the thymus (thymoma or thymic carcinoma). We hope to learn whether this drug is an effective and safe treatment for thymic cancers.

Detailed Description

Amrubicin, a synthetic 9-aminoanthracycline, is structurally similar to doxorubicin, but has a different primary mode of action. It acts primarily as an inhibitor of DNA topoisomerase II, exerting its cytotoxic effects by stabilizing a topoisomerase II mediated cleavable complex. This inhibition is significantly more than that seen in doxorubicin, which, in contrast, tends to demonstrate more DNA intercalation than amrubicin.

It has not yet been evaluated for use in thymic malignancies, but given its efficacy in NSCLC and small cell lung cancer (SCLC), as well as the known efficacy of other anthracyclines and topoisomerase II inhibitors in first-line thymoma treatment, it warrants study for use in the second line and beyond in refractory or relapsed patients. Unlike doxorubicin, amrubicin has had minimal cardiotoxicity even with ongoing use, which also makes it a promising agent for use in the second line even for patients who have previously been exposed to, and potentially helped by, doxorubicin.

Conditions

Thymoma; Thymus Cancer; Thymic Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Amrubicin

Amrubicin 35mg/m2 IV days 1-3 every 3 weeks

Group Type: EXPERIMENTAL

Amrubicin

Intervention Type: DRUG

35 mg/m2; IV on days 1-3 each 3 week cycle

Interventions

Amrubicin

35 mg/m2; IV on days 1-3 each 3 week cycle

Intervention Type: DRUG

Other Intervention Names

Calsed

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed invasive or metastatic thymoma or thymic carcinoma. Locally invasive disease is acceptable, provided it is not resectable.
• Previous treatment with at least one prior chemotherapy regimen.
• Documented progressive disease after the most recent chemotherapy regimen.
• Presence of measurable disease on imaging within 4 weeks prior to first dose
• Completion of prior systemic therapy at least 4 weeks prior to first dose.
• Any prior immunotherapy therapy completed at least 8 weeks prior to first dose.
• Any prior surgery completed at least 4 weeks prior to first dose, with adequate recovered from surgery.
• Any prior radiation therapy must have no residual toxic effects of therapy. Chest radiotherapy with curative intent to the primary disease complex must have been completed ≥ 28 days prior to first dose. Cranial radiation must have been completed ≥ 21 days prior to first dose. Radiotherapy to all other areas must have been completed ≥ 7 days prior to first dose.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Leukocytes ≥ 3000/mm³
• Absolute neutrophil count ≥ 1500/mm³
• Platelets ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/d
• Serum bilirubin < 1.5 x institutional upper limit of normal (ULN)
• Aspartate transaminase (AST) and alanine transaminase (ALT) ratio < 3 x ULN
• Serum creatinine < 1.5 times institutional upper limit of normal if serum creatinine above institutional upper limit of normal, calculated serum creatinine clearance by the Cockcroft Gault method > 60 mL/min
• Left ventricular ejection fraction (LVEF) ≥ 50% by transthoracic echocardiogram (TTE) or multiple gated acquisition scan (MUGA)
• For females of childbearing potential, negative serum pregnancy test within 4 weeks of first dose.
• For males and females of childbearing potential, use of effective contraceptive methods during the study.
• Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria

• Current use, or use within 4 weeks prior to first dose, of any other investigational agents.
• Known history of allergic reactions attributed to compounds of similar chemical or biologic composition to amrubicin.
• Active malignancy requiring treatment other than thymic malignancy.
• Pregnant or nursing females due to unknown toxic effects of amrubicin on the developing fetus or in breast milk. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Symptomatic central nervous system metastatic disease. Patients with asymptomatic brain metastases allowed. If treated with surgical resection or radiation therapy, the patient must be stable for >= 2 weeks after completion of therapy. If the patient is on corticosteroids, the dose of corticosteroids, the dose of corticosteroids must have been stable for >= 2 weeks prior to first dose of study treatment, or be in the process of being tapered.
• Concurrent severe or uncontrolled medical disease (including but not limited to active systemic infection, diabetes, hypertension, coronary artery disease, congestive hear failure and mental illness) that in the opinion of the investigator would compromise the safety of the patient or compromise the ability of the patient to complete the study.
• Known history of seropositive human immunodeficiency virus (HIV) or use of immunosuppressive medications for other conditions that would, in the opinion of the investigator, increase the risk of serious neutropenic complications.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: collaborator

Heather Wakelee

OTHER

Sponsor Role: lead

Responsible Party

Heather Wakelee

Professor-Med

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Heather A. Wakelee

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University School of Medicine

Stanford, California, United States

Indiana University

Indianapolis, Indiana, United States

Countries

United States

Other Identifiers

SU-01142011-7369

Identifier Type: OTHER

Identifier Source: secondary_id

THOR0003

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-20444

Identifier Type: -

Identifier Source: org_study_id