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

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

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.

Study Overview

• Status: Completed
• Conditions: Thymic Carcinoma; Thymoma; Thymus Cancer
• Intervention / Treatment: Drug: Amrubicin

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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Amrubicin; Amrubicin 35mg/m2 IV days 1-3 every 3 weeks	Drug: Amrubicin; 35 mg/m2; IV on days 1-3 each 3 week cycle; Other Names: Calsed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Participants received amrubicin 35 mg/m2 IV days 1 to 3, every 3 weeks, until progression or toxicity. Tumor response rate was assessed radiographically by the Response Evaluation Criteria In Solid Tumors (RECIST), and the overall response rate (ORR) was expressed as the sum of the Complete Response (CR) rate and the Partial Response (PR) rate. RECIST criteria define when cancer patients improve ("respond"); stay the same ("stable"); or worsen ("progression") during treatments. The criteria presume that linear measures are an adequate substitute for 2-dimensional (2D) methods and includes 4 response categories: CR = Disappearance of all target lesions; PR = 30% decrease in the sum of the longest diameter of target lesions; Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions; Stable disease (SD) = Small changes that do not meet above criteria	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Progression-free Survival (PFS)	Median Progression-free survival in patients with thymic malignancies treated with amrubicin	2 years
Disease Control Rate (DCR)	Disease control rate (DCR) is the sum of Complete Response (CR) rate + Partial Response (PR) rate + Stable Disease (SD) rate , and is expressed here as the sum of the Overall Response Rate (ORR = CR + PR) plus the Stable Disease (SD) rate, ORR + SD. Response was assessed by the RECIST criteria, elaborated above.	2 years

Collaborators and Investigators

• Sponsor: Heather Wakelee
• Collaborators: Celgene

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2011
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): December 31, 2018

Study Registration Dates

• First Submitted: May 31, 2011
• First Submitted That Met QC Criteria: May 31, 2011
• First Posted (Estimate): June 2, 2011

Study Record Updates

• Last Update Posted (Actual): April 16, 2019
• Last Update Submitted That Met QC Criteria: April 5, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Lymphatic Diseases; Neoplasms by Site; Thoracic Neoplasms; Neoplasms, Complex and Mixed; Thymoma; Thymus Neoplasms; Antineoplastic Agents; Amrubicin
• Other Study ID Numbers: IRB-20444; SU-01142011-7369 (Other Identifier: Stanford University); THOR0003 (Other Identifier: OnCore)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No