ThymomaPhase 2NCT01364727
A Phase 2 Study of Amrubicin in Relapsed or Refractory Thymic Malignancies
A Phase 2 study testing Amrubicin in people with Thymoma and Thymus Cancer, run by Heather Wakelee at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thymoma, Thymus Cancer, Thymic Carcinoma
- What is being tested?
- Amrubicin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 2 sitesUnited States
- Study dates
- Jun 2011to 31 Dec 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Indiana University
Indianapolis, Indiana, 46202
Stanford University School of Medicine
Stanford, California, 94305
About this study
Official title: 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.
Read the 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
- Being tested
- Amrubicin
- Medical subject headings
- Thymoma, Thymus Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmrubicinDrug
Also called Calsed
35 mg/m2; IV on days 1-3 each 3 week cycle
| Study group | Role | What they receive |
|---|---|---|
| Amrubicin | Experimental | Amrubicin 35mg/m2 IV days 1-3 every 3 weeks Receives: Drug: Amrubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 years
Secondary outcomes (2)
Median Progression-free Survival (PFS)
Median Progression-free survival in patients with thymic malignancies treated with amrubicin
Measured: 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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2011 (estimated)
- Study startJun 2011
- Primary completionJul 2014
- Study completion31 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for ThymomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Heather Wakelee
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene
- Responsible party
- Sponsor-investigator, Heather Wakelee, Stanford University
- Investigators
- Heather A. Wakelee, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01364727
- Sponsor's protocol ID
- IRB-20444
- Other IDs
- SU-01142011-7369, THOR0003
- Status last verified
- Apr 2019
- First submitted
- 31 May 2011
- Last updated
- 16 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Amrubicin in Relapsed or Refractory Thymic Malignancies
- ClinicalTrials.gov ID
- NCT01364727
- Acronym / sponsor ID
- IRB-20444
- Conditions
- Thymoma, Thymus Cancer, Thymic Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Heather WakeleeUniversity, hospital or other
- Collaborators
- Celgene
- Study start
- Jun 2011 (actual)
- Primary completion
- Jul 2014 (actual)
- Study completion
- 31 Dec 2018 (actual)
- First posted
- 2 Jun 2011 (estimated)
- Results
- Posted 14 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Amrubicin | Experimental | Drug: AmrubicinAmrubicin 35mg/m2 IV days 1-3 every 3 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AmrubicinAlso: Calsed35 mg/m2; IV on days 1-3 each 3 week cycle | Drug | Amrubicin |
Primary outcome
Overall Response Rate (ORR)
Time frame: 2 years
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 secondary outcomes
Median Progression-free Survival (PFS)
Time frame: 2 years
Disease Control Rate (DCR)
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Heather A. Wakelee principal investigator
Stanford University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Amrubicin in people with Thymoma and Thymus Cancer, run by Heather Wakelee at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (ORR) (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2019.