Sunitinib for Advanced Thymus Cancer Following Earlier Treatment
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|ClinicalTrials.gov Identifier: NCT01621568|
Recruitment Status : Active, not recruiting
First Posted : June 18, 2012
Last Update Posted : July 8, 2019
|First Submitted Date ICMJE||June 14, 2012|
|First Posted Date ICMJE||June 18, 2012|
|Last Update Posted Date||July 8, 2019|
|Study Start Date ICMJE||April 18, 2012|
|Estimated Primary Completion Date||April 30, 2020 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||To evaluate the objective response rate (PR+CR) for sunitinib in patients with relapsed or refractory thymoma or thymic carcinoma [ Time Frame: 2 years ]
Objective response rate (CR + PR) will be measured according to RECIST 1.1 criteria for sunitinib monotherapy in patients with advanced thymic malignancies.
|Original Primary Outcome Measures ICMJE
||To evaluate the objective response rate (PR+CR) for sunitinib in patients with relapsed or refractory thymoma or thymic carcinoma [ Time Frame: 2 years ]|
|Change History||Complete list of historical versions of study NCT01621568 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Sunitinib for Advanced Thymus Cancer Following Earlier Treatment|
|Official Title ICMJE||A Phase II Study of Sunitinib in Patients With Advanced Relapsed or Refractory Thymoma or Thymic Carcinoma With at Least One Prior Line of Platinum-Based Systemic Chemotherapy|
- Sunitinib is drug that is approved for treating various types of cancers, including kidney cancers. However, it has not been approved to treat cancers of the thymus. Sunitinib works by blocking proteins that are responsible for cell division and growth. Some of these proteins can be found on thymus cancer cells. Researchers want to see if sunitinib can be used to treat advanced thymus cancer. It will be given to people who have had at least one earlier chemotherapy treatment containing platinum.
- To see if sunitinib is a safe and effective treatment for advanced thymus cancer that has not responded to earlier treatments.
Platinum-based chemotherapy is the standard of care for advanced unresectable thymoma and thymic carcinoma. However over 50% of these patients may fail initial therapy and therefore require second-line therapy. New therapeutic options are needed for patients who have disease progression on or after platinum-containing therapy. Results obtained from protocol 12-C-0118 so far have shown impressive clinical activity of sunitinib in patients with recurrent thymic carcinoma with an objective response rate of 23% and disease control rate of 91% which is unprecedented for this histology. Treatment at a dose of 50 mg once daily for four weeks followed by 2 weeks off was poorly tolerated. Twenty five out of 41 patients needed dose reductions due to development of intolerable adverse events.
- To evaluate the objective response rate (PR+CR) for sunitinib in patients with relapsed or refractory thymoma or thymic carcinoma
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 2|
|Study Design ICMJE||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Intervention ICMJE||Drug: Sunitinib
50mg/day for 4 weeks daily, by mouth with 2 weeks off (6 week cycle)
|Study Arms ICMJE||Experimental: Arm 1
Single Group Assignment for Thymoma and Thymic Carcimoma
Intervention: Drug: Sunitinib
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Active, not recruiting|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Estimated Study Completion Date ICMJE||April 30, 2020|
|Estimated Primary Completion Date||April 30, 2020 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
3.1.1Histological confirmation of thymoma (Group 1 only) orthymic carcinoma by the pathology department/CCR/NCI or the pathology department of participating institutions.
3.1.2 At least one prior line of platinum-based chemotherapy or patient must have refused cytotoxic chemotherapy. Progressive disease must be documented prior to study entry.
3.1.3 Patients must not have received chemotherapy, radiation therapy, or undergone major surgery within 4 weeks prior to enrollment.
3.1.4Patients must have measurable disease, per RECIST 1.1
3.1.5 Age greater than or equal to 18 years.
3.1.6 ECOG performance status less than or equal to 2 (Karnofsky > 50 percent)
3.1.7 Life expectancy of greater than 3 months.
3.1.8 Patients must have normal organ and marrow function as defined below:
3.1.9 PT or INR, and APTT less than or equal to 1.5 times upper limit of normal (ULN), unless the abnormality can be explained by the presence of lupus anticoagulant or if these values are in the therapeutic range for a patient on low molecular weight heparin.
3.1.10 The following groups of patients are eligible provided they have New York Heart Association Class II (NYHA) cardiac function on baseline ECHO/MUGA:
3.1.11 Patients must have blood pressure (BP) no greater than 140 mmHg (systolic) and 90 mmHg (diastolic) for eligibility. Initiation or adjustment of BP medication is permitted prior to study entry provided that the average of three BP readings at a visit prior to
enrollment is less than 140/90 mmHg.
3.1.12 Absence of brain metastases as confirmed by imaging of the brain by MRI or CT brain with contrast performed at baseline screening
3.1.13 The effects of sunitinib on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because anti-angiogenic agents are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. All women of childbearing potential must have a negative pregnancy test prior to receiving sunitinib. Should a woman
become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of sunitinib administration.
3.1.14 Ability to understand and willingness to sign a written informed consent document.
3.2.1 Patients with tumor amenable to potentially curative therapy.
3.2.2 Prior treatment within the past 6 months with sunitinib, sorafenib, bevacizumab or other multikinase inhibitors targeting any of the following: vascular endothelial growth factors 1 3 (VEGF1 3), FMS-like tyrosine kinase 3 (FLT3), stem cell growth factor (c-KIT), platelet-derived growth factors-alpha and -beta (PDGF-alpha,-beta), colony-stimulating factor 1 (CSF1), and the RET receptor for glial-derived neurotrophic factors.
3.2.3 Patients with symptomatic brain metastases will be excluded from trial secondary to poor prognosis. However, patients who have had treatment for their brain metastasis and whose brain disease has remained stable for 3 months without steroid therapy may be
3.2.4 Patients with evidence of severe or uncontrolled systemic disease, or any concurrent condition, which could compromise participation in the study, including, but not limited to, active or uncontrolled infection, immune deficiencies, uncontrolled HBV and/or HCV infection unless sustained virologic response to HCV therapy, uncontrolled diabetes,serious non-healing ulcer, wound or bone fracture, history of intra-abdominal abscess, abdominal fistula or gastrointestinal perforation within 28 days of treatment, history of
pulmonary embolism in the past 12 months, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within 12 months prior to study entry, Class III or IV heart failure as defined by the NYHA functional classification system,stroke/cerebrovascular accident or transient ischemic attack within the past 12 months or psychiatric illness/social situations which would jeopardize compliance with the protocol.
3.2.5 History of a previous invasive malignancy within the last 5 years, except adequately treated non-melanoma skin cancer, papillary carcinoma of the thyroid or carcinoma in situ of the uterine cervix.
3.2.6 Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
3.2.7 Patients who are receiving any other investigational agents.
3.2.8 History of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib. Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. (A list of potent CYP3A4 inducers or inhibitors can be found in Section 5.2.) An exception will be made for patients who are on ritonavir-based highly active antiretroviral therapy, in which case the starting dose of sunitinib will be modified as indicated in Sections 5.1.1 and 5.2.12. Every effort should be made to switch patients taking such agents or substances to other medications. A comprehensive list of medications and substances known or with the potential to alter the pharmacokinetics of sunitinib through CYP3A4 is provided.
3.2.9 Pregnant women are excluded from this study because sunitinib angiogenesis inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the
mother with sunitinib breastfeeding should be discontinued if the mother is treated with sunitinib.
3.2.10 Patients who require therapeutic doses of Coumadin derivative anticoagulants such as warfarin are excluded. Low molecular weight heparin is permitted, provided the patient s PT/INR is less than or equal to 1.5. Coumadin doses of up to 2 mg daily are permitted for prophylaxis of thrombosis.
3.2.11 Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid function in the normal range with medication are ineligible.
3.2.12 Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain sunitinib tablets are excluded.
3.2.13 Patients with QTc prolongation (defined as a QTc interval equal to or greater than 500 msec) or other significant ECG abnormalities are excluded.
3.2.14 Patients with poorly controlled hypertension (systolic blood pressure of 140 mmHg or higher or diastolic blood pressure of 91 mmHg or higher) are ineligible.
3.2.15 Patients who require use of therapeutic doses of coumarin derivative anticoagulants such as warfarin are excluded, although doses of up to 2 mg daily are permitted for prophylaxis of thrombosis. Note: Low molecular weight heparin is permitted provided the patient s PT INR is less than or equal to 1.5.
3.2.16 Patients with HIV infection are eligible provided their CD4 count is greater than or equal to the institutional LLN ( greater than or equal to 334 cells/uL).
|Ages ICMJE||18 Years to 100 Years (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT01621568|
|Other Study ID Numbers ICMJE||120118
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )|
|Study Sponsor ICMJE||National Cancer Institute (NCI)|
|Collaborators ICMJE||Indiana University School of Medicine|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||May 14, 2019|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP