Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Sunitinib for Advanced Thymus Cancer Following Earlier Treatment

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Collaborator:
Indiana University Simon Cancer Center
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01621568
First received: June 14, 2012
Last updated: July 18, 2014
Last verified: February 2014
  Purpose

Background:

- 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.

Objectives:

- To see if sunitinib is a safe and effective treatment for advanced thymus cancer that has not responded to earlier treatments.

Eligibility:

  • Individuals at least 18 years of age who have advanced thymus cancer that has not responded to earlier treatments.
  • At least one previous cancer treatment must have been chemotherapy treatment containing platinum.

Design:

  • Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies and tumor biopsies will be used to check the severity of the cancer.
  • Participants will take sunitinib tablets once a day, in the morning. They will take the tablets daily for 4 weeks, followed by 2 weeks of rest with no sunitinib. This 6-week period is called a cycle.
  • Treatment will be monitored with frequent blood tests and imaging studies.
  • Treatment cycles may be repeated as long as the tumor does not continue to grow and there are no severe side effects.

Condition Intervention Phase
Thymoma
Thymus Neoplasms
Drug: Sunitinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • To evaluate the objective response rate (PR+CR) for sunitinib in patients with relapsed or refractory thymoma or thymic carcinoma [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the progression-free survival and overall survival for sunitinib in patients with relapsed or refractory thymoma or thymic carcinoma. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • To assess safety and tolerability of sunitinib. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 58
Study Start Date: April 2012
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: April 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Single Group Assignment for Thymoma and Thymic Carcimoma
Drug: Sunitinib
50mg/day for 4 weeks daily, by mouth with 2 weeks off (6 week cycle)

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

3.1.1 Histological confirmation of thymoma or thymic 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.

3.1.4 Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for nonnodal lesions and short axis for nodal lesions) as > 20 mm with conventional techniques or as > 10 mm with spiral CT scan, MRI, or calipers by clinical exam.

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:

  • hemoglobin greater than or equal to 9 g/dL
  • leukocytes greater than or equal to 3,000/mcL
  • absolute neutrophil count greater than or equal to 1,500/mcL
  • platelets greater than or equal to 100,000/mcL
  • total bilirubin within normal institutional limits
  • serum calcium less than or equal to 12.0 mg/dL
  • AST(SGOT)/ALT(SGPT) less than or equal to 2.5 times institutional upper limit of normal
  • creatinine within normal institutional limits

OR

  • creatinine clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with creatinine levels above institutional normal.
  • If subjects have liver metastases, both ALT and AST must be less than or equal to 5 times ULN.
  • Patients must have QTc < 500 msec

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; see Appendix B) cardiac function on baseline ECHO/MUGA:

  • those with a history of Class II heart failure who are asymptomatic on treatment
  • those with prior anthracycline exposure
  • those who have received central thoracic radiation that included the heart in the radiotherapy port.

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 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.

3.1.13 Ability to understand and willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

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

enrolled.

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).

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01621568

Contacts
Contact: Arlene W Berman, R.N. (301) 435-5609 arleneb@mail.nih.gov
Contact: Arun Rajan, M.D. (301) 594-5322 rajana@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    (888) NCI-1937      
Sponsors and Collaborators
Indiana University Simon Cancer Center
Investigators
Principal Investigator: Arun Rajan, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT01621568     History of Changes
Other Study ID Numbers: 120118, 12-C-0118
Study First Received: June 14, 2012
Last Updated: July 18, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
VEGF
Anti-Angiogenesis
Targeted Agent

Additional relevant MeSH terms:
Thymoma
Thymus Neoplasms
Lymphatic Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Complex and Mixed
Thoracic Neoplasms
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014