A Phase II Study of Single Agent Intravenous (IV) VEGF Trap in Patients With Poor Prognostic Recurrent and/or Metastatic Thyroid Cancer After RAI Therapy
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 41
- Locations
- 1
- Primary Endpoint
- Progression-free Survival to Determine the 6-month Progression-free-survival (PFS) Rate
Study Overview
Brief Summary
This phase II trial is studying how well aflibercept works in treating patients with recurrent and/or metastatic thyroid cancer that has not responded to radioactive iodine therapy. Aflibercept may stop the growth of tumor cells by blocking blood flow to the tumor and by carrying tumor-killing substances directly to thyroid cancer cells.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the radiographic response rate (by RECIST criteria) of IV VEGF Trap after four cycles (approximately 8 weeks) of therapy, as well as the 6-month progression-free-survival (PFS) rate (as part of a composite primary outcome measure), in patients with recurrent and/or metastatic differentiated thyroid carcinoma of follicular cell origin (D-TC-FCO; comprising papillary, follicular, Hurthle cell, and respective variants) not amenable to RAI or curative surgery.
SECONDARY OBJECTIVES:
I. To determine the safety and toxicity profile of IV VEGF Trap in patients with recurrent and/or metastatic TC-FCO. Please see the adverse event table for the specifics for this protocol.
II. To determine the biologic effect of IV VEGF Trap on FDG avidity after four cycles (approximately 8 weeks) of therapy through pre- and post-treatment FDG-PET scans in patients with recurrent and/or metastatic D-TC-FCO.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histopathologically confirmed differentiated thyroid carcinoma of follicular cell origin, including any of the following histologies and their respective variants:
- •Papillary
- •Follicular
- •Hürthle cell
- •Must have surgically inoperable and/or recurrent or metastatic disease
- •At least one fludeoxyglucose F 18 (FDG)-PET-avid lesion, defined as any focus of increased FDG uptake > normal mediastinal activity with standard uptake variable (SUV) maximum levels ≥ 3, as documented by baseline PET scan
- •Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
- •Progressive disease, defined by ≥ 1 of the following occurring during or after prior treatment (e.g., radioactive isotope [RAI] treatment):
- •Presence of new or progressive lesions on CT scan or MRI
- •New lesions on bone scan or PET scan
- •Rising thyroglobulin level documented by a minimum of 3 consecutive rises, with an interval of > 1 week between each determination
- •No known history of brain metastasis
- •ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- •ANC ≥ 1,500/mcL
- •Platelet count ≥ 75,000/mcL
- •WBC ≥ 3,000/mcL
- •Total bilirubin ≤ 1.5 times upper limit of normal(ULN)
- •AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN for liver metastases)
- •Creatinine ≤ 1.5 times ULNOR creatinine clearance ≥ 60 mL/min
- •INR ≤ 1.2 (≤ 1.5 times ULN if on prophylactic-dose anticoagulation)
- •Urine protein: creatinine ratio < 1 OR 24-hour urine protein < 500 mg
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for ≥ 6 months after completion of study therapy
- •Documentation of systolic blood pressure ≤150 mm Hg and diastolic blood pressure ≤100 mm Hg
- •No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
- •No history of allergic reactions attributed to compounds of similar chemical or biologic composition to other agents used in the study
- •No serious or non-healing wound, ulcer, or bone fracture
- •No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess in the past 28 days
- •No significant traumatic injury within the past 28 days
- •No clinically significant cardiovascular disease, defined as any of the following:
- •Cerebrovascular accident within the past 6 months
- •Myocardial infarction within the past 6 months
- •Coronary artery bypass grafting or unstable angina within the past 6 months
- •NYHA grade III-IV congestive heart failure
- •Canadian Cardiovascular Class grade III or greater angina within the past 6 months
- •Clinically significant peripheral vascular disease within the past 6 months
- •Pulmonary embolism, deep-vein thrombosis, or other thromboembolic event within the past 6 months
- •Uncontrolled coronary artery disease, angina, congestive heart failure, or ventricular arrhythmia requiring acute medical management
- •Myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months
- •No evidence of bleeding diathesis or coagulopathy within the past 12 months
- •No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness or social situation that would limit study compliance
- •No known HIV positivity
- •See Disease Characteristics
- •Recovered from prior therapy
- •No prior VEGF-targeted antibody therapy (e.g., bevacizumab or aflibercept)
- •More than 4 weeks since prior systemic therapy or radiotherapy
- •More than 7 days since prior core biopsy
- •Up to 1 prior targeted biologic agent (e.g., small-molecule tyrosine kinase inhibitor or histone deacetylase inhibitor) allowed provided treatment was stopped ≥ 4 weeks prior to initiation of therapy on this study
- •Up to 1 prior cytotoxic chemotherapy (e.g., doxorubicin hydrochloride) allowed provided treatment was stopped ≥ 4 weeks prior to initiation of therapy on this study
- +15 more not shown
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Progression-free Survival to Determine the 6-month Progression-free-survival (PFS) Rate
Time Frame: 6 months
Progression-free survival to determine the 6-month progression-free-survival (PFS) rate
Radiographic Response Rate of Aflibercept in Patients With Recurrent and/or Metastatic Thyroid Cancer That Did Not Respond to Radioactive Iodine Therapy
Time Frame: After 8 weeks of study therapy
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions \& assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + P RMeasurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques (CT, MRI, x-ray) or as ≥ 10 mm with spiral CT scan. All tumor measurements must be recorded in millimeters (or decimal fractions of centimeters). All other lesions (or sites of disease), including small lesions (longest diameter \< 20 mm with conventional techniques or \< 10 mm using spiral CT scan), are considered non-measurable disease. Bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusions, lymphangitis cutis/pulmonis, inflammatory breast disease, abdominal masses (not followed by CT or MRI), \& cystic
Secondary Outcomes
- To Determine the Biologic Effect of IV VEGF Trap on FDG Avidity After Four Cycles (Approximately 8 Weeks) of Therapy Through Pre- and Post-treatment FDG-PET Scans in Patients With Recurrent and/or Metastatic D-TC-FCO.(8 weeks)
- Effect of Thyroglobulin Concentration on Progression-free Survival(6 months)
- The Safety and Toxicity Profile of IV VEGF Trap in Patients With Recurrent and/or Metastatic TC-FCO(From the beginning of treatment through 30 days until participant comes off study)