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Clinical Trial 19732

Cancer Type:
Interventions:

Study Type: Treatment
Phase of Study: Phase III
Investigators:

  • Jonathan Strosberg

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

Randomized, Double-Blinded Phase III Study of Cabozantinib Versus Placebo in Patients with Advanced Neuroendocrine Tumors after Progression on Everolimus (Cabinet)

Summary

This trial studies cabozantinib S-malate to see how well it works compared with placebo in treating patients with neuroendocrine tumors previously treated with everolimus that have spread to nearby tissues or lymph nodes, have spread to other places in the body, or cannot be removed by surgery. Cabozantinib S-malate is a chemotherapy drug known as a tyrosine kinase inhibitor, and it targets specific tyrosine kinase receptors, that when blocked, may slow tumor growth.

Objective

Primary Objectives 2.1.1 To determine whether cabozantinib can significantly improve progression-free survival (PFS) compared to placebo in patients with advanced pancreatic NET whose disease has progressed after treatment with everolimus. 2.1.2 To determine whether cabozantinib can significantly improve progression-free survival (PFS) compared to placebo in patients with advanced carcinoid tumors whose disease has progressed after treatment with everolimus. Secondary Objectives 2.2.1 To determine whether cabozantinib can significantly improve overall survival (OS) compared to placebo in patients with advanced pancreatic NET whose disease has progressed after treatment with everolimus. 2.2.2 To determine whether cabozantinib can significantly improve overall survival (OS) compared to placebo in patients with advanced carcinoid tumors whose disease has progressed after treatment with everolimus. 2.2.3 To evaluate safety and tolerability of cabozantinib versus placebo in patients with advanced pancreatic NET using CTCAE and PRO-CTCAE. 2.2.4 To evaluate safety and tolerability of cabozantinib versus placebo in patients with advanced carcinoid tumors using CTCAE and PRO-CTCAE. 2.2.5 To evaluate the overall radiographic response rate of cabozantinib versus placebo in patients with advanced pancreatic NET whose disease has progressed after treatment with everolimus. 2.2.6 To evaluate the overall radiographic response rate of cabozantinib versus placebo in patients with advanced carcinoid tumors whose disease has progressed after treatment with everolimus. 2.3 Other Objective Results of the primary analysis will be examined for consistency, while taking into account the stratification factors and/or covariates of baseline QOL and fatigue.

Inclusion Criteria

>>> Inclusion Criteria:

  • 18 years of age and older
  • Documentation of Disease: Histologic Documentation: Well- or moderately-differentiated neuroendocrine tumors of pancreatic and non-pancreatic (i.e. carcinoid) origin by local pathology. Stage: Locally advanced/unresectable or metastatic disease. Tumor Site: Histological documentation of neuroendocrine tumor of pancreatic, gastrointestinal (GI), lung, or unknown primary site. Radiologic Evaluation: Target lesions must have shown evidence of disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria in the 12 months prior to registration; the radiologic images, imaging reports, and clinic notes indicating growth of existing lesions, development of new lesions, or treatment changes must be submitted.
  • Measurable Disease: Patients must have measurable disease per RECIST 1.1 by computer tomography (CT) scan or magnetic resonance imaging (MRI). Lesions must be accurately measured in at least one dimension (longest diameter to be recorded) as >= 1 cm with CT or MRI (or >= 1.5 cm for lymph nodes); non-measurable disease includes disease smaller than these dimensions or lesions considered truly non-measurable including: leptomeningeal disease, ascites, pleural or pericardial effusion, lymphangitic involvement of skin or lung.
  • Prior Treatment: Patient must have failed at least one prior systemic therapy that included everolimus; disease progression or treatment intolerance leading to discontinuation is considered treatment failure. Prior treatment (except somatostatin analogs) with biologic therapy, immunotherapy, chemotherapy, investigational agent for malignancy, and/or radiation must be completed at least 28 days prior to registration. Prior treatment with somatostatin analogs is allowed, and continuation of treatment with somatostatin analogs while on cabozantinib/placebo is allowed provided that the patient has been on a stable dose for at least two months. Prior systemic treatment with radionuclide therapy must be completed at least 6 weeks prior to registration. Prior treatment with hepatic artery embolization (including bland embolization, chemoembolization, and selective internal radiation therapy) or ablative therapies is allowed if measurable disease remains outside of the treated area or if there is documented disease progression in a treated site; prior liver-directed or other ablative treatment must be completed at least 28 days prior to registration. Prior treatment with cabozantinib is not allowed.
  • Patients should have resolution of any toxic effects of prior therapy (except alopecia and fatigue) to National Cancer Institute (NCI) CTCAE, version 5.0, grade 1 or less.
  • Patients must have completed any major surgery at least 12 weeks prior to registration and any minor surgery (including uncomplicated tooth extractions) at least 28 days prior to registration; complete wound healing from major surgery must have occurred at least 28 days prior to registration, and complete wound healing from minor surgery must have occurred at least 10 days prior to registration.
  • Adequate organ function

  • Exclusion Criteria

    >>> Exclusion Criteria

  • Not pregnant and not nursing.
  • Class III or IV congestive heart failure (CHF) within 6 months of registration
  • Clinically significant cardiac arrhythmia within 6 months of registration
  • Unstable angina or MI within 6 months of registration
  • Thromboembolic events within 6 months of registration (including [incl.] stroke, transient ischemic attack [TIA], deep vein thrombosis [DVT], & pulmonary embolism [PE])
  • Known history of congenital long QT syndrome
  • Uncontrolled hypertension within 14 days of registration.
  • Clinically significant GI bleeding within 6 months of registration
  • Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding within 6 months of registration.
  • GI perforation within 6 months of registration.
  • Known tumor invading the GI tract within 28 days of registration.
  • Radiologic or clinical evidence of pancreatitis.
  • Known cavitary lung lesions.
  • Known endobronchial lesions involving the main or lobar bronchi and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage; (CT with contrast is recommended to evaluate such lesions)
  • Hhemoptysis greater than 1/2 teaspoon (2.5 mL) or any other signs of pulmonary hemorrhage within the 3 months prior to registration.
  • Known tumor invading or encasing any major blood vessels
  • History of non-healing wounds or ulcers within 28 days of registration
  • History of fracture within 28 days of registration.
  • Brain metastases or cranial epidural disease unless adequately treated, stable, and off steroid support for at least 4 weeks prior to registration.
  • Known medical condition causing an inability to swallow oral formulations of agents.
  • History of allergic reaction attributed to compounds of similar chemical or biological composition to cabozantinib/placebo.
  • "Currently active" second malignancy other than non-melanoma skin cancers or cervical carcinoma in situ.
  • Concomitant Medications: Other planned concurrent investigational agents or other tumor directed therapies (chemotherapy, radiation) are not allowed while on this study. Concurrent use of somatostatin analogs while on cabozantinib/placebo is allowed provided that the patient has been on a stable dose for at least two months. Full dose oral anticoagulation/antiplatelet therapy is not permitted; low dose aspirin =< 81 mg/day is allowed; anticoagulation with therapeutic doses of low molecular weight heparin (LMWH) is allowed in patients who are on a stable dose of LMWH for at least 6 weeks prior to registration; treatment with warfarin is not allowed; anticoagulation in patients with brain metastases is not permitted.Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed; patients must discontinue the drug at least 14 days prior to registration on the study. Chronic concomitant treatment with strong CYP3A4 inducers is not allowed; patients must discontinue the drug at least 14 days prior to the start of study treatment.