Pazopanib Hydrochloride in Treating Patients With Progressive Carcinoid Tumors
Condition: Foregut Neuroendocrine Tumor; Hindgut Neuroendocrine Tumor; Metastatic Carcinoid Tumor; Metastatic Digestive System Neuroendocrine Tumor G1; Midgut Neuroendocrine Tumor G1; Neuroendocrine Tumor G2; Recurrent Digestive System Neuroendocrine Tumor G1; Regional Digestive System Neuroendocrine Tumor G1
MeSH terms: Neoplasms; Neuroendocrine Tumors; Carcinoid Tumor; Intestinal Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms; Malignant Carcinoid Syndrome; Gastrointestinal Neoplasms
Intervention: Biospecimen Collection; Computed Tomography; Echocardiography; Laboratory Biomarker Analysis; Magnetic Resonance Imaging; Multigated Acquisition Scan; Pazopanib Hydrochloride; Placebo Administration; Quality-of-Life Assessment; X-Ray Imaging
Intervention description: Undergo blood sample collection; Undergo CT; Undergo ECHO; Correlative studies; Undergo MRI; Undergo MUGA; Given PO; Given PO; Ancillary studies; Undergo chest x-ray
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 171.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well pazopanib hydrochloride works in treating
      patients with carcinoid tumors that are growing, spreading, or getting worse. Pazopanib
      hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for
      cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Low- or intermediate-grade neuroendocrine carcinoma, including the following subtypes:
             carcinoid tumor, low- to intermediate-grade or well- to moderately-differentiated
             neuroendocrine carcinoma or tumor, atypical carcinoid tumor; documentation from a
             primary tumor or metastatic site is sufficient; patients with poorly differentiated
             neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid tumor,
             or goblet cell carcinoid tumor are not eligible

          -  Locally unresectable or metastatic carcinoid tumors

          -  Patients must have histologic documentation or clinical evidence of a carcinoid tumor
             of primary site (including foregut, midgut, hindgut or other non-pancreatic site);
             tumors of unknown primary site are eligible provided the treating physician does not
             suspect medullary thyroid cancer, pancreatic neuroendocrine tumor, paraganglioma, or
             pheochromocytoma; unknown primary tumors will be classified as small bowel tumors for
             the purpose of stratification; functional (associated with a clinical syndrome) or
             nonfunctional tumors are allowed; target lesions must have shown disease progression
             if therapy included peptide receptor radiotherapy (PRRT) and PRRT must be completed at
             least 8 weeks prior to registration

          -  Radiological evidence for progressive disease (measurable or non-measurable) within 12
             months prior to registration; patients who have received anti-tumor therapy during the
             past 12 months (including octreotide analogs) must have had radiological documentation
             of progression of disease while on or after receiving therapy

          -  No known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
             that increase the risk of pulmonary hemorrhage; patients with lesions infiltrating
             major pulmonary vessels (contiguous tumor and vessels) are excluded; however, the
             presence of a tumor that is touching, but not infiltrating (abutting) the vessels is
             acceptable (computed tomography [CT] with contrast is strongly recommended to evaluate
             such lesions); patients with large protruding endobronchial lesions in the main or
             lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi
             are allowed

          -  Patients must have measurable disease per RECIST 1.1 by computed 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); index lesions for the purpose of RECIST 1.1 measurements will not
             be selected from within the radiation therapy treatment field; however, if there is
             evidence of disease progression within the radiation treatment field, measurement of
             the progressing lesions will be documented

          -  No prior treatment with an inhibitor of vascular endothelial growth factor (VEGF) or
             vascular endothelial growth factor receptor (VEGFR)

          -  Prior treatment (somatostatin analogs excepted) must be completed at least 2 weeks
             prior to registration; in addition, prior treatment (somatostatin analogs excepted)
             must be completed at least 4 weeks prior to initiation of study drug;
             treatment-related toxicities must have improved to =< grade 1 prior to registration,
             with the exception of alopecia

          -  Concurrent use of somatostatin analogs (SSTa) is allowed, provided that the patient is
             on a stable dose for at least two months and progressive disease on somatostatin
             analog has been documented; progression on octreotide is required for patients with
             tumors arising in the midgut

          -  Prior treatment with 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 there is documented disease
             progression in a treated site; there is no limit on the prior number of procedures;
             prior liver-directed or other ablative treatment must be completed at least 8 weeks
             prior to registration; index lesions for the purpose of RECIST 1.1 measurements will
             not be selected from within the radiation therapy treatment field; however, if there
             is evidence of disease progression within the radiation treatment field, measurement
             of the progressing lesions will be documented

          -  Patients should have completed any major surgery >= 4 weeks prior to registration and
             must have completed any minor surgery >= 2 weeks prior to registration; patients must
             have fully recovered from the procedure

               -  The following are examples of procedures considered to be minor: port placement,
                  laparoscopy, thoracoscopy, bronchoscopy, mediastinoscopy, skin biopsies,
                  incisional biopsies, imaging-guided biopsy for diagnostic purposes, and dental
                  extraction procedures

               -  Insertion of a vascular access device, thoracentesis, paracentesis, and
                  endoscopic ultrasonographic procedures are not considered to be major or minor
                  surgeries

          -  No concurrent condition resulting in immune compromise, including chronic treatment
             with corticosteroids or other immunosuppressive agents

          -  No clinical evidence of central nervous system (CNS) metastases (including
             carcinomatous meningitis) at baseline, with the exception of those patients who have
             previously-treated CNS metastases (surgery +/- radiotherapy, radiosurgery, or gamma
             knife) and who meet both of the following criteria: a) are asymptomatic and b) had no
             requirement for steroids or enzyme-inducing anticonvulsants within 6 months prior to
             registration

          -  No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal
             abscess within 28 days prior to registration

          -  No clinically significant gastrointestinal abnormalities that may increase the risk
             for gastrointestinal bleeding within 28 days prior to registration including, but not
             limited to:

               -  Active peptic ulcer

               -  Known endoluminal metastatic lesion(s) with history of bleeding

               -  Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other
                  gastrointestinal conditions with increased risk of perforation

          -  No history of serious (i.e., requiring active medical therapy with medication or
             medical device under the supervision of a physician) non-healing wound, ulcer, trauma,
             or bone fracture within 28 days prior to study entry

          -  Patients with a history of hypertension must have blood pressure that is adequately
             controlled on antihypertensives; (< 140/90 mm Hg)

          -  No symptomatic congestive heart failure (New York Heart Association class II, III, or
             IV) within 6 months prior to registration

          -  No arterial thrombotic events within 6 months of registration, including transient
             ischemic attack (TIA), cerebrovascular accident (CVA), peripheral arterial thrombus,
             myocardial infarction (MI), or unstable angina or angina requiring surgical or medical
             intervention in 6 months prior to registration; patients with clinically significant
             peripheral artery disease (i.e., claudication on less than one block) are ineligible;
             patients who have experienced a deep venous thrombosis or pulmonary embolus within 6
             months prior to registration must be on stable therapeutic anticoagulation for at
             least 6 weeks prior to enrollment of this study

          -  Patients on therapeutic anticoagulation with low molecular weight heparins,
             fondaparinux, rivaroxaban or warfarin are eligible, provided that they are on a stable
             dose of anticoagulants; patients who are currently receiving antiplatelet therapy of
             prasugrel or clopidogrel or antiaggregation agents (e.g., eptifibatide, epoprostenol,
             dipyridamole) or low doses of acetylsalicylic acid (up to 100 mg daily) are also
             eligible

          -  No ongoing cardiac dysrhythmias, atrial fibrillation, or prolongation of corrected QT
             (QTc) interval to > 480 msec

          -  No evidence of active bleeding, bleeding diathesis, or hemoptysis (>= 1/2 teaspoon of
             red blood) within 8 weeks prior to registration

          -  No currently unstable angina and/or uncontrolled cardiac arrhythmias

          -  Patients with symptomatic peripheral vascular disease are ineligible

          -  Ejection fraction on echocardiogram (Echo) or multi gated acquisition scan (MUGA) >
             50%

          -  Chronic concomitant treatment with strong inhibitors of cytochrome P450, family 3,
             subfamily A, polypeptide 4 (CYP3A4) is not allowed on this trial; patients on strong
             CYP3A4 inhibitors must discontinue the drug 14 days prior to the start of study
             treatment

          -  Women must not be pregnant or nursing; women of child bearing potential must have a
             negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent
             units of human chorionic gonadotropin [HCG]) within 72 hours prior to registration;
             women of child-bearing potential include any female who has experienced menarche and
             who has not undergone surgical sterilization (hysterectomy, bilateral tubal ligation
             or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea >= 12
             consecutive months; or women on hormone replacement therapy [HRT] with documented
             serum follicle stimulating hormone [FSH] level > 35 mIU/mL)

          -  Age >= 18 years of age

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Granulocytes >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  International normalized ratio (INR) =< 1.2 X upper limit of normal (ULN); only
             required for patients receiving anticoagulant therapy; patients are eligible if their
             INR is stable and within the recommended range for the desired level of
             anticoagulation

          -  QTc =< 480 msecs

          -  Thyroid stimulating hormone (TSH) within normal limits (WNL); medications for thyroid
             dysfunction are allowed as long as TSH is normal at registration; in patients with
             abnormal TSH, if the free thyroxine (free T4) and free thyroxine index (FTI) are
             normal and patient is clinically euthyroid, patient is eligible

          -  Bilirubin =< 1.5 x ULN

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) &
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x
             ULN; concomitant elevations in bilirubin and AST/ALT above 1.0 X ULN are NOT
             permitted; also, if liver metastases are present, AST & ALT =< 5 x ULN is allowed

          -  Serum creatinine =< 1.5 x ULN

          -  Urine protein to creatinine ratio < 1, or, 24-hour urine protein < 1 g; if urine
             protein to creatinine (UPC) >= 1, then a 24-hour urine protein must be assessed;
             patients must have a 24-hour urine protein value < 1 g to be eligible; use of urine
             dipstick for renal function assessment is not acceptable