Pazopanib Hydrochloride in Treating Patients With Progressive Carcinoid Tumors

Not Recruiting

Trial ID: NCT01841736


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.

Official Title

Prospective Randomized Phase II Trial of Pazopanib (NSC #737754) Versus Placebo in Patients With Progressive Carcinoid Tumors

Stanford Investigator(s)

Shagufta Shaheen
Shagufta Shaheen

Clinical Assistant Professor, Medicine - Oncology

Heather Wakelee
Heather Wakelee

Professor of Medicine (Oncology)

George A. Fisher Jr.
George A. Fisher Jr.

Colleen Haas Chair in the School of Medicine


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

   - 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

   - 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

   - 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) >

   - 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

   - 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

   - 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


drug: Pazopanib Hydrochloride

other: Quality-of-Life Assessment

other: Laboratory Biomarker Analysis

other: Placebo Administration

procedure: Biospecimen Collection

procedure: Computed Tomography

procedure: Echocardiography

procedure: Magnetic Resonance Imaging

procedure: Multigated Acquisition Scan

procedure: X-Ray Imaging

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305

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