Comparing Capecitabine and Temozolomide in Combination to Lutetium Lu 177 Dotatate in Patients With Advanced Pancreatic Neuroendocrine Tumors
Metastatic Pancreatic Neuroendocrine Tumor, Unresectable Pancreatic Neuroendocrine Carcinoma
About this trial
This is an interventional treatment trial for Metastatic Pancreatic Neuroendocrine Tumor
Eligibility Criteria
Inclusion Criteria:
- Histologic or pathologic documentation: well-differentiated pancreatic neuroendocrine tumor (G1, G2, or well-differentiated G3) confirmed by local histology and/or pathology
- Functional or nonfunctional tumors are allowed
- Stage: locally unresectable or metastatic disease
- Tumor Site: neuroendocrine tumor of pancreatic primary site
- Radiologic evaluation: tumor must have shown somatostatin receptor (SSTR) positivity on 68Ga-DOTATATE PET or other SSTR-PET scan in the 12 months prior to registration; however, documentation of SSTR positivity in the 6 months prior to registration is preferred. SSTR positivity is defined as uptake greater than background liver in all measurable lesions
Patients are eligible if they meet one of the following criteria:
- Previously untreated patients with grade 2 or 3 disease AND with symptoms of either disease bulk causing pain, anorexia, early satiety, large effusions/ascites, abdominal pain, abdominal fullness due to hepatomegaly, dyspnea) OR incompletely controlled symptoms of hormone excess despite somatostatin analogue (SSA) and supportive care (including but not limited to: diarrhea, hypercalcemia, hypoglycemia, hyperglycemia, flushing, Cushing's syndrome). Patient may have been started on SSA for up to 2 months for attempted symptom control without disease progression prior to registration
- Patients previously treated with SSA only and with disease progression by RECIST in prior 12 months
- Patients previously treated with SSA and one or more prior systemic therapy must have received prior anti-vascular endothelial growth factor (VEGF) pathway therapy inhibitor OR have contraindication to anti-VEGF therapy (including but not limited to: uncontrolled hypertension [systolic blood pressure [SBP] > 150 and/or diastolic blood pressure [DBP] > 90 despite medical management], stage IIB or greater heart disease, angina pectoris, prior arterial [ATE] and venous thromboembolic [VTE] events in the past 6 months, gastrointestinal [GI] bleed in the last 6 months) and disease progression by RECIST in prior 12 months
- Patients previously treated with more than 2 lines of therapy, not including anti VEGF therapy, but with NET related symptoms as outlined in first bullet (pain, anorexia, early satiety, large effusions/ascites, abdominal pain, abdominal fullness due to hepatomegaly, anorexia, early satiety, dyspnea) OR incompletely controlled symptoms of hormone excess despite somatostatin analogue (SSA) and supportive care (including but not limited to: diarrhea, hypercalcemia, hypoglycemia, hyperglycemia, flushing, Cushing's syndrome).
- Any patient with disease progression by RECIST criteria in < 4 months
Patients must have measurable disease per RECIST v1.1 by computer tomography (CT) scan or magnetic imaging (MRI). Any lesions which have undergone percutaneous therapies or radiotherapy after starting protocol therapy should not be considered measurable unless the lesion has clearly progressed since the procedure.
* Lesions must be accurately measured in at least one dimension (longest diameter to be recorded) as >= 1 cm with CT or MRI (or shortest diameter >= 1.5 cm for lymph nodes). Non-measurable disease includes disease smaller than these dimensions or lesions considered truly non- measurable including: leptomeningeal disease, bone metastases, ascites, pleural or pericardial effusion, lymphangitic involvement of skin or lung.
- Prior treatment with tyrosine kinase inhibitors (TKIs) such as mammalian target of rapamycin (mTOR) inhibitors (e.g. everolimus, temsirolimus, etc.) or VEGF pathway inhibitors (e.g. sunitinib, pazopanib, cabozantinib, bevacizumab, etc.) are allowed
- Prior treatment with hepatic intra-arterial embolic therapies is allowed if there is recovery from all toxicities, measurable lesions do not include embolized liver unless there has been clear subsequent progression, all measurable lesions are somatostatin receptor avid, and treatment completed at least 2 months prior to registration
- Prior treatment with cryoablation or thermal/radiofrequency ablation of metastases is allowed if there is recovery from all toxicities, measurable lesions do not include treated metastases, and treatment completed at least 2 months prior to registration
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Absolute neutrophil count (ANC) >= 1,500/mm^3
- Platelet count >= 100,000/mm^3
- Hemoglobin >= 9.0 g/dL
- Creatinine =< 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance >= 30 mL/min (calculated by the Cockcroft-Gault equation)
- Total bilirubin =< 1.5 x ULN (in patients with liver metastases or known Gilbert's syndrome, total bilirubin must be =< 3.0 x ULN)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x ULN
- Albumin >= 3.0 g/dL
Concurrent somatostatin analog use while on protocol therapy is allowed provided that the patient:
- Has a functional tumor (evidence of peptide hormones and/or bioactive substances associated with a clinical hormone syndrome such as carcinoid syndrome or Cushing's syndrome)
- Has been on a stable dose of somatostatin analog therapy for at least three months
- Has previously demonstrated radiographic disease progression while on somatostatin analog therapy. For subjects receiving lutetium Lu 177 dotatate, there should be a minimum of 14 days between long-acting somatostatin analogue and lutetium Lu 177 dotatate dosing. Short-acting somatostatin analogs should not be administered within 24 hours of lutetium Lu 177 dotatate dosing. Following lutetium Lu 177 dotatate dosing, long-acting somatostatin analogs may be administered between 4 and 24 hours after each dose
Exclusion Criteria:
- Patients with poorly differentiated neuroendocrine carcinoma (large cell histology or small cell histology) are not eligible
- No prior temozolomide, dacarbazine, capecitabine, 5-FU, or any PRRT for treatment of the pNET
Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects
* Therefore, for women of childbearing potential only, a negative pregnancy test done =< 14 days prior to registration is required
- No known brain metastases unless adequately treated, demonstrated to be stable, and off all treatment (including steroids) for at least 2 months prior to registration
- No uncontrolled congestive heart failure (New York Heart Association [NYHA] II, III, IV).
- No significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may pose a risk to patient safety
- No "currently active" second malignancy other than non-melanoma skin cancers or cervical carcinoma in situ. Patients are not considered to have a "currently active" malignancy if they have completed therapy or are on adjuvant hormonal therapy and are free of disease for >= 3 years
- No known medical condition causing an inability to swallow and no known impairment of gastrointestinal function that may significantly alter the absorption of an oral agent
Sites / Locations
- Tower Cancer Research FoundationRecruiting
- Epic Care-DublinRecruiting
- Bay Area Breast Surgeons IncRecruiting
- Epic Care Partners in Cancer CareRecruiting
- Cedars Sinai Medical CenterRecruiting
- Contra Costa Regional Medical CenterRecruiting
- Bay Area Tumor InstituteRecruiting
- Torrance Memorial Physician Network - Cancer CareRecruiting
- Epic Care Cyberknife CenterRecruiting
- Smilow Cancer Hospital-Derby Care CenterRecruiting
- Smilow Cancer Hospital Care Center-FairfieldRecruiting
- Smilow Cancer Hospital Care Center at GlastonburyRecruiting
- Smilow Cancer Hospital Care Center at GreenwichRecruiting
- Smilow Cancer Hospital Care Center - GuilfordRecruiting
- Smilow Cancer Hospital Care Center at Saint FrancisRecruiting
- Yale UniversityRecruiting
- Yale-New Haven Hospital North Haven Medical CenterRecruiting
- Smilow Cancer Hospital-Orange Care CenterRecruiting
- Smilow Cancer Hospital Care Center at Long RidgeRecruiting
- Smilow Cancer Hospital-Torrington Care CenterRecruiting
- Smilow Cancer Hospital Care Center-TrumbullRecruiting
- Smilow Cancer Hospital-Waterbury Care CenterRecruiting
- Smilow Cancer Hospital Care Center - WaterfordRecruiting
- Sibley Memorial HospitalRecruiting
- Illinois CancerCare-BloomingtonRecruiting
- Illinois CancerCare-CantonRecruiting
- Memorial Hospital of CarbondaleRecruiting
- SIH Cancer InstituteRecruiting
- Illinois CancerCare-CarthageRecruiting
- Centralia Oncology ClinicRecruiting
- Northwestern UniversityRecruiting
- University of IllinoisRecruiting
- University of Chicago Comprehensive Cancer CenterRecruiting
- Cancer Care Specialists of Illinois - DecaturRecruiting
- Decatur Memorial HospitalRecruiting
- Northwestern Medicine Cancer Center KishwaukeeRecruiting
- Illinois CancerCare-DixonRecruiting
- Crossroads Cancer CenterRecruiting
- Illinois CancerCare-EurekaRecruiting
- Illinois CancerCare-GalesburgRecruiting
- Western Illinois Cancer Treatment CenterRecruiting
- Northwestern Medicine Cancer Center DelnorRecruiting
- Illinois CancerCare-Kewanee ClinicRecruiting
- Illinois CancerCare-MacombRecruiting
- UC Comprehensive Cancer Center at Silver CrossRecruiting
- Cancer Care Center of O'FallonRecruiting
- University of Chicago Medicine-Orland ParkRecruiting
- Illinois CancerCare-Ottawa ClinicRecruiting
- Illinois CancerCare-PekinRecruiting
- Illinois CancerCare-PeoriaRecruiting
- Methodist Medical Center of IllinoisRecruiting
- Illinois CancerCare-PeruRecruiting
- Valley Radiation OncologyRecruiting
- Illinois CancerCare-PrincetonRecruiting
- Southern Illinois University School of MedicineRecruiting
- Springfield ClinicRecruiting
- Memorial Medical CenterRecruiting
- Northwestern Medicine Cancer Center WarrenvilleRecruiting
- Illinois CancerCare - WashingtonRecruiting
- Johns Hopkins University/Sidney Kimmel Cancer CenterRecruiting
- Boston Medical CenterRecruiting
- Hickman Cancer CenterRecruiting
- Toledo Clinic Cancer Centers-MonroeRecruiting
- Mayo Clinic in RochesterRecruiting
- Sanford Cancer Center WorthingtonRecruiting
- Baptist Memorial Hospital and Cancer Center-DesotoRecruiting
- Saint Francis Medical CenterRecruiting
- Southeast Cancer CenterRecruiting
- Parkland Health Center - FarmingtonRecruiting
- Capital Region Southwest CampusRecruiting
- Missouri Baptist Medical CenterRecruiting
- Sainte Genevieve County Memorial HospitalRecruiting
- Missouri Baptist Sullivan HospitalRecruiting
- Missouri Baptist Outpatient Center-Sunset HillsRecruiting
- Nebraska Medicine-BellevueRecruiting
- Cancer Partners of Nebraska - Pine LakeRecruiting
- Southeast Nebraska Cancer Center - 68th Street PlaceRecruiting
- Nebraska Medicine-Village PointeRecruiting
- University of Nebraska Medical CenterRecruiting
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer CenterRecruiting
- Montefiore Medical Center-Einstein CampusRecruiting
- Montefiore Medical Center-Weiler HospitalRecruiting
- Montefiore Medical Center - Moses CampusRecruiting
- Mount Sinai HospitalRecruiting
- State University of New York Upstate Medical UniversityRecruiting
- Toledo Clinic Cancer Centers-MaumeeRecruiting
- Toledo Clinic Cancer Centers-ToledoRecruiting
- Saint Vincent HospitalRecruiting
- Jefferson HospitalRecruiting
- Forbes HospitalRecruiting
- Allegheny General HospitalRecruiting
- West Penn HospitalRecruiting
- Wexford Health and Wellness PavilionRecruiting
- Smilow Cancer Hospital Care Center - WesterlyRecruiting
- Prisma Health Cancer Institute - SpartanburgRecruiting
- Prisma Health Cancer Institute - EasleyRecruiting
- Prisma Health Cancer Institute - ButternutRecruiting
- Prisma Health Cancer Institute - FarisRecruiting
- Prisma Health Greenville Memorial HospitalRecruiting
- Prisma Health Cancer Institute - EastsideRecruiting
- Prisma Health Cancer Institute - GreerRecruiting
- Prisma Health Cancer Institute - SenecaRecruiting
- Sanford Cancer Center Oncology ClinicRecruiting
- Sanford USD Medical Center - Sioux FallsRecruiting
- Baptist Memorial Hospital and Cancer Center-ColliervilleRecruiting
- Baptist Memorial Hospital and Cancer Center-MemphisRecruiting
- Huntsman Cancer Institute/University of UtahRecruiting
- Marshfield Clinic-Chippewa CenterRecruiting
- Marshfield Medical Center-EC Cancer CenterRecruiting
- Marshfield Clinic - Ladysmith CenterRecruiting
- Marshfield Medical Center-MarshfieldRecruiting
- Medical College of WisconsinRecruiting
- Marshfield Clinic-Minocqua CenterRecruiting
- Marshfield Medical Center-Rice LakeRecruiting
- Marshfield Medical Center-River Region at Stevens PointRecruiting
- Marshfield Clinic-Wausau CenterRecruiting
- Marshfield Medical Center - WestonRecruiting
- Marshfield Clinic - Wisconsin Rapids CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Arm I (lutetium Lu 177 dotatate)
Arm II (capecitabin, temozolomide)
Patients receive lutetium Lu 177 dotatate IV over 30 minutes on day 1. Treatment repeats every 8 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
Patients receive capecitabine PO BID days 1-14 and temozolomide PO QD on days 10-14. Treatment repeats every 4 weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity.