Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05247905
Other study ID # A022001
Secondary ID NCI-2021-14404U1
Status Recruiting
Phase Phase 2
First received
Last updated
Start date March 16, 2022
Est. completion date October 2033

Study information

Verified date May 2024
Source Alliance for Clinical Trials in Oncology
Contact Timothy J. Hobday, MD
Phone 507-284-8413
Email hobday.timothy@mayo.edu
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This phase II trial compares capecitabine and temozolomide to lutetium Lu 177 dotatate for the treatment of pancreatic neuroendocrine tumors that have spread to other parts of the body (advanced) or are not able to be removed by surgery (unresectable). Chemotherapy drugs, such as capecitabine and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radioactive drugs, such as lutetium Lu 177 dotatate, may carry radiation directly to tumor cells and may reduce harm to normal cells. The purpose of this study is to find out whether capecitabine and temozolomide or lutetium Lu 177 dotatate may kill more tumor cells in patients with advanced pancreatic neuroendocrine tumors.


Description:

This phase II trial compares capecitabine and temozolomide to lutetium Lu 177 dotatate for the treatment of pancreatic neuroendocrine tumors that have spread to other parts of the body (advanced) or are not able to be removed by surgery (unresectable). Chemotherapy drugs, such as capecitabine and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radioactive drugs, such as lutetium Lu 177 dotatate, may carry radiation directly to tumor cells and may reduce harm to normal cells. The purpose of this study is to find out whether capecitabine and temozolomide or lutetium Lu 177 dotatate may kill more tumor cells in patients with advanced pancreatic neuroendocrine tumors. The primary and secondary objectives of the study: PRIMARY OBJECTIVE: I. To determine the differences in median progression-free survival (PFS) for lutetium Lu 177 dotatate peptide receptor radionuclide therapy (PRRT) when compared to capecitabine and temozolomide (CAPTEM) in patients with locally advanced or metastatic progressive, well-differentiated pancreatic neuroendocrine tumors (pNETs). SECONDARY OBJECTIVES: I. To evaluate and compare the overall survival (OS) of patients receiving lutetium Lu 177 dotatate versus (vs.) CAPTEM. II. To evaluate and compare time to response, time to maximum response, and overall response rates (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 between both arms. III. To evaluate and compare duration of response and time to progression among both arms. IV. To evaluate and compare treatment related toxicities between the arms. V. To compare global health status/quality of life as measured with the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 from baseline through 18 months between patients with pNET treated with lutetium Lu 177 dotatate PRRT versus capecitabine and temozolomide. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive lutetium Lu 177 dotatate intravenously (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. ARM II: Patients receive capecitabine orally (PO) twice daily (BID) days 1-14 and temozolomide PO once daily (QD) on days 10-14. Treatment repeats every 4 weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity.


Recruitment information / eligibility

Status Recruiting
Enrollment 198
Est. completion date October 2033
Est. primary completion date March 31, 2028
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Lutetium Lu 177 Dotatate
Given IV
Capecitabine
Given PO
Temozolomide
Given PO
Other:
Quality-of-Life Assessment
Ancillary studies
Questionnaire Administration
Ancillary studies

Locations

Country Name City State
United States Hickman Cancer Center Adrian Michigan
United States Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore Maryland
United States Advocate Good Shepherd Hospital Barrington Illinois
United States Nebraska Medicine-Bellevue Bellevue Nebraska
United States Tower Cancer Research Foundation Beverly Hills California
United States Illinois CancerCare-Bloomington Bloomington Illinois
United States Prisma Health Cancer Institute - Spartanburg Boiling Springs South Carolina
United States Boston Medical Center Boston Massachusetts
United States Montefiore Medical Center - Moses Campus Bronx New York
United States Montefiore Medical Center-Einstein Campus Bronx New York
United States Montefiore Medical Center-Weiler Hospital Bronx New York
United States Aurora Cancer Care-Southern Lakes VLCC Burlington Wisconsin
United States Illinois CancerCare-Canton Canton Illinois
United States Saint Francis Medical Center Cape Girardeau Missouri
United States Southeast Cancer Center Cape Girardeau Missouri
United States Memorial Hospital of Carbondale Carbondale Illinois
United States SIH Cancer Institute Carterville Illinois
United States Illinois CancerCare-Carthage Carthage Illinois
United States Centralia Oncology Clinic Centralia Illinois
United States Advocate Illinois Masonic Medical Center Chicago Illinois
United States Northwestern University Chicago Illinois
United States University of Chicago Comprehensive Cancer Center Chicago Illinois
United States University of Illinois Chicago Illinois
United States Marshfield Clinic-Chippewa Center Chippewa Falls Wisconsin
United States Baptist Memorial Hospital and Cancer Center-Collierville Collierville Tennessee
United States AMG Crystal Lake - Oncology Crystal Lake Illinois
United States Aurora Saint Luke's South Shore Cudahy Wisconsin
United States Cancer Care Specialists of Illinois - Decatur Decatur Illinois
United States Decatur Memorial Hospital Decatur Illinois
United States Northwestern Medicine Cancer Center Kishwaukee DeKalb Illinois
United States Smilow Cancer Hospital-Derby Care Center Derby Connecticut
United States Illinois CancerCare-Dixon Dixon Illinois
United States Advocate Good Samaritan Hospital Downers Grove Illinois
United States Epic Care-Dublin Dublin California
United States Prisma Health Cancer Institute - Easley Easley South Carolina
United States Marshfield Medical Center-EC Cancer Center Eau Claire Wisconsin
United States Crossroads Cancer Center Effingham Illinois
United States Advocate Sherman Hospital Elgin Illinois
United States Bay Area Breast Surgeons Inc Emeryville California
United States Epic Care Partners in Cancer Care Emeryville California
United States Saint Vincent Hospital Erie Pennsylvania
United States Illinois CancerCare-Eureka Eureka Illinois
United States Smilow Cancer Hospital Care Center-Fairfield Fairfield Connecticut
United States Parkland Health Center - Farmington Farmington Missouri
United States Illinois CancerCare-Galesburg Galesburg Illinois
United States Western Illinois Cancer Treatment Center Galesburg Illinois
United States Northwestern Medicine Cancer Center Delnor Geneva Illinois
United States Aurora Health Care Germantown Health Center Germantown Wisconsin
United States Smilow Cancer Hospital Care Center at Glastonbury Glastonbury Connecticut
United States Aurora Cancer Care-Grafton Grafton Wisconsin
United States Aurora BayCare Medical Center Green Bay Wisconsin
United States Aurora Health Center - Greenfield Greenfield Wisconsin
United States Prisma Health Cancer Institute - Butternut Greenville South Carolina
United States Prisma Health Cancer Institute - Eastside Greenville South Carolina
United States Prisma Health Cancer Institute - Faris Greenville South Carolina
United States Prisma Health Greenville Memorial Hospital Greenville South Carolina
United States Smilow Cancer Hospital Care Center at Greenwich Greenwich Connecticut
United States Prisma Health Cancer Institute - Greer Greer South Carolina
United States Smilow Cancer Hospital Care Center - Guilford Guilford Connecticut
United States Smilow Cancer Hospital Care Center at Saint Francis Hartford Connecticut
United States Advocate South Suburban Hospital Hazel Crest Illinois
United States Mayo Clinic in Florida Jacksonville Florida
United States MU Health Care Goldschmidt Cancer Center Jefferson City Missouri
United States Jefferson Hospital Jefferson Hills Pennsylvania
United States Aurora Cancer Care-Kenosha South Kenosha Wisconsin
United States Illinois CancerCare-Kewanee Clinic Kewanee Illinois
United States Marshfield Medical Center - Ladysmith Ladysmith Wisconsin
United States Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center Lebanon New Hampshire
United States AMG Libertyville - Oncology Libertyville Illinois
United States Condell Memorial Hospital Libertyville Illinois
United States Cancer Partners of Nebraska Lincoln Nebraska
United States Cancer Partners of Nebraska - Pine Lake Lincoln Nebraska
United States Cedars Sinai Medical Center Los Angeles California
United States Illinois CancerCare-Macomb Macomb Illinois
United States Aurora Bay Area Medical Group-Marinette Marinette Wisconsin
United States Marshfield Medical Center-Marshfield Marshfield Wisconsin
United States Contra Costa Regional Medical Center Martinez California
United States Toledo Clinic Cancer Centers-Maumee Maumee Ohio
United States Baptist Memorial Hospital and Cancer Center-Memphis Memphis Tennessee
United States Aurora Cancer Care-Milwaukee Milwaukee Wisconsin
United States Aurora Saint Luke's Medical Center Milwaukee Wisconsin
United States Aurora Sinai Medical Center Milwaukee Wisconsin
United States Medical College of Wisconsin Milwaukee Wisconsin
United States Marshfield Clinic-Minocqua Center Minocqua Wisconsin
United States Toledo Clinic Cancer Centers-Monroe Monroe Michigan
United States Forbes Hospital Monroeville Pennsylvania
United States Yale University New Haven Connecticut
United States UC Comprehensive Cancer Center at Silver Cross New Lenox Illinois
United States Mount Sinai Hospital New York New York
United States Yale-New Haven Hospital North Haven Medical Center North Haven Connecticut
United States Cancer Care Center of O'Fallon O'Fallon Illinois
United States Advocate Christ Medical Center Oak Lawn Illinois
United States Advocate Outpatient Center - Oak Lawn Oak Lawn Illinois
United States Bay Area Tumor Institute Oakland California
United States Nebraska Medicine-Village Pointe Omaha Nebraska
United States University of Nebraska Medical Center Omaha Nebraska
United States Smilow Cancer Hospital-Orange Care Center Orange Connecticut
United States Northwestern Medicine Orland Park Orland Park Illinois
United States University of Chicago Medicine-Orland Park Orland Park Illinois
United States Vince Lombardi Cancer Clinic - Oshkosh Oshkosh Wisconsin
United States Illinois CancerCare-Ottawa Clinic Ottawa Illinois
United States Advocate Lutheran General Hospital Park Ridge Illinois
United States Illinois CancerCare-Pekin Pekin Illinois
United States Illinois CancerCare-Peoria Peoria Illinois
United States Methodist Medical Center of Illinois Peoria Illinois
United States Illinois CancerCare-Peru Peru Illinois
United States Valley Radiation Oncology Peru Illinois
United States Mayo Clinic Hospital in Arizona Phoenix Arizona
United States Allegheny General Hospital Pittsburgh Pennsylvania
United States West Penn Hospital Pittsburgh Pennsylvania
United States Illinois CancerCare-Princeton Princeton Illinois
United States Aurora Cancer Care-Racine Racine Wisconsin
United States Marshfield Medical Center-Rice Lake Rice Lake Wisconsin
United States Mayo Clinic in Rochester Rochester Minnesota
United States Missouri Baptist Medical Center Saint Louis Missouri
United States Sainte Genevieve County Memorial Hospital Sainte Genevieve Missouri
United States Huntsman Cancer Institute/University of Utah Salt Lake City Utah
United States Prisma Health Cancer Institute - Seneca Seneca South Carolina
United States Vince Lombardi Cancer Clinic-Sheboygan Sheboygan Wisconsin
United States Sanford Cancer Center Oncology Clinic Sioux Falls South Dakota
United States Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota
United States Baptist Memorial Hospital and Cancer Center-Desoto Southhaven Mississippi
United States Memorial Medical Center Springfield Illinois
United States Southern Illinois University School of Medicine Springfield Illinois
United States Springfield Clinic Springfield Illinois
United States Smilow Cancer Hospital Care Center at Long Ridge Stamford Connecticut
United States Marshfield Medical Center-River Region at Stevens Point Stevens Point Wisconsin
United States Missouri Baptist Sullivan Hospital Sullivan Missouri
United States Aurora Medical Center in Summit Summit Wisconsin
United States BJC Outpatient Center at Sunset Hills Sunset Hills Missouri
United States State University of New York Upstate Medical University Syracuse New York
United States Toledo Clinic Cancer Centers-Toledo Toledo Ohio
United States Torrance Memorial Physician Network - Cancer Care Torrance California
United States Smilow Cancer Hospital-Torrington Care Center Torrington Connecticut
United States Smilow Cancer Hospital Care Center-Trumbull Trumbull Connecticut
United States Vince Lombardi Cancer Clinic-Two Rivers Two Rivers Wisconsin
United States Epic Care Cyberknife Center Walnut Creek California
United States Northwestern Medicine Cancer Center Warrenville Warrenville Illinois
United States Illinois CancerCare - Washington Washington Illinois
United States Sibley Memorial Hospital Washington District of Columbia
United States Smilow Cancer Hospital-Waterbury Care Center Waterbury Connecticut
United States Smilow Cancer Hospital Care Center - Waterford Waterford Connecticut
United States Marshfield Clinic-Wausau Center Wausau Wisconsin
United States Aurora Cancer Care-Milwaukee West Wauwatosa Wisconsin
United States Aurora West Allis Medical Center West Allis Wisconsin
United States Smilow Cancer Hospital Care Center - Westerly Westerly Rhode Island
United States Marshfield Medical Center - Weston Weston Wisconsin
United States Wexford Health and Wellness Pavilion Wexford Pennsylvania
United States Marshfield Clinic - Wisconsin Rapids Center Wisconsin Rapids Wisconsin
United States Sanford Cancer Center Worthington Worthington Minnesota

Sponsors (2)

Lead Sponsor Collaborator
Alliance for Clinical Trials in Oncology National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Progression free survival (PFS) Progression free survival (PFS) will be compared between the two treatment arms using Kaplan-Meier methods. The hazard ratio (HR) and median PFSwill be estimated along with corresponding 95% confidence intervals. Up to 8 years from randomization
Secondary Progression Free Survival (PFS) at 2 years Kaplan-Meier methodology will be used to estimate the PFS rate at 2 years. At 2 years from randomization
Secondary Progression Free Survival (PFS) at 3 years Kaplan-Meier methodology will be used to estimate the PFS rate at 3 years. At 3 years from randomization
Secondary Time to progression (TTP) Kaplan-Meier methodology will be used to estimate the median time to progression (TTP). Up to 8 years from randomization
Secondary Overall survival (OS) Kaplan-Meier methodology will be used to estimate the median overall survival (OS). OS is defined as randomization to the time of death due to any cause (or censored at the time of last contact for surviving patients and those lost to follow-up). Up to 8 years from study registration
Secondary Objective response rate (ORR) The response rate (percentage) is the percent of patients whose best response was Complete Response (CR) or Partial Response (PR) as defined by RECIST 1.1 criteria. Percentage of successes will be estimated by 100 times the number of successes divided by the total number of evaluable patients. Response rates (including complete and partial response) will be tested using Fisher's exact test. Up to 8 years from randomization
Secondary Time-to response Kaplan-Meier methodology will be used to estimate the median time-to-response. Time-to-response will be defined as the time from randomization to the first tumor response, for those patients having achieved an objective response. Up to 8 years from randomization
Secondary Duration of response Kaplan-Meier methodology will be used to estimate the median duration of response. Duration of response will be defined as the time from first assessment with documented response (PR or CR) to the time of progression and/or death. Patients who are still responding as of their last evaluation will be censored at the time point. If we observed documented deaths without progression, we will further evaluate this endpoint with death without progression treated as a competing risk. Up to 8 years from randomization
Secondary Incidence of adverse events Patients will be evaluated for adverse events using the National Cancer Institute Common Toxicity Criteria for Adverse Events version 5.0. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported. Up to 8 years from randomization
Secondary Change in Overall Health Question (Q29) from the EORTC QLQ-C30 questionnaire To evaluate between-arm differences in patient-reported global health status from baseline through 18 months, the area under the curve will be calculated as a summary statistic for each arm based on estimates from a mixed model for patient-reported global health status/quality of life as assessed by the EORTC QLQ-C30 at baseline, 3, 6, 12, and 18 months. At baseline up to 18 months
Secondary Change in Overall Quality of Life Question (Q30) from the EORTC QLQ-C30 questionnaire To evaluate between-arm differences in patient-reported quality of life from baseline through 18 months, the area under the curve will be calculated as a summary statistic for each arm based on estimates from a mixed model for patient-reported global health status/quality of life as assessed by the EORTC QLQ-C30 at baseline, 3, 6, 12, and 18 months. At baseline up to 18 months
See also
  Status Clinical Trial Phase
Active, not recruiting NCT03375320 - Testing Cabozantinib in Patients With Advanced Pancreatic Neuroendocrine and Carcinoid Tumors Phase 3
Recruiting NCT03879694 - Survivin Long Peptide Vaccine in Treating Patients With Metastatic Neuroendocrine Tumors Phase 1
Recruiting NCT05687123 - Testing the Addition of Sunitinib Malate to Lutetium Lu 177 Dotatate (Lutathera) in Pancreatic Neuroendocrine Tumors Phase 1