Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Carcinoma, Neuroendocrine

Carcinoma, Islet Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Adenocarcinoma

Neoplasms, Nerve Tissue

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Neuroendocrine Tumor

Neuroepithelioma

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Irinotecan

Leucovorin

Fluorouracil

Levoleucovorin

Folic Acid

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antidotes

Protective Agents

Vitamin B Complex

Trace Elements

Folinic Acid

Folate

Vitamin B9

Patients receive liposomal irinotecan IV over 90 minutes, leucovorin IV over 30 minutes, and fluorouracil IV over 46 hours on days 1 and 15. Courses repeat every 28 days for in the absence of disease progression or unacceptable toxicity.

Liposomal Irinotecan

Quality-of-Life Assessment

Renuka Iyer

This phase II trial studies how well liposomal irinotecan, leucovorin, and fluorouracil work in treating patients with high grade neuroendocrine cancer of gastrointestinal, unknown, or pancreatic origin that does not respond to treatment and has spread to other places in the body. Lliposomal irinotecan may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil and leucovorin, 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. Giving liposomal irinotecan, leucovorin and fluorouracil may work better in treating patients with neuroendocrine cancer.

PRIMARY OBJECTIVES:

I. To determine the objective response rate liposomal irinotecan (nanoliposomal irinotecan \[Nal-IRI\]) + fluorouracil (5FU) and leucovorin in patients with refractory advanced high grade neuroendocrine cancer of gastrointestinal (GI), unknown or pancreatic origin.

SECONDARY OBJECTIVES:

I. To determine overall survival, progression-free survival, time to treatment failure, safety, clinical response and, quality of life (QOL) changes resulting from the combination treatment of nanoliposomal irinotecan (Nal-IRI) + fluorouracil (5FU) and leucovorin.

EXPLORATORY OBJECTIVES:

I. Genetic profiling for mutations will be conducted on all pre-study tumor samples and compared to changes in immune response.

OUTLINE:

Patients receive liposomal irinotecan intravenously (IV) over 90 minutes, leucovorin IV over 30 minutes, and fluorouracil IV over 46 hours on days 1 and 15. Courses repeat every 28 days for in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days, then every 2 months thereafter.

Liposomal Irinotecan, Fluorouracil and Leucovorin in Treating Patients With Refractory Advanced High Grade Neuroendocrine Cancer of Gastrointestinal, Unknown, or Pancreatic Origin

Phase 2 Single-Arm Study of Nanoliposomal Irinotecan With Fluorouracil and Leucovorin in Refractory Advanced High Grade Neuroendocrine Cancer of GI, Unknown or Pancreatic Origin

Will be summarized using frequencies and relative frequencies; with the ORR (= CR+PR / N) estimated using an 80% confidence interval obtained using Jeffrey's prior method. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions.

Will be summarized using standard Kaplan-Meier methods; where estimates of the median time will be obtained with 95% confidence intervals.

Will be summarized using standard Kaplan-Meier methods; where estimates of the median time will be obtained with 95% confidence intervals. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Will be summarized using standard Kaplan-Meier methods; where estimates of the median time will be obtained with 90% confidence intervals.

The objective response rate (ORR) is as described in the primary analysis. Here it is reported in the subset of patients that received prior platinum etoposide therapy.

Defined as either achievement of pronounced and sustained (\>=4 weeks contiguous) improvement in pain intensity, analgesic consumption, or performance status, or a combination of these, without any worsening in any of the other factors, or stability in pain intensity, analgesic consumption, and performance status with pronounced and sustained (\>= 4 weeks contiguous) weight gain. Will be treated as binary data and summarized using frequencies and relative frequencies. The clinical benefit response rate will be estimated using a 90% confidence interval obtained by Jeffrey?s prior method.

Will be treated as quantitative data and summarized by time-point using the mean and standard deviation. The QOL scores at each follow-up time may be compared with base-line levels using the paired t-test or sign test. The overall QoL rating ranges from 0 (poor) to 10 (good).

Toxicities and adverse events will be summarized by attribution and grade using frequencies and relative frequencies. High grade (3+) toxicity and adverse event rates may be estimated using 90% confidence intervals obtained by Jeffrey's prior method. Data Safety Monitoring Board (DSMB) monitoring will also occur periodically to ensure safety of study subjects.

Ipsen

Roswell Park Cancer Institute

Patients receive liposomal irinotecan IV over 90 minutes, leucovorin IV over 30 minutes, and fluorouracil IV over 46 hours on days 1 and 15. Courses repeat every 28 days for in the absence of disease progression or unacceptable toxicity.

Fluorouracil: Given IV

Leucovorin: Given IV

Liposomal Irinotecan: Given IV

Quality-of-Life Assessment: Correlative studies

Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil)

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

The number of prior chemotherapy regimens for the current cancer diagnsosis.

Number of Prior Chemotherapy Regimens

Kris Attwood

2 patients were not evaluable for response.

Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Overall Survival

Progression-free Survival Assessed by RECIST 1.1

Time-to Treatment Failure

Only 4 patients received prior platinum etoposide.

Proportion of Patients Achieving an Objective Response Based on Prior Response to Platinum Etoposide

The appropriate data to identify patient clinical benefit status (as defined above) was not adequately obtained (no available data) and analysis can not be conducted for this outcome measure.

Clinical Benefit Response

Comparing the pre-treatment and end of treatment QoL scores.

Pre Treatment QoL

End of Treatment QoL

There are 11 patients that have QoL data at baseline (pre-treatment). There are only 8 patients with end of treatment QoL assessment.

Quality of Life (QOL) as Assessed by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30)

Incidence of Grade 3+ Treatment Related Adverse Events (TRAE)

Overall Study

Adenoma

Adenoma, Islet Cell

Pancreatic Neuroendocrine Tumor

Capecitabine

Temozolomide

Lutetium Lu 177 dotatate

Antineoplastic Agents, Alkylating

Alkylating Agents

Radiopharmaceuticals

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.

Lutetium Lu 177 Dotatate

Questionnaire Administration

Timothy J. Hobday, MD

Site Public Contact

Timothy J. Hobday

Andrew E. Hendifar

Pamela L. Kunz

Ana D. De Jesus Acosta

Thomas J. Saphner

Bryan A. Faller

Al B. Benson

Chih-Yi Liao

Hussein Assi

Daniel Almquist

Laura L. Tenner

Joni A. Tilford

Kathryn C. Hourdequin

Bahar Laderian

Edward M. Wolin

Rahul Seth

Timothy J. b, MD

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.

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.

Comparing Capecitabine and Temozolomide in Combination to Lutetium Lu 177 Dotatate in Patients With Advanced Pancreatic Neuroendocrine Tumors

Phase II Randomized, Prospective Trial of Lutetium Lu 177 Dotatate PRRT Versus Capecitabine and Temozolomide in Well-Differentiated Pancreatic Neuroendocrine Tumors

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.

Kaplan-Meier methodology will be used to estimate the PFS rate at 2 years.

Kaplan-Meier methodology will be used to estimate the PFS rate at 3 years.

Kaplan-Meier methodology will be used to estimate the median time to progression (TTP).

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).

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.

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.

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.

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.

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.

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Liposomal Irinotecan, Fluorouracil and Leucovorin in Treating Patients With Refractory Advanced High Grade Neuroendocrine Cancer of Gastrointestinal, Unknown, or Pancreatic Origin	NCT03736720	Locally Advance... Locally Advance... Metastatic Dige... Metastatic Panc... Refractory Dige... Refractory Panc... Unresectable Di... Unresectable Pa...	Fluorouracil Leucovorin Liposomal Irino... Quality-of-Life...	18 Years -	Roswell Park Cancer Institute
Comparing Capecitabine and Temozolomide in Combination to Lutetium Lu 177 Dotatate in Patients With Advanced Pancreatic Neuroendocrine Tumors	NCT05247905	Metastatic Panc... Unresectable Pa...	Lutetium Lu 177... Capecitabine Temozolomide Quality-of-Life... Questionnaire A...	18 Years -	Alliance for Clinical Trials in Oncology

Spots Global Cancer Trial Database for unresectable pancreatic neuroendocrine carcinoma