Neoplasms

All Conditions

Rare Diseases

Neuroendocrine Tumors

Carcinoid Tumor

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Gastro-enteropancreatic Neuroendocrine Tumor

Neuroepithelioma

Pharmaceutical Solutions

All Drugs and Chemicals

Antineoplastic Agents

Fluorodeoxyglucose F18

Olaparib

Somatostatin

Lutetium Lu 177 dotatate

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Lu-177-DOTATATE and escalating doses of olaparib to determine the maximum-tolerated dose (MTD)

Lu-177-DOTATATE will be given by IV every 8 (+/-2) weeks for a total of 4 administrations

Lu-177-DOTATATE

Olaparib is given as a pill taken orally and is to be taken twice a day, starting from 2 days before the first administration of Lu-177-DOTATATE until 4 weeks after the last administration

Ga68-DOTATATE PET/CT scan will be done at baseline, at week 32, then every 24 weeks in followup period.

Ga dotatate scanning

F18-FDG PET/CT scan will be done at baseline, at week 32, then every 24 weeks in followup period.

FDG-PET scanning

Concomitant administration of an IV infusion of an amino acid (AA) solution will also be done for renal protection. The AA infusion will begin at least 30-60 minutes prior to injection of Lu-177-DOTATATE and will continue during and after the Lutathera infusion until the entire prescribed amount is infused.

Amino Acid infusion

Joy Zou, R.N.

Frank I Lin, M.D.

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

Background:

A neuroendocrine tumor is a rare type of tumor. It comes from body cells called neuroendocrine cells. Sometimes, these tumors develop in the gastrointestinal tract and pancreas. Researchers want to find out if a combination of drugs can shrink these tumors.

Objective:

To learn if people with certain neuroendocrine tumors can take a combination of 2 drugs, Lutathera and Olaparib, without having severe side effects, and if this treatment makes the tumors shrink.

Eligibility:

Adults 18 and older who have a neuroendocrine tumor in the pancreas or intestine that cannot be cured by surgery and has somatostatin receptors on the cells.

Design:

Participants will be screened under protocol 01-C-0129. They may have a tumor biopsy.

Eligible participants will get Lutathera through an intravenous (IV) infusion every 8 weeks for 4 cycles. One cycle is 8 weeks. Each cycle includes a follow-up visit at week 4. For the IV, a small plastic tube is put into an arm vein.

Participants will also take Olaparib by mouth twice a day for 4 weeks of each cycle. They will use a medicine diary to track the doses.

During the study, participants will have physical exams. They will have blood and urine tests. They will fill out questionnaires about their general well-being and function. Their heart function will be tested. They will have scans of their chest, abdomen, and pelvis. One type of scan will use an IV infusion of a radioactive tracer.

Participants will have a follow-up visit about 4 weeks after treatment ends. Then they will have follow-up visits every 12 weeks for 3 years. Then they will have yearly phone calls.

Background:

* Neuroendocrine tumors (NETs) of the gastrointestinal tract and pancreas are a rare and heterogeneous, but clinically important, group of neoplasms with unique tumor biology, natural history, and clinical management issues.
* While the treatment of localized NETs is surgical resection, a variety of therapeutic options are available for patients with advanced NETs. These include medical control of excess hormone levels and associated symptoms, cytoreductive surgery for patients with advanced disease, radioembolization, chemoembolization, systemic chemotherapy, interferon, longacting somatostatin analogs, receptor-targeted radionuclide therapy, and or liver transplantation.
* Somatostatin receptors (SSTR) have been shown to be overexpressed in a number of human tumors, including neuroblastoma, prostate cancer, pheochromocytomas, paragangliomas, and NETs, among many others.
* Lu-177-DOTATATE (Lutathera) is a SSTR-agonist agent which emits ionizing radiation that causes DNA damage to its target cells through both direct and indirect mechanisms. In addition, ionizing radiation has also been shown to induce cell death through what is known as the bystander effect, a phenomenon where cellular signaling from irradiated cells towards non-irradiated cells induces cellular damage and eventually death in nearby surrounding cells.
* Olaparib is a PARP inhibitor indicated as monotherapy in patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. Olaparib has an established safety

profile and it is under investigation in several different cancers.

- The rationale behind using combination therapies in cancer stems from the potential of synergistic mechanisms of action of the involved agents. Olaparib is a PARP-inhibitor which blocks the repair of single-stranded DNA breaks and is especially effective when combined with other agents which induces DNA damage.

Objectives:

* Phase I:

  * Characterize the safety profile and tolerability of the olaparib + Lu-177-DOTATATE combination.
  * Determine the maximum tolerated dose (MTD) dose of the combination using the 3+3 dose escalation design.
* Phase II:

  * Measure the Best Overall Response Rate (BOR) by RECIST 1.1 at the MTD dose at completion of 4 cycles of treatment.

Eligibility:

* Clinical diagnosis of GEP-NET disease, histologically confirmed to be consistent with neuroendocrine tumor.
* Inoperable disease (metastatic, non-candidate for surgery with curative intent, locally advanced into vessels or other critical structures, etc.).
* Age \>=18 years.
* Must have presence of SSTR+ disease as documented by positive Ga-68-DOTATATE PET scan within 12 weeks prior to anticipated treatment.
* ECOG Performance Status \<= 1.

Design:

* Open-label, single-arm, single-center, phase I/II study evaluating the safety and efficacy of the Lu-177-DOTATATE + olaparib combination in patients with inoperable GEP-NET.
* For phase I, a standard 3+3 design will be used to determine MTD. It is estimated that approximately 15 to 24 patients will be required. Phase II will involve the use of a Simon optimal two-stage design to determine sample size and interim stopping rule.
* Assuming a combination of inevaluable patients or loss-to-follow-up of 10%, up to 24 patients will be accrued to phase I and 15 patients to phase II including the 6 phase I patients at MTD, with a total accrual ceiling of 42 patients to allow for a small number of inevaluable patients.

Lu-177-DOTATATE (Lutathera) in Combination With Olaparib in Inoperable Gastroenteropancreatico Neuroendocrine Tumors (GEP-NET)

Phase I/II Study of Lu-177-DOTATATE (Lutathera) in Combination With Olaparib in Inoperable Gastroenteropancreatico Neuroendocrine Tumors (GEP-NET)

.All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.

Depending on what the speed of dose escalation and the final MTD dose, it is estimated that for 4 dose levels with up to 6 patients at each level, approximately 12 to 24 patients will be required for the phase I portion of the study. Standard 3+3 design will be used.

Proportion of patients who have a partial or complete response to therapy.

Kaplan-Meier curves of PFS and OS will be constructed. Median PFS and OS will be reported with 95% confidence intervals.

Preliminary information on the BOR will be presented as a percentage with 95% confidence intervals. Only evaluate patients will be included. Kaplan-Meier curves of PFS will be constructed. Median PFS will be reported with 95% confidence intervals.

National Cancer Institute (NCI)

Digestive System Diseases

Gland and Hormone Related Diseases

Stomach Neoplasms

Colorectal Neoplasms

Pancreatic Neoplasms

Intestinal Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Pancreatic Diseases

Endocrine System Diseases

Stomach Diseases

Stomach Cancer

Pancreatic Cancer

Adult patients with well defined grade 1 and grade 2 GEP-NETs. Serial serum samples from all patients will be analyzed using the BRAHMS CgA II KRYPTOR Assay.

The BRAHMS CgA II KRYPTOR kit is an automated immunofluorescent assay for the quantitative determination of the concentration of CgA in human serum.

The assay is to be used as an aid in monitoring disease progression during the course of disease and treatment in patients with GEP-NETs (grade 1 and grade 2).

Serial testing for patient BRAHMS CgA II KRYPTOR assay values should be used in conjunction with other clinical methods for monitoring GEP-NETs (grade 1 and grade 2).

BRAHMS CgA II KRYPTOR

Daniel M Halperin, MD

Gastroentero-pancreatic neuroendocrine tumors (GEP-NETs) are a heterogenous group of neoplasms that arise from enterochromaffin cells of the gastrointestinal (GI) tract and pancreas. They account for 50-70% of all incident NETs. Due to the lack of symptoms in the early stage of disease and the frequency of nonspecific GI symptoms, GEP-NETs are difficult to diagnose.

Identification of effective biomarkers (such as Chromogranin A) to improve GEP-NET diagnosis, as well as to assess treatment efficacy, relapse and prognosis, is important for improving outcomes for patients with GEP-NETs.

The purpose of this study is to validate the performance of Brahms (BRAHMS) Chromogranin A II Kryptor (KRYPTOR) assay to monitor the course of disease in patients with well-defined GEP-NETs.

A general characteristic for neuroendocrine tumors (NET) is expression of chromogranin A (CgA), which is released from neuroendocrine cells, occasionally together with cell specific hormones such as gastrin, insulin, somatostatin, and serotonin in functional tumors. Human CgA is an acidic 439 amino acid protein with a sequence containing several mono- and dibasic cleavage sites, and correspondingly, numerous fragments of CgA have been identified in tissue and plasma. CgA is critical to the formation of secretory granules that characterize NETs, and is therefore a useful marker for NETs.

Plasma concentrations of CgA and/or CgA fragments are elevated in most NETs. Moreover, since plasma CgA concentrations seem to be closely related to tumor burden in humans, plasma CgA concentration is an important prognostic factor. As such, high plasma concentrations of CgA as well as a dramatic increase in plasma CgA within a short time period, is associated with a poorer prognosis. Plasma CgA has also been suggested to be useful in the follow-up of patients with NETs.

Taken together, these observations support the notion that CgA is a promising biomarker candidate for monitoring treatment effectiveness and disease progression or regression.

Participation in this clinical study requires no additional visits to the oncologist, radiology or the laboratory. All information needed for the study will be obtained during typical visits as recommended by the oncologist. Clinical assessment of patients with GEP-NETs (according to NCCN guidelines) is based on physical exam, imaging (CT or MRI scans) and laboratory parameters. The course of disease is followed by RECIST 1.1 categorization including the evaluation of tumor burden by imaging.

Chromogranin A as Blood Marker in Cancer Patients

Chromogranin A as Surveillance Biomarker in Patients With cARcinoids (The CASPAR Study)

Progression vs. non-progression in patients with well-defined GEP-NETs assessed by RECIST 1.1 criteria

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Lu-177-DOTATATE (Lutathera) in Combination With Olaparib in Inoperable Gastroenteropancreatico Neuroendocrine Tumors (GEP-NET)	NCT04086485	Gastroenteropan... Neuroendocrine ... Neuroendocrine ...	Lu-177-DOTATATE Olaparib Ga dotatate sca... FDG-PET scannin... Amino Acid infu...	18 Years -	National Institutes of Health Clinical Center (CC)
Chromogranin A as Blood Marker in Cancer Patients	NCT03817866	Gastric Neoplas... Pancreatic Neop... Small Intestina... Colorectal Neop...	BRAHMS CgA II K...	18 Years - 85 Years	Brahms AG

Spots Global Cancer Trial Database for carcinoids

Every month we try and update this database with for carcinoids cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for carcinoids

Every month we try and update this database with for carcinoids cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for carcinoids cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.