Neoplasms

All Conditions

Blood and Lymph Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Neuroendocrine Tumors

Thymoma

Thymus Neoplasms

Adenoma

Adenoma, Islet Cell

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Neoplasms, Glandular and Epithelial

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Thoracic Neoplasms

Lymphatic Diseases

Neuroendocrine Tumor

Pancreatic Neuroendocrine Tumor

Non Functioning Pancreatic Endocrine Tumor

Functioning Pancreatic Endocrine Tumor

Neuroepithelioma

Pancreatic Cancer

Patients receive ribociclib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Pharmacological Study

Ribociclib

Nageshwara V Dasari

This phase II trial studies how well ribociclib works in treating patients with neuroendocrine tumors of the foregut, which includes the thymus, lung, stomach, and pancreas, that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced tumors). Ribociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To estimate the Response Evaluation Criteria in Solid Tumors (RECIST) (per version 1.1) objective response rate of LEE011 (ribociclib) among patients with advanced foregut neuroendocrine tumors (NETs).

SECONDARY OBJECTIVES:

I. To evaluate the progression free survival duration of LEE011 among patients with advanced foregut NETs.

II. To evaluate the safety and tolerability of LEE011 in patients with advanced foregut NETs.

III. To determine clinic benefit rate at 6 months (defined as complete response plus partial response plus stable disease) with LEE011 among patients with advanced foregut NETs.

EXPLORATORY OBJECTIVES:

I. To determine baseline molecular markers (mutations, deletions, and amplifications in multiple endocrine neoplasia \[MEN\]1, p27, p16 and cyclin D1 \[CCND1\]) in archival tumor that may predict clinical benefit at 6 months from LEE011.

II. To determine potential mechanisms/markers of resistance. III. To determine early chromogranin and neuron specific enolase responses in patients with elevated levels at baseline.

IV. To determine the pharmacodynamic changes including proliferation-related Ki-67 antigen (Ki-67) and phosphorylated retinoblastoma (pRb) upon treatment with LEE011 in patients with advanced foregut NETs.

OUTLINE:

Patients receive ribociclib orally (PO) once daily (QD) on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Ribociclib in Treating Patients With Advanced Neuroendocrine Tumors of Foregut Origin

A Phase II Study of LEE011 (Ribociclib) in Patients With Advanced Neuroendocrine Tumors of Foregut Origin

Decrease in pRB as Measured by Immunohistochemistry (IHC) in Biopsies From Baseline and From cycle 2 day 1. H-scores were calculated as the sum of the products of the percentage of positive staining areas and the staining intensity (0, 1, 2 or 3), and ranged from 0 to 300. A score of 0 represents the absence of expression, and an H-score of 300 represents maximum expression.

Ki-67 was calculated as a percentage cells staining positive by Immunohistochemistry (IHC).

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Number of Participants that did not have progressive disease at 6 months.

PFS is the length of time during and after the treatment that a participant lives with the disease but it does not get worse.The Kaplan-Meier (KM) method will be used to estimate the PFS.

National Cancer Institute (NCI)

Novartis

M.D. Anderson Cancer Center

LEE011 will be taken orally, once a day for 21 consecutive days followed by a 7 day planned break. LEE011 will be dosed on a flat dosing scale of 600 mg/day, irrespective of size and weight.

Study Participants

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Arvind Dasari,MBBS

Number of Participants With Response Rate Per Response Evaluation Criteria in Solid Tumors Version 1.1

Spots Global Cancer Trial Database for gastric neuroendocrine tumor