Ribociclib in Treating Patients With Advanced Neuroendocrine Tumors of Foregut Origin

NCT02420691 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: 2014-0371NCI-2015-01017P30CA016672
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Digestive System Neuroendocrine Neoplasm; Duodenal Neuroendocrine Tumor G1; Functional Pancreatic Neuroendocrine Tumor; Gastric Neuroendocrine Tumor; Intermediate Grade Lung Neuroendocrine Neoplasm; Low Grade Lung Neuroendocrine Neoplasm; Nonfunctional Pancreatic Neuroendocrine Tumor; Thymus Neoplasm

Outcome Measures

Primary Outcomes (1)

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

  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.

  3 years 10 months

Secondary Outcomes (2)

• Number of Participants With Clinical Benefit Rate

  At 6 months

• Progression Free Survival (PFS)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to 24 months

Other Outcomes (2)

• Change in pRB With Treatment

  Baseline (Pre-Treatment) and Cycle 2 Day 1, each Cycle is 28 days

• Change in Ki-67 With Treatment

  Baseline (Pre-Treatment) and Cycle 2 Day 1, each Cycle is 28 days

Study Arms (1)

Treatment (ribociclib)

EXPERIMENTAL

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

Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Ribociclib

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ribociclib)

Pharmacological Study OTHER

Correlative studies

Treatment (ribociclib)

Ribociclib DRUG

Given PO

Also known as: Kisqali, LEE-011, LEE011

Treatment (ribociclib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed low or intermediate grade, unresectable well differentiated foregut neuroendocrine tumors (thymic, bronchopulmonary, gastric, duodenal and pancreatic); patients with multiple neuroendocrine tumors associated with MEN1 syndrome will be eligible
• Patients must have radiographically measurable disease
• Pancreatic neuroendocrine patients must have had progression after prior therapy; patients with other foregut neuroendocrine tumors must have had progressive disease over the last 12 months, irrespective of prior therapy; patients with both functional (who may continue somatostatin analogues as required for control of related symptoms) and non-functional tumors are eligible; in patients who have previously received therapy, the number of prior lines of therapy should not be more than 2 lines of systemic therapy not including somatostatin analogues
• Written informed consent must be obtained prior to any screening procedures
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
• A sufficient interval must have elapsed between the last dose of prior anti-cancer therapy (including cytotoxic and biological therapies and major surgery) and enrollment, to allow the effects of prior therapy to have abated: a) cytotoxic or targeted chemotherapy: greater than or equal to the duration of the cycle of the most recent treatment regimen (a minimum of 3 weeks for all regimens, except 6 weeks for nitrosoureas and mitomycin-C); b) biologic therapy (e.g., antibodies): greater than or equal to 4 weeks
• Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10\^9/L
• Hemoglobin (Hgb) greater than or equal to 9 g/dL
• Platelets greater than or equal to 100 x 10\^9/L
• Serum total bilirubin less than or equal to 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) less than or equal to 2.5 x ULN, except in patients with tumor involvement of the liver who must have AST and ALT less than or equal to 5 x ULN
• Serum creatinine less than or equal to 1.5 x ULN or 24-hour clearance greater than or equal to 50 mL/min
• Serum potassium (corrected for serum albumin) must be within clinically relevant limits (e.g., a patient can be enrolled if a lab value may be outside the normal laboratory range but the abnormality is not clinically relevant or can be repleted)
• Sodium (corrected for serum albumin) must be within clinically relevant limits (e.g., a patient can be enrolled if a lab value may be outside the normal laboratory range but the abnormality is not clinically relevant or can be repleted)
• Magnesium (corrected for serum albumin) must be within clinically relevant limits (e.g., a patient can be enrolled if a lab value may be outside the normal laboratory range but the abnormality is not clinically relevant or can be repleted)

You may not qualify if:

• Patient has a known hypersensitivity to LEE011 or any of its excipients
• Patients with known or suspected brain metastases; however, if radiation therapy and/or surgery has been completed and serial evaluation by computed tomography (CT) (with contrast enhancement) or magnetic resonance imaging (MRI) over a minimum of 3 months demonstrates the disease to be stable and if the patient remains asymptomatic, then the patient may be enrolled; such patients must have no need for treatment with steroids or anti-epileptic medications
• Patients with concurrent malignancies or malignancies within 3 years prior to starting study drug (with the exception of tumors common to a single genetic cancer syndrome, i.e. MEN1, MEN2, von Hippel-Lindau \[vHL\], tuberous sclerosis complex \[TSC\] etc., or adequately treated, basal cell skin cancer, squamous cell carcinoma, non-melanoma skin cancer or curatively resected cervical cancer)
• Patient is not able to swallow oral medication and/or has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• Known diagnosis of human immunodeficiency virus (HIV) or hepatitis C (testing is not mandatory)
• Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicate patient participation in the clinical study (e.g. chronic pancreatitis, chronic active hepatitis, etc.)
• Patient who has received radiotherapy within less than or equal to 4 weeks or limited field radiation for palliation within less than or equal to 2 weeks prior to starting study drug, and who has not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia) and/or in whom greater than or equal to 30% of the bone marrow was irradiated
• Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered as major surgery)
• Impaired cardiac function or clinically significant cardiac diseases, including any of the following: a) history of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis less than 12 months prior to screening b) history of documented congestive heart failure (New York Heart Association functional classification III-IV) c) documented cardiomyopathy d) patient has a left ventricular ejection fraction (LVEF) less than 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening e) history of ventricular, supraventricular, nodal arrhythmias, or any other cardiac arrhythmias, long QT syndrome or conduction abnormality within 12 months prior to starting study drug f) congenital long QT syndrome or a family history of corrected QT interval (QTc) prolongation g) on screening, inability to determine the corrected QT for Fridericia (QTcF) interval on the electrocardiogram (ECG) (i.e.: unreadable or not interpretable) or QTcF \> 450 msec (using Fridericia's correction); all as determined by screening ECG (mean of triplicate ECGs)
• Systolic blood pressure greater than 160 mmHg or less than 90 mmHg at screening
• Patients who are currently receiving treatment with agents that are known to cause QTc prolongation or inducing Torsade de Pointes in humans and are unable to discontinue or switch to an alternate medication
• Patients who are currently receiving treatment (within 5 days prior to starting study drug) with agents that are known strong inducers or inhibitors of cytochrome P450, family 3, subfamily A polypeptide 4 (CYP3A4)/cytochrome P450, family 3, subfamily A polypeptide 5 (5), or that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5
• Patients with concurrent severe and/or uncontrolled concurrent medical conditions that could compromise participation in the study (e.g., uncontrolled diabetes mellitus defined by a glucose greater than 1.5 ULN in spite of adequate medical treatment, clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection)
• Patient has a history of non-compliance to medical regimen or inability to grant consent
• Pregnant or lactating women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (greater than 5 mIU/mL)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• Novartis: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Non functioning pancreatic endocrine tumor; Thymus Neoplasms

Interventions

ribociclib

Condition Hierarchy (Ancestors)

Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lymphatic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Arvind Dasari,MBBS
• Organization: UT MD Anderson Cancer Center

adasari@mdanderson.org

713-792-2828

Study Officials

• Nageshwara V Dasari

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2015
• First Posted: April 20, 2015
• Study Start: August 25, 2015
• Primary Completion: June 5, 2019
• Study Completion: June 5, 2019
• Last Updated: October 30, 2020
• Results First Posted: October 30, 2020

Record last verified: 2020-10

Locations

US (1)