A Study of LEE011 With Everolimus in Patients With Advanced Neuroendocrine Tumors

NCT03070301 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 16-1535
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to test any good and bad effects of the combination of LEE011 with everolimus on the participant and the cancer.

Conditions

Neuroendocrine Tumors

Keywords

LEE011; Everolimus; 16-1535

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  using RECIST v1.1

  12 months

Study Arms (1)

LEE011 and everolimus

EXPERIMENTAL

Subjects will receive LEE011 200 mg daily, in combination with everolimus 5 mg daily; in the setting of toxicity, everolimus dosing will be changed to 2.5 mg daily or 2.5 mg every other day. Subjects will continue treatment until meeting one of the criteria for removal from study.

Drug: LEE011; Drug: everolimus

Interventions

LEE011 DRUG

LEE011 200 mg daily

LEE011 and everolimus

everolimus DRUG

everolimus 5 mg daily or 2.5mg daily

LEE011 and everolimus

Eligibility Criteria

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

You may qualify if:

• Patient has signed the Informed Consent prior to any screening procedures being performed and is able to comply with the protocol requirements.
• Adults ≥ 18 years old
• Histologic or cytologic diagnosis of a WDNET, Ki67 ≤ 30%, unresectable, of foregut origin (thymic, bronchopulmonary, gastric, duodenal, and pancreatic) confirmed by the enrolling institution
• \*Note: If patients have a functional NET, they are permitted to continue on a somatostatin analog for hormonal symptom control
• MSK patient has tissue available from a previous biopsy for the evaluation of potential predictive biomarkers. If tissue is not available for MSK patient, a new tumor specimen will need to be obtained prior to the start of study treatment If archived tissue is available, participating site patient will provide for the evaluation of potential predictive biomarkers. If tissue is not available for participating site patient, a new tumor specimen is optional prior to the start of study treatment.
• Documented radiological evidence for disease progression (measurable or nonmeasurable) ≤12 months prior to enrollment
• Disease that is currently not amenable to surgical resection with curative intent as determined by the treating investigator
• Measurable disease as defined by RECIST v1.1
• ECOG performance status 0 or 1 or KPS performance status 100 to 70
• Patient has adequate bone marrow and organ function as defined by the following laboratory values at screening:
• Absolute neutrophil count ≥1.5 x 10\^9/L
• Platelets ≥ 100 x 10\^9/L
• Hemoglobin ≥ 9.0 g/dL
• INR ≤ 1.5
• Serum creatinine \<1.5mg/dL or creatinine clearance ≥ 50 mL/min

You may not qualify if:

• Patient has a known hypersensitivity to any of the excipients of LEE011 or everolimus
• Previous treatment with a CDK 4/6 inhibitor or an mTOR inhibitor
• Has had prior chemotherapy, targeted small molecule therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent
• \*Note: Subjects with \< Grade 2 neuropathy or chemotherapy-induced alopecia are an exception to this criterion and may qualify for the study
• Patient has a concurrent malignancy or malignancy within 3 years prior to starting study drug, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer
• Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:
• At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment
• Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases
• Patient 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)
• Patient has a known history of HIV infection (testing not mandatory)
• Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator"s judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol (e.g. chronic pancreatitis, active untreated or uncontrolled fungal, bacterial or viral infections, etc.).
• Uncontrolled diabetes mellitus as defined by HbA1c \>8% despite adequate therapy. Patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary
• Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following:
• History of myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to study entry
• Documented cardiomyopathy

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Novartis: collaborator
• Dana-Farber Cancer Institute: collaborator
• M.D. Anderson Cancer Center: collaborator

Study Sites (5)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Md Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Raj N, Zheng Y, Hauser H, Chou J, Rafailov J, Bou-Ayache J, Sawan P, Chaft J, Chan J, Perez K, Rudin C, Tang L, Reidy-Lagunes D. Ribociclib and everolimus in well-differentiated foregut neuroendocrine tumors. Endocr Relat Cancer. 2021 Apr;28(4):237-246. doi: 10.1530/ERC-20-0446.

  PMID: 33640871 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

ribociclib; Everolimus

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. Diane Reidy-Lagunes, MD
• Organization: Memorial Sloan Kettering Cancer Center

reidyd@mskcc.org

646-888-4185

Study Officials

• Diane Reidy-Lagunes, MD, MS

  Memorial Sloan Kettering 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

Model Details: This will be a multicenter, non-randomized, open-label phase II clinical trial.

Study Record Dates

• First Submitted: February 28, 2017
• First Posted: March 3, 2017
• Study Start: February 27, 2017
• Primary Completion: January 31, 2024
• Study Completion: January 31, 2024
• Last Updated: October 10, 2024
• Results First Posted: October 10, 2024

Record last verified: 2024-10

Locations

US (5)