Study of Everolimus (RAD001) in Combination With Lenalidomide

NCT01218555 | Completed Phase 1 Results DMC

• 2 other identifiers: IRB00031088WCI1717-09
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to study the combination of two anticancer drugs, everolimus (RAD001) and lenalidomide in patients whose cancer is no longer responding to standard treatment or patients who are unable to tolerate the standard treatment for their cancer.

Conditions

Solid Organ Malignancies; Adenoidcystic Carcinoma; Neuroendocrine Tumors

Keywords

kidney cancer; adenoidcystic cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose Limiting Toxicities (DLT) at Each Dose Level

  A standard 3 + 3 design was employed to study escalating doses of daily, orally administered lenalidomide and everolimus. Dose escalation to the next cohort required 0 of 3 or ≤1 of 6 patients with dose-limiting toxicity (DLT). Five dose cohorts were planned starting at dose level one with lenalidomide 10 mg and everolimus 5mg in a 28-day cycle up to maximum doses of 25 and 10 mg, respectively.

  Within the first 28 days for DLT and throughout the duration of the study for safety.

Study Arms (1)

Lenalidomide combination with everolimus

EXPERIMENTAL

Non-randomized study of escalating doses of daily, orally administered lenalidomide in combination with standard doses of everolimus, an orally available mammalian target of rapamycin (mTOR) inhibitor.

Drug: Lenalidomide; Drug: Everolimus

Interventions

Lenalidomide DRUG

Lenalidomide (10mg, 15mg, 20mg or 25mg) once daily by mouth, every day of each 28-day cycle.

Also known as: Revlimid

Lenalidomide combination with everolimus

Everolimus DRUG

5mg or 10mg of everolimus administered once daily by mouth on a once daily continuous dosing schedule for 28 days.

Also known as: RAD001, Afinitor

Lenalidomide combination with everolimus

Eligibility Criteria

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

You may not qualify if:

• Ability to understand and willingness to voluntarily sign an informed consent form.
• Histologic or cytologic confirmation of a solid malignancy.
• Age ≥ 18 years at the time of signing the informed consent form. Because no dosing or adverse event data are currently available on the use of everolimus in combination with lenalidomide in patients \< 18 years of age, children are excluded from this study.
• Able to adhere to the study visit schedule and other protocol requirements.
• Patients must have at least one measurable site of disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation.
• Diagnosed with advanced refractory solid malignancies or intolerant of standard therapy for the stage of the disease (because there is currently no standard approved therapy for adenoidcystic carcinoma, therefore there is no requirement of prior therapy for this patient population).
• All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study. A minimum of 6 weeks treatment break is required in case of nitrosoureas or mitomycin C.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 at study entry.
• Able to receive prophylactic anticoagulation with aspirin, warfarin or low molecular weight heparin when required for lenalidomide administration.
• Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5 x upper limit of normal (ULN). NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
• Laboratory test results within these ranges:
• Absolute neutrophil count 1500 ≥ /mm³
• Platelet count ≥ 100,000/mm³
• Hb ≥ 9 g/dL
• Creatinine within institutional limits of normal or creatinine clearance ≥ 60 ml/min/m² if elevated creatinine

Sponsors & Collaborators

• Emory University: lead
• Celgene: collaborator
• Novartis: collaborator

Study Sites (2)

Grady Health System

Atlanta, Georgia, 30303, United States

Location

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• Harvey RD, Carthon BC, Lewis C, Hossain MS, Zhang C, Chen Z, Harris WB, Alese OB, Shaib W, Bilen MA, Lawson DH, Wu C, Steuer CE, El-Rayes BF, Khuri FR, Lonial S, Waller EK, Ramalingam SS, Owonikoko TK. Phase 1 safety and pharmacodynamic study of lenalidomide combined with everolimus in patients with advanced solid malignancies with efficacy signal in adenoid cystic carcinoma. Br J Cancer. 2020 Oct;123(8):1228-1234. doi: 10.1038/s41416-020-0988-2. Epub 2020 Jul 24.

  PMID: 32704173 DERIVED

MeSH Terms

Conditions

Neuroendocrine Tumors; Kidney Neoplasms

Interventions

Lenalidomide; Everolimus

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Sirolimus; Macrolides; Lactones

Results Point of Contact

• Title: Taofeek K. Owonikoko, MD, PhD, MSCR
• Organization: Emory University

towonik@emory.edu

404-778-1900

Study Officials

• Taofeek Owonikoko, PhD/MD

  Emory University Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Principal Investigator

Study Record Dates

• First Submitted: October 8, 2010
• First Posted: October 11, 2010
• Study Start: September 9, 2010
• Primary Completion: November 5, 2020
• Study Completion: November 5, 2020
• Last Updated: January 27, 2022
• Results First Posted: January 27, 2022

Record last verified: 2021-11

Locations

US (2)