MLN0128 and MLN0128 + MLN1117 Compared With Everolimus in the Treatment of Adults With Advanced or Metastatic Clear-Cell Renal Cell Carcinoma

NCT02724020 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: C310052015-002133-22U1111-1172-1808
• Study Type: interventional
• Target: 96
• Locations: 8 countries
• Sites: 36

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of single-agent MLN0128 and the combination of MLN0128 + MLN1117 compared with everolimus in the treatment of participants with metastatic clear-cell renal cell carcinoma (mccRCC) that have progressed on vascular endothelial growth factor (VEGF)-targeted therapy.

Conditions

Clear-cell Metastatic Renal Cell Carcinoma

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  PFS was defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) or death due to any cause, whichever occurs first. Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

  From first dose of study drug up to disease progression or death, assessed up to 43 months

Secondary Outcomes (6)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  From first dose of study drug through 30 days after the last dose of study drug (approximately up to 31 months)

• Overall Survival (OS)

  From first dose of study drug through 30 days after the last dose of study drug (up to 51 months)

• Time-to-progression (TTP)

  From first dose of study drug up to disease progression or death (up to 51 months)

• Objective Response Rate (ORR)

  From first dose of study drug to disease progression or death (up to 51 months)

• Clinical Benefit Rate (CBR)

  From first dose of study drug up to disease progression or death (up to 51 months)

Study Arms (3)

Arm A: Single-agent Everolimus 10 mg QD

ACTIVE COMPARATOR

Everolimus 10 mg capsules, orally, once daily in a 28-day treatment cycle until disease progression, consent withdrawal, death, or transfer to the Post-trial Access (PTA) program (Median duration of treatment was 15.43 weeks up to end of study).

Drug: Everolimus

Arm B: Single-agent MLN0128 30 mg QW

EXPERIMENTAL

MLN0128 30 mg capsules, orally, once weekly on Days 1, 8, 15, and 22 of a 28-day treatment cycle until disease progression, unacceptable toxicity, consent withdrawal, death, or transfer to the PTA program (Median duration of treatment was 9.64 weeks up to end of study).

Drug: MLN0128

Arm C: Combination of MLN0128 4 mg QD + MLN1117 200 mg QD

EXPERIMENTAL

MLN0128 4 mg and MLN1117 200 mg capsules, orally, both once daily for 3 days per week (QD X 3) on Days 1-3, 8-10, 15-17, and 22-24 of a 28-day treatment cycle until disease progression, unacceptable toxicity, consent withdrawal, death, or transfer to the PTA program (Median duration of treatment was 9.43 weeks up to end of study).

Drug: MLN0128; Drug: MLN1117

Interventions

Everolimus DRUG

Everolimus capsules.

Arm A: Single-agent Everolimus 10 mg QD

MLN0128 DRUG

MLN0128 capsules.

Also known as: TAK-228, INK0128

Arm B: Single-agent MLN0128 30 mg QW; Arm C: Combination of MLN0128 4 mg QD + MLN1117 200 mg QD

MLN1117 DRUG

MLN1117 capsules.

Also known as: TAK-117, INK1117

Arm C: Combination of MLN0128 4 mg QD + MLN1117 200 mg QD

Eligibility Criteria

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

You may qualify if:

• Male or female participants aged 18 years or older.
• Histologically confirmed renal cell carcinoma (RCC) with a clear-cell component.
• Evidence that the RCC is advanced or metastatic.
• Radiologic evidence of PD (according to RECIST Version 1.1) either during or within 6 months after stopping their most recent systemic therapy for RCC before enrollment into this study.
• At least 1, prior line of VEGF-targeted therapy, but not more than 4 total prior lines of systemic therapy. Exposure to more than 1 line of VEGF-targeted therapy is acceptable. Participants may also have received prior therapies with interferon, interleukin 2 (IL-2), anti-PD1 antibodies, cabozantinib or other experimental agents, but not prior therapy with any agent that targets phosphoinositide 3-kinase (PI3K), serine/ threonine-specific protein kinase (AKT), or mechanistic (or mammalian) target of rapamycin (mTOR).
• Karnofsky Performance Status (KPS) greater than or equal to (\>=) 70%.
• Life expectancy of \>=3 months.
• Female participants who:
• Are postmenopausal for at least 1 year before the screening visit, OR
• Are surgically sterile, OR
• If they are of childbearing potential, agree to practice 1 highly effective method of contraception, and 1 additional effective (barrier) method, at the same time, from the time of signing the informed consent through 90 days (or longer, as mandated by local labelling \[example, United States Prescribing Information (USPI), Summary of Product Characteristics (SmPC), etc;\]) after the last dose of study drug, OR
• Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence \[example, calendar, ovulation, symptothermal, postovulation methods\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.).
• Male participants, even if surgically sterilized (that is, status postvasectomy), who:
• Agree to practice highly effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study drug (or longer, as mandated by local labelling \[example, USPI, SmPC, etc\]), OR
• Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant (Periodic abstinence \[example, calendar, ovulation, symptothermal, postovulation methods for the female partner\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.).

You may not qualify if:

• Central nervous system (CNS) metastasis.
• Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active CNS disease, active infection, or any other condition that might compromise the participant's participation in the study.
• Known human immunodeficiency virus infection.
• Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection.
• Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of everolimus, MLN0128, or MLN1117. In addition, participants with enteric stomata are excluded.
• Women who are either breast feeding or pregnant.
• History of any of the following within the last 6 months before administration of the first dose of study drug
• Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures;
• Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures;
• Requirement for inotropic support (excluding digoxin), or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation, or ventricular tachycardia);
• Placement of a pacemaker for control of rhythm;
• New York Heart Association Class III or IV heart failure;
• Pulmonary embolism.
• Significant active cardiovascular or pulmonary disease including:
• Uncontrolled hypertension (that is, either systolic blood pressure greater than \[\>\] 160 millimeter of mercury \[mm Hg\]; diastolic blood pressure \>95 mm Hg). Use of anti-hypertensive agents to control hypertension before Cycle 1 Day 1 is allowed;

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (36)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Florida Cancer Specialists-Broadway

Venice, Florida, 33916, United States

Location

Florida Cancer Specialists

West Palm Beach, Florida, 33401, United States

Location

Hackensack University Medical Center PARTNER

Hackensack, New Jersey, 07601, United States

Location

The Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital

Columbus, Ohio, 43210, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

The Center for Cancer and Blood Disorders

Weatherford, Texas, 76086, United States

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

McMaster University

Hamilton, Ontario, L8N 4A6, Canada

Location

Fakultni nemocnice u sv. Anny v Brne

Brno, 656 91, Czechia

Location

Fakultni nemocnice Olomouc

Olomouc, 775 20, Czechia

Location

Fakultni nemocnice v Motole

Prague, 150 06, Czechia

Location

Groupe Hospitalier Saint Andre - Hopital Saint Andre

Bordeaux, Aquitaine, 33075, France

Location

ICL-Alexis Vautrin, Departement dOncologie Medicale

Vandœuvre-lès-Nancy, Meurthe Et Moselle, 54511, France

Location

Groupe Hospitalier Pitie-Salpetriere

Paris, Paris, 75651, France

Location

Institut de Cancerologie de l'Ouest Paul Papin

Angers, Pays de la Loire Region, 49933, France

Location

Clinique Victor Hugo - Centre Jean Bernard

Le Mans, Sarthe, 72015, France

Location

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi

Bologna, 40138, Italy

Location

Istituto Nazionale Tumori Fondazione G. Pascale

Napoli, 80131, Italy

Location

IOV - Istituto Oncologico Veneto IRCCS

Padua, 35128, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Beskidzkie Centrum Onkologii im.Jana Pawla II

Bielsko-Biala, 43-300, Poland

Location

Instytut MSF, Ulica Pilota Stanislawa Wigury 19

Lodz, 90-302, Poland

Location

Hospital Duran i Reynals

L'Hospitalet de Llobregat, Barcelona, 08023, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, 08036, Spain

Location

MD Anderson Cancer Centre

Madrid, 28033, Spain

Location

Hospital Universitario Ramon Y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Royal Devon and Exeter Hospital (Wonford)

Exeter, Devon, EX2 5DW, United Kingdom

Location

Lancashire Teaching Hospitals NHS Foundation Trust

Blackburn, England, BB2 3HH, United Kingdom

Location

Barts Hospital

London, Greater London, EC1M 6BQ, United Kingdom

Location

The Christie

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

Velindre Cancer Centre

Cardiff, South Glamorgan, CF14 2TL, United Kingdom

Location

Royal Surrey County Hospital

Guildford, Surrey, GU2 7XX, United Kingdom

Location

MeSH Terms

Conditions

Clear-cell metastatic renal cell carcinoma

Interventions

Everolimus; sapanisertib; serabelisib

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2016
• First Posted: March 31, 2016
• Study Start: June 30, 2016
• Primary Completion: February 3, 2020
• Study Completion: October 13, 2020
• Last Updated: November 19, 2021
• Results First Posted: February 21, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

IT (4); GB (6); PL (2); ES (7); US (7); CZ (3); FR (5); CA (2)