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Clear-cell Metastatic Renal Cell CarcinomaPhase 2NCT02724020

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

A Phase 2 study testing Everolimus, MLN0128 and MLN1117 in people with Clear-cell Metastatic Renal Cell Carcinoma, run by Millennium Pharmaceuticals, Inc. at 36 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Everolimus, MLN0128 and MLN1117
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
96 participants
Where
36 sitesin 8 countries
Study dates
30 Jun 2016to 13 Oct 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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%.
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  • 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.).
  • Agree not to donate sperm during the course of this study or within 120 days after receiving their last dose of study drug.
  • Suitable venous access for the study-required blood sampling.
  • Screening clinical laboratory values:
  • Absolute neutrophil count >=2000 per microliter (/mcL) and platelet count >=100,000/mcL;
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to (<=) 2.5*the upper limit of normal (ULN);
  • Total bilirubin <=1.5*ULN;
  • Estimated creatinine clearance by Cockcroft-Gault >=40 milliliter per minute (mL/min) / 1.73 square meter (m^2);
  • Glycosylated hemoglobin (HbA1c) less than (<) 7.0%, fasting serum glucose <=130 milligram per deciliter (mg/dL), and fasting triglycerides <=300 mg/dL.
  • At least 14 days since the end of prior systemic VEGF-targeted treatment (that is, sunitinib, pazopanib, axitinib, or sorafenib), radiotherapy, or surgical procedure with resolution of all treatment-related toxicity (except alopecia and hypothyroidism) either to Grade 0 or 1 (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 4.03) or to baseline.
  • At least 21 days since the last dose of bevacizumab, other antibody, or interferon.
  • Voluntary written consent given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.

Who cannot join

  • 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.
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  • 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;
  • Pulmonary hypertension.
  • Uncontrolled asthma or oxygen saturation <90% by arterial blood gas analysis or pulse oximetry on room air.
  • Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention; or history of valve replacement.
  • Medically significant (symptomatic) bradycardia.
  • History of arrhythmia requiring an implantable cardiac defibrillator.
  • Baseline prolongation of the rate-corrected QT interval (QTc; example, repeated demonstration of QTc interval >480 millisecond [ms], or history of congenital, long-QT syndrome, or torsades de pointes).
  • Diagnosed or treated for another malignancy within 2 years before administration of the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer, superficial bladder cancer, very low risk prostate on observation, or carcinoma in situ of any type are not excluded if they have undergone complete resection.
  • Prior therapy with agents that target Phosphatidylinositide 3-kinases (PI3K), Protein kinase B (AKT), or mechanistic target of rapamycin (mTOR). Participants with known hypersensitivity to everolimus or rapamycin derivatives are also excluded.
  • Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
  • Participants who have taken a proton pump inhibitor (PPI) within 3 days before receiving the first dose of study drug.

Trial locations and contacts

36 sites in 8 countries.

36 sites in 8 countries

United States7 sites

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

    Columbus, Ohio, 43210

  • Hackensack University Medical Center PARTNER

    Hackensack, New Jersey, 07601

  • USC Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Tennessee Oncology

    Nashville, Tennessee, 37203

  • Florida Cancer Specialists-Broadway

    Venice, Florida, 33916

  • The Center for Cancer and Blood Disorders

    Weatherford, Texas, 76086

  • Florida Cancer Specialists

    West Palm Beach, Florida, 33401

Other trials in United States

Spain7 sites

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Hospital Clinic i Provincial de Barcelona

    Barcelona, 08036

  • Hospital Duran i Reynals

    L'Hospitalet de Llobregat, Barcelona, 08023

  • MD Anderson Cancer Centre

    Madrid, 28033

  • Hospital Universitario Ramon Y Cajal

    Madrid, 28034

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Universitario Virgen del Rocio

    Seville, 41013

Other trials in Spain

United Kingdom6 sites

  • Lancashire Teaching Hospitals NHS Foundation Trust

    Blackburn, England, BB2 3HH

  • Velindre Cancer Centre

    Cardiff, South Glamorgan, CF14 2TL

  • Royal Devon and Exeter Hospital (Wonford)

    Exeter, Devon, EX2 5DW

  • Royal Surrey County Hospital

    Guildford, Surrey, GU2 7XX

  • Barts Hospital

    London, Greater London, EC1M 6BQ

  • The Christie

    Manchester, Greater Manchester, M20 4BX

Other trials in United Kingdom

France5 sites

  • Institut de Cancerologie de l'Ouest Paul Papin

    Angers, Pays de la Loire Region, 49933

  • Groupe Hospitalier Saint Andre - Hopital Saint Andre

    Bordeaux, Aquitaine, 33075

  • Clinique Victor Hugo - Centre Jean Bernard

    Le Mans, Sarthe, 72015

  • Groupe Hospitalier Pitie-Salpetriere

    Paris, Paris, 75651

  • ICL-Alexis Vautrin, Departement dOncologie Medicale

    Vandœuvre-lès-Nancy, Meurthe Et Moselle, 54511

Other trials in France

Italy4 sites

  • Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi

    Bologna, 40138

  • Istituto Nazionale Tumori Fondazione G. Pascale

    Naples, 80131

  • IOV - Istituto Oncologico Veneto IRCCS

    Padova, 35128

  • Fondazione IRCCS Policlinico San Matteo

    Pavia, 27100

Other trials in Italy

Czechia3 sites

  • Fakultni nemocnice u sv. Anny v Brne

    Brno, 656 91

  • Fakultni nemocnice Olomouc

    Olomouc, 775 20

  • Fakultni nemocnice v Motole

    Prague, 150 06

Other trials in Czechia

Canada2 sites

  • McMaster University

    Hamilton, Ontario, L8N 4A6

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

Poland2 sites

  • Beskidzkie Centrum Onkologii im.Jana Pawla II

    Bielsko-Biala, 43-300

  • Instytut MSF, Ulica Pilota Stanislawa Wigury 19

    Lodz, 90-302

Other trials in Poland

About this study

Official title: A Phase 2, Open-label Study to Evaluate the Efficacy and Safety of Single-Agent MLN0128 and the Combination of MLN0128+MLN1117 Compared With Everolimus in the Treatment of Adult Patients With Advanced or Metastatic Clear-Cell Renal Cell Carcinoma That Has Progressed on Vascular Endothelial Growth Factor-Targeted Therapy

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.

Read the detailed description

The drugs being tested in this study are called MLN0128 and MLN1117. MLN0128 and MLN1117 are being tested to treat people who have mccRCC. This study will assess the efficacy and safety of MLN0128 and MLN1117 as well as how it is processed by the body in participants with advanced or mccRCC.

The study will enroll approximately 96 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the three treatment groups:

  • Everolimus 10 mg once daily
  • MLN0128 30 mg once weekly
  • MLN0128 4 mg once daily for 3 days per week + MLN1117 200 mg once daily for 3 days per week

All participants will be asked to take the study drug at the same time on each scheduled day.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is 2 years after last participant is randomized, or when the last participant discontinues study treatment (approximately 3 years). Participants will make multiple visits to the clinic including a follow-up visit 30 to 40 days after receiving their last dose of study drug or prior to start of subsequent anticancer therapy for safety assessment. Participants will then be followed for Progression Free and Overall Survival.

Being tested
Everolimus, MLN0128, MLN1117
Keywords
Drug therapy
Medical subject headings
Clear-cell metastatic renal cell carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EverolimusDrug

    Everolimus capsules.

  • MLN0128Drug

    Also called TAK-228, INK0128

    MLN0128 capsules.

  • MLN1117Drug

    Also called TAK-117, INK1117

    MLN1117 capsules.

Study groups in NCT02724020
Study groupRoleWhat they receive
Arm A: Single-agent Everolimus 10 mg QDActive comparatorEverolimus 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).
Receives: Drug: Everolimus
Arm B: Single-agent MLN0128 30 mg QWExperimentalMLN0128 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).
Receives: Drug: MLN0128
Arm C: Combination of MLN0128 4 mg QD + MLN1117 200 mg QDExperimentalMLN0128 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).
Receives: Drug: MLN0128; Drug: MLN1117

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (6)

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

    An AE was defined as any untoward medical occurrence in participants administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. TEAE was defined as the event that occur after administration of the first dose of study drug and through 30 days after the last dose of study drug.

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

  2. Overall Survival (OS)

    Overall survival in months was defined as the time from the date of randomization to the date of death.

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

  3. Time-to-progression (TTP)

    TTP in months is defined as the time from the date of randomization to the date of first documentation of progression. Per RECIST v1.1, PD was defined as at least a 20% increase in the sum of the 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.

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

  4. Objective Response Rate (ORR)

    ORR was defined as the percentage of participants among response evaluable analysis set who achieve a best overall response of complete response (CR) or partial response (PR) based on investigators assessment of response following RECIST 1.1. CR was defined as disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions.

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

  5. Clinical Benefit Rate (CBR)

    CBR is defined as the percentage of participants who achieve a best response of CR, PR or stable disease (SD) of any duration. CR was defined as disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

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

  6. CBR With SD Duration of at Least 16 Weeks

    CBR with SD duration of at least 4 months (CBR-16) was defined as the percentage of participants who achieve CR or PR of any duration or have SD with duration of at least 16 weeks. CR was defined as disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

    Measured: Up to Week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Mar 2016 (estimated)
  2. Study start30 Jun 2016
  3. Primary completion3 Feb 2020
  4. Study completion13 Oct 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
96 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02724020
Sponsor's protocol ID
C31005
Other IDs
2015-002133-22, U1111-1172-1808, 2015
Status last verified
Nov 2021
First submitted
25 Mar 2016
Last updated
19 Nov 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Everolimus, MLN0128 and MLN1117 in people with Clear-cell Metastatic Renal Cell Carcinoma, run by Millennium Pharmaceuticals, Inc. at 36 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 36 sites in United States, Spain, United Kingdom, France, Italy and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-Free Survival (PFS) (time frame: From first dose of study drug up to disease progression or death, assessed up to 43 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02724020.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2021.

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