This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

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

This study is currently recruiting participants.
See Contacts and Locations
Verified May 2017 by Takeda ( Millennium Pharmaceuticals, Inc. )
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier:
NCT02724020
First received: March 25, 2016
Last updated: May 10, 2017
Last verified: May 2017
  Purpose
This study will 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.

Condition Intervention Phase
Clear-cell Metastatic Renal Cell Carcinoma Drug: Everolimus Drug: MLN0128 Drug: MLN1117 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Takeda ( Millennium Pharmaceuticals, Inc. ):

Primary Outcome Measures:
  • Progression-Free survival (PFS) [ Time Frame: From first dose of study drug to disease progression or death (approximately 3 years) ]
    PFS is defined as the time from the date of randomization to the date of first documentation of Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 or death due to any cause, whichever occurs first. For a participant whose disease has not progressed and is last known to be alive, PFS will be censored at the last response assessment that is Stable Disease (SD) or better. PD is 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.


Secondary Outcome Measures:
  • Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: From first dose of study drug through 30 days after the last dose of study drug (up to 27 months) ]
    An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

  • Overall survival (OS) [ Time Frame: From first dose of study drug to death (approximately 3 Years) ]
    Overall survival is defined as the time from the date of randomization to the date of death. Participants without documentation of death at the time of analysis will be censored at the date last known to be alive.

  • Time-to-progression (TTP) [ Time Frame: From first dose of study drug until disease progression, or death which occurs first (approximately 3 Years) ]
    Time-to-progression is defined as the time from the date of randomization to the date of first documentation of PD. For a participant whose disease has not progressed, TTP will be censored at the last response assessment that is Stable Disease or better. PD is 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.

  • Objective Response Rate (ORR) [ Time Frame: From first dose of study drug until discontinuation of study drug due to disease progression, unacceptable toxicity, or death which occurs first (approximately 24 months) ]
    ORR is defined as the percentage of participants who achieve a best response of complete response (CR) or partial response (PR) according to RECIST Version 1.1. CR is defined as the disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR is defined as at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the Baseline sum LD.

  • Clinical Benefit Rate (CBR) [ Time Frame: From first dose study drug until discontinuation of study drug due to disease progression, unacceptable toxicity, or death which occurs first (approximately 24 months) ]
    CBR is defined as the percentage of participants who achieve a best response of complete response (CR), partial response (PR) or stable disease (SD) according to RECIST Version 1.1 and will be reported for both CBR with any duration SD and CBR with SD duration of at least 4 months. CR is defined as the disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR is defined as at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the Baseline sum LD. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.


Estimated Enrollment: 189
Actual Study Start Date: June 30, 2016
Estimated Study Completion Date: November 30, 2020
Estimated Primary Completion Date: March 30, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Everolimus 10 mg
Everolimus 10 mg, capsules, orally, once daily (QD) in a 28-day cycle until disease progression, unacceptable toxicity, consent withdrawal, or death up to 24 months, or longer upon discussion with the investigator and the sponsor if the patient is believed that the patient would derive benefit.
Drug: Everolimus
Everolimus capsules
Experimental: MLN0128 30 mg
MLN0128 30 mg, capsules, orally, once weekly (QW) on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression, unacceptable toxicity, consent withdrawal, or death up to 24 month or longer upon discussion with the investigator and the sponsor if the patient is believed that the patient would derive benefits.
Drug: MLN0128
MLN0128 capsules
Other Names:
  • TAK-228
  • INK0128
Experimental: MLN0128 4 mg + MLN1117 200 mg
MLN0128 4 mg, capsules, orally, QD 3 days per week and MLN1117 200 mg, capsules, orally, QD 3 days per week on Days 1-3, 8-10, 15-17 and 22-24 of a 28-day cycle until disease progression, unacceptable toxicity, consent withdrawal, or death up to 24 months or longer upon discussion with the investigator and the sponsor if the patient is believed that the patient would derive benefit.
Drug: MLN0128
MLN0128 capsules
Other Names:
  • TAK-228
  • INK0128
Drug: MLN1117
MLN1117 capsules
Other Names:
  • TAK-117
  • INK1117

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

  • Everolimus 10 mg once daily (QD)
  • MLN0128 30 mg once weekly (QW)
  • MLN0128 4 mg + MLN1117 200 mg QD x 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female participants aged 18 years or older.
  2. Histologically confirmed renal cell carcinoma with a clear-cell component.
  3. Evidence that the renal cell carcinoma is advanced or metastatic.
  4. Radiologic evidence of progressive disease (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.
  5. 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).
  6. Karnofsky Performance Status (KPS) ≥70%.
  7. Life expectancy of ≥3 months.
  8. 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 labeling [eg, 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 [eg, 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 (ie, 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 labeling [eg, 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 [eg, 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.
  9. Suitable venous access for the study-required blood sampling.
  10. Screening clinical laboratory values:

    • Absolute neutrophil count ≥ 2000/μL and platelet count ≥100,000/μL;
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 X the upper limit of normal (ULN);
    • Total bilirubin ≤ 1.5 X ULN;
    • Estimated creatinine clearance by Cockcroft-Gault ≥40 mL/min/1.73m^2;
    • Glycosylated hemoglobin (HbA1c) <7.0%, fasting serum glucose ≤ 130 mg/dL, and fasting triglycerides ≤ 300 mg/dL.
  11. At least 14 days since the end of prior systemic VEGF-targeted treatment (ie, 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.
  12. At least 21 days since the last dose of bevacizumab, other antibody, or interferon.
  13. 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.

Exclusion Criteria:

  1. Central nervous system (CNS) metastasis.
  2. 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.
  3. Known human immunodeficiency virus infection.
  4. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection.
  5. Treatment with strong inhibitors and/or inducers of cytochrome P450 (CYP) 3A4, CYP2C9, or CYP2C19 within 1 week preceding the first dose of study drug.
  6. 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.
  7. Women who are either breast feeding or pregnant.
  8. 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.
  9. Significant active cardiovascular or pulmonary disease including:

    • Uncontrolled hypertension (ie, either systolic blood pressure >160 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; eg, repeated demonstration of QTc interval >480 ms, or history of congenital, long-QT syndrome, or torsades de pointes).
  10. 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.
  11. Prior therapy with agents that target PI3K, AKT, or mTOR. Participants with known hypersensitivity to everolimus or rapamycin derivatives are also excluded.
  12. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
  13. Participants requiring daily or chronic use of a proton pump inhibitor (PPI) and/or having taken a PPI within 7 days before receiving the first dose of study drug.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02724020

Contacts
Contact: Medical Information Call Center +1-844-662-8532 GlobalOncologyMedinfo@takeda.com

  Show 51 Study Locations
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Director: Medical Director Clinical Science Takeda
  More Information

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02724020     History of Changes
Other Study ID Numbers: C31005
2015-002133-22 ( EudraCT Number )
U1111-1172-1808 ( Registry Identifier: WHO )
Study First Received: March 25, 2016
Last Updated: May 10, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Takeda ( Millennium Pharmaceuticals, Inc. ):
Drug Therapy

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Everolimus
Sirolimus
Endothelial Growth Factors
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Growth Substances

ClinicalTrials.gov processed this record on June 22, 2017