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
Overview
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 96
- Locations
- 36
- Primary Endpoint
- Progression-Free Survival (PFS)
Overview
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.
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- •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 MLN
- •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;
Arms & Interventions
Arm A: Single-agent Everolimus 10 mg QD
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).
Intervention: Everolimus (Drug)
Arm B: Single-agent MLN0128 30 mg QW
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).
Intervention: MLN0128 (Drug)
Arm C: Combination of MLN0128 4 mg QD + MLN1117 200 mg QD
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).
Intervention: MLN0128 (Drug)
Arm C: Combination of MLN0128 4 mg QD + MLN1117 200 mg QD
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).
Intervention: MLN1117 (Drug)
Outcomes
Primary Outcomes
Progression-Free Survival (PFS)
Time Frame: From first dose of study drug up to disease progression or death, assessed up to 43 months
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.
Secondary Outcomes
- 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))
- Objective Response Rate (ORR)(From first dose of study drug to disease progression or death (up to 51 months))
- CBR With SD Duration of at Least 16 Weeks(Up to Week 16)
- Time-to-progression (TTP)(From first dose of study drug up 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))