Study of the drug substances MLN0128 and MLN0128+MLN1117 Compared WithEverolimus in the Treatment of Patients with metastatic clear cell renal carcinoma

Phase 1

• Conditions: metastatic clear-cell renal cell carcinoma (mccRCC); MedDRA version: 21.1Level: PTClassification code 10050018Term: Renal cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10038407Term: Renal cell cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-002133-22-PL
• Lead Sponsor: Millenium Pharmaceuticals, a wholly owned subsidiary of Takeda pharmaceutical Company Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-05-29
• Last Update Posted: 21 July 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 189

Inclusion Criteria

Each patient must meet all of the following inclusion criteria to be enrolled in the study.
1. Male or female patients 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. Patients may also have received prior therapies with interferon, IL-2, anti-PD1 antibodies, cabozantinib, or other experimental agents, but not prior therapy with any agent that targets PI3K, AKT, or mTOR.
6. Karnofsky Performance Status (KPS) =70% (refer to Appendix D).
7. Life expectancy of =3 months.
8. Female patients 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 (See Appendix E), at the same time, from the time of signing the informed consent through 90 days (or longer, as mandated by local labeling [eg, USPI, 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 patient. (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 patients, 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 patient. (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 as specified below:
? Absolute neutrophil count ?2000/?L and platelet count ?100,000/?L.
? Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ?2.5?the upper limit of normal (ULN).
? Total bilirubin ?1.5?ULN.
? Estimated creatinine clearance by Cockcroft-Gault =40 mL/min/1.73m2 (see Appendix F).
? 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 (NCI CTCAE Version 4.03) or to Baseline.
12. At least 21 days since

Exclusion Criteria

Patients meeting any of the following exclusion criteria are not to be enrolled in the study.
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 patient’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. Manifestations of malabsorption due to prior GI surgery, GI disease, or for an unknown reasonthat may alter the absorption of everolimus, MLN0128, or MLN1117. In addition, patients with enteric stomata are excluded.
6. Women who are either breast feeding or pregnant.
7. 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 (see Appendix G). Pulmonary embolism.
8. Significant active cardiovascular or pulmonary disease including:
? Uncontrolled hypertension (ie, either systolic blood pressure >160 mm Hg or 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 msec, or history of congenital, long-QT syndrome, or torsades de pointes).
9. 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. Patients 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.
10. Prior therapy with agents that target PI3K, AKT, or mTOR. Patients with known hypersensitivity to everolimus or rapamycin derivatives are also excluded.
11. Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol.
12. Patients who have taken a PPI within 3 days before receiving the
first dose of study drug.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified