Dose Escalation Study of MLN0128 in Participants With Advanced Malignancies

NCT ID: NCT01058707

Last Updated: 2020-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 198 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-04
• Study Completion Date: 2019-02-07

Brief Summary

This is a Phase I, open label, Dose Escalation study of oral administration of single agent MLN0128 in participants with Advanced Malignancies followed by an Expansion Phase in participants with renal cell carcinoma, endometrial cancer or urothelial cancer who have measurable disease.

Detailed Description

The drug being tested in this study is called MLN0128. MLN0128 is being tested to treat people who have Advanced Malignancies.

The study enrolled approximately 198 patients. Participants were assigned to one of the following dose regimens in the Dose Escalation Phase to establish the Maximum Tolerated Dose (MTD):

• MLN0128 QD
• MLN0128 QW
• MLN0128 QDx3dQW
• MLN0128 QDx5dQW

MLN0128 capsule, orally, once daily (QD) or Once weekly (QW) in the Dose Escalation Phase until MTD was established.

Once MTD was determined, participants were then enrolled in the Dose Expansion Phase to receive:

• MLN0128 5 mg QD
• MLN0128 30 mg QW
• MLN0128 40 mg QW

This multi-centre trial was conducted worldwide. The overall time to participate in this study was approximately 244 weeks. Participants will make multiple visits to the clinic, and were contacted by telephone OR plus a final visit after last dose of study drug for a follow-up assessment.

Conditions

Advanced Solid Malignancies

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MLN0128 QD

MLN0128 2 mg, 4 mg, 6 mg or 7 mg, capsule, orally, once daily (QD) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 52.1 weeks).

Group Type: EXPERIMENTAL

MLN0128

Intervention Type: DRUG

MLN0128 capsules

MLN0128 QW

MLN0128 7 mg, 10 mg, 15 mg, 20 mg, 30 mg or 40 mg capsule, orally, once weekly (QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 139.4 weeks).

Group Type: EXPERIMENTAL

MLN0128

Intervention Type: DRUG

MLN0128 capsules

MLN0128 QDx3d QW

MLN0128 6 mg, 9 mg, 12 mg, 16 mg or 20 mg capsule, orally, once daily every 3 days a week (QDx3d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 129.4 weeks).

Group Type: EXPERIMENTAL

MLN0128

Intervention Type: DRUG

MLN0128 capsules

MLN0128 QDx5d QW

MLN0128 7 mg, 10 mg or 13 mg capsule, orally, once daily every 5 days a week (QDx5d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 161.9 weeks).

Group Type: EXPERIMENTAL

MLN0128

Intervention Type: DRUG

MLN0128 capsules

MLN0128 5 mg QD

MLN0128 5 mg, capsule, orally, QD in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 98.3 weeks).

Group Type: EXPERIMENTAL

MLN0128

Intervention Type: DRUG

MLN0128 capsules

MLN0128 30 mg QW

MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).

Group Type: EXPERIMENTAL

MLN0128

Intervention Type: DRUG

MLN0128 capsules

MLN0128 40 mg QW

MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).

Group Type: EXPERIMENTAL

MLN0128

Intervention Type: DRUG

MLN0128 capsules

Interventions

MLN0128

MLN0128 capsules

Intervention Type: DRUG

Other Intervention Names

INK128; TAK-128

Eligibility Criteria

Inclusion Criteria

• Voluntary written consent
• Locally advanced or metastatic solid tumors with the exception of primary brain tumor, and have failed standard of care therapy
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Ability to swallow oral medications
• For women of child-bearing potential, negative serum or urine pregnancy test within 14 days prior to the first study drug administration and use of physician-approved method of birth control from 30 days prior to 90 days following the last study drug administration
• Male participants must be surgically sterile or must agree to use physician-approved contraception during the study and for 90 days following the last study drug administration
• Clinical laboratory values as specified in the protocol

Additionally, to be eligible for the Dose Expansion portion of the study:

• Participants must have evidence of measurable disease per response evaluation criteria in solid tumors (RECIST) version 1.1 by radiographic techniques or magnetic resonance imaging
• Participants must have a pathologic diagnosis of advanced or recurrent endometrial adenocarcinoma and must have failed at least 1 prior line of standard chemotherapy
• Participants must have a pathologic diagnosis of advanced/metastatic urothelial cancer (carcinoma of the bladder, ureter, and/or renal pelvis) and must have failed at least 1 line of prior therapy in the metastatic/unresectable setting
• Participants must have a pathologic diagnosis of advanced renal cell carcinoma (RCC), with histological or cytological confirmation of RCC and must have failed at least 1 prior line of anti-vascular endothelial growth factor therapy (VEGF) therapy (including but not limited to sunitinib, and/or sorafenib, and/or bevacizumab and/or pazopanib, and/or axitinib) and must not have received prior therapy with a target of rapamycin complex 1 (TORC1) inhibitor (such as temsirolimus or everolimus); or
• Participants must have a pathologic diagnosis of advanced renal cell carcinoma (RCC) and must have progressed on treatment with a TORC1 inhibitor (such as temsirolimus or everolimus).

Exclusion Criteria

• Diagnosis of primary brain tumor
• Have received prior cancer or other investigational therapy within 2 weeks prior to the first administration of study drug
• Known impaired cardiac function or clinically significant cardiac disease
• Known treatment with systemic corticosteroid within one week prior to the first administration of study drug
• Diabetes mellitus
• Human immunodeficiency virus (HIV) infection
• Known active cardiovascular disease condition as specified in protocol
• Failed to recover from the reversible effects of prior anticancer therapies
• Pregnancy (positive serum or urine pregnancy test) or breast feeding
• Malabsorption due to prior gastrointestinal (GI) surgery, GI disease
• Other clinically significant co-morbidities

Site personnel will explain the trial in detail and answer any question you may have if you do qualify for the study. You can then decide whether or not you wish to participate. If you do not qualify for the trial, site personnel will explain the reasons.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

Scottsdale, Arizona, United States

Los Angeles, California, United States

Miami, Florida, United States

Sarasota, Florida, United States

Indianapolis, Indiana, United States

Boston, Massachusetts, United States

Ann Arbor, Michigan, United States

Detroit, Michigan, United States

Buffalo, New York, United States

New York, New York, United States

Cleveland, Ohio, United States

Oklahoma City, Oklahoma, United States

Philadelphia, Pennsylvania, United States

Nashville, Tennessee, United States

Barcelona, , Spain

Valencia, , Spain

Countries

United States; Spain

References

Voss MH, Gordon MS, Mita M, Rini B, Makker V, Macarulla T, Smith DC, Cervantes A, Puzanov I, Pili R, Wang D, Jalal S, Pant S, Patel MR, Neuwirth RL, Enke A, Shou Y, Sedarati F, Faller DV, Burris HA 3rd. Phase 1 study of mTORC1/2 inhibitor sapanisertib (TAK-228) in advanced solid tumours, with an expansion phase in renal, endometrial or bladder cancer. Br J Cancer. 2020 Nov;123(11):1590-1598. doi: 10.1038/s41416-020-01041-x. Epub 2020 Sep 11.

Reference Type: DERIVED

PMID: 32913286 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2009-017284-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1187-4258

Identifier Type: OTHER

Identifier Source: secondary_id

INK128-001

Identifier Type: -

Identifier Source: org_study_id