Dose Escalation Study of MLN0128 in Combination With Paclitaxel, With/Without Trastuzumab, in Subjects With Advanced Solid Malignancies

NCT ID: NCT01351350

Last Updated: 2019-08-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2017-09-15

Brief Summary

This is a Phase I, open label, dose escalation study of oral administration of MLN0128 in combination with paclitaxel, with/without trastuzumab, in participants with advanced solid malignancies.

Detailed Description

This is a Phase I, open-label study consisting of a dose escalation phase in advanced solid malignancies to determine the maximum tolerated dose (MTD) of oral administration of MLN0128 in 1 or more dosing schedules, combined with paclitaxel on Days 1, 8 and 15 of each cycle, followed by an expansion phase for further safety and preliminary efficacy.

Once the MTD is determined for each of the dosing schedules evaluated, a dose and schedule will be selected for the expansion phase, which may enroll participants into 2 arms in parallel:

• Arm A will consist of HER2- unknown cancer participants receiving MLN0128+paclitaxel
• Arm B will consist of HER2+ cancer participants receiving MLN0128+paclitaxel plus weekly trastuzumab

Conditions

Advanced Solid Malignancies; Hematologic Malignancies

Study Design

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

Study Groups

MLN0128P 30 mg QW

MLN0128 and paclitaxel (MLN0128P): MLN0128 30 mg, capsule, orally, once weekly (QW) + paclitaxel 80 mg/m\^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase.

Group Type: EXPERIMENTAL

MLN0128

Intervention Type: DRUG

MLN0128 capsules

paclitaxel

Intervention Type: DRUG

paclitaxel intravenous infusion

MLN0128P 40 mg QW

MLN0128 40 mg, capsule, orally, once a week (QW) + paclitaxel 80 mg/m\^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase.

Group Type: EXPERIMENTAL

MLN0128

Intervention Type: DRUG

MLN0128 capsules

paclitaxel

Intervention Type: DRUG

paclitaxel intravenous infusion

MLN0128P 6 mg QD×3d QW

MLN0128 6 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m\^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase.

Group Type: EXPERIMENTAL

MLN0128

Intervention Type: DRUG

MLN0128 capsules

paclitaxel

Intervention Type: DRUG

paclitaxel intravenous infusion

MLN0128P 7 mg QD×3d QW

MLN0128 7 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m\^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase.

Group Type: EXPERIMENTAL

MLN0128

Intervention Type: DRUG

MLN0128 capsules

paclitaxel

Intervention Type: DRUG

paclitaxel intravenous infusion

MLN0128P 8 mg QD×3d QW

MLN0128 8 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m\^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase.

Group Type: EXPERIMENTAL

MLN0128

Intervention Type: DRUG

MLN0128 capsules

paclitaxel

Intervention Type: DRUG

paclitaxel intravenous infusion

MLN0128P 9 mg QD×3d QW

MLN0128 9 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m\^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase.

Group Type: EXPERIMENTAL

MLN0128

Intervention Type: DRUG

MLN0128 capsules

paclitaxel

Intervention Type: DRUG

paclitaxel intravenous infusion

MLN0128P 10 mg QD×3d QW

MLN0128 10 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m\^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase.

Group Type: EXPERIMENTAL

MLN0128

Intervention Type: DRUG

MLN0128 capsules

paclitaxel

Intervention Type: DRUG

paclitaxel intravenous infusion

MLN0128P 7 mg QD×5d QW

MLN0128 7 mg, capsule, orally, once daily 5 days on/2 days off each week + paclitaxel 80 mg/m\^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase.

Group Type: EXPERIMENTAL

MLN0128

Intervention Type: DRUG

MLN0128 capsules

paclitaxel

Intervention Type: DRUG

paclitaxel intravenous infusion

MLN0128P 8 mg QD×3d QW HER2-

MLN0128 8 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m\^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in human epidermal growth factor receptor 2 negative (HER-) cancer participants until disease progression or unacceptable toxicity for up to 1 year in the Expansion Phase.

Group Type: EXPERIMENTAL

MLN0128

Intervention Type: DRUG

MLN0128 capsules

paclitaxel

Intervention Type: DRUG

paclitaxel intravenous infusion

MLN0128PH 8 mg QD×3d QW HER2+

MLN0128 + paclitaxel + trastuzumab (MLN0128PH): MLN0128 8 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m\^2, 1 hour infusion, on Days 1, 8 and 15 plus trastuzumab 4 mg/kg loading dose on Day 1 followed by 2 mg/kg, intravenous each week of a 4-week cycle in HER+ cancer participants until disease progression or unacceptable toxicity for up to 1 year in the Expansion Phase.

Group Type: EXPERIMENTAL

MLN0128

Intervention Type: DRUG

MLN0128 capsules

paclitaxel

Intervention Type: DRUG

paclitaxel intravenous infusion

trastuzumab

Intervention Type: DRUG

trastuzumab intravenous infusion

Interventions

MLN0128

MLN0128 capsules

Intervention Type: DRUG

paclitaxel

paclitaxel intravenous infusion

Intervention Type: DRUG

trastuzumab

trastuzumab intravenous infusion

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Voluntary written consent
• Locally advanced or metastatic solid tumors with the exception of primary brain tumor, and have failed or are not eligible for 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 30 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 30 days following the last study drug administration
• Clinical laboratory values as specified in the protocol
• For expansion phase (Arm A) - HER2-/unknown participants will be enrolled
• For expansion phase (Arm B) - HER2+ cancer participants will be enrolled

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
• 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 Director

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

Fort Myers, Florida, United States

Oklahoma City, Oklahoma, United States

Nashville, Tennessee, United States

Countries

United States

References

Burris HA 3rd, Kurkjian CD, Hart L, Pant S, Murphy PB, Jones SF, Neuwirth R, Patel CG, Zohren F, Infante JR. TAK-228 (formerly MLN0128), an investigational dual TORC1/2 inhibitor plus paclitaxel, with/without trastuzumab, in patients with advanced solid malignancies. Cancer Chemother Pharmacol. 2017 Aug;80(2):261-273. doi: 10.1007/s00280-017-3343-4. Epub 2017 Jun 10.

Reference Type: DERIVED

PMID: 28601972 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

U1111-1181-8192

Identifier Type: OTHER

Identifier Source: secondary_id

INK128-003

Identifier Type: -

Identifier Source: org_study_id