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

Millennium Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Hematologic Malignancies; Advanced Solid Malignancies

Treatments: Drug: paclitaxel; Drug: trastuzumab; Drug: MLN0128

Study type: Interventional

Funder types: Industry

Identifiers

NCT01351350

INK128-003

U1111-1181-8192 (Other Identifier)

Details and patient eligibility

About

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.

Full 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

Enrollment: 68 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Please note that there are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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68 participants in 10 patient groups

MLN0128P 30 mg QW

Experimental group

Description:

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.

Treatment:

Drug: MLN0128

Drug: paclitaxel

MLN0128P 40 mg QW

Experimental group

Description:

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.

Treatment:

Drug: MLN0128

Drug: paclitaxel

MLN0128P 6 mg QD×3d QW

Experimental group

Description:

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.

Treatment:

Drug: MLN0128

Drug: paclitaxel

MLN0128P 7 mg QD×3d QW

Experimental group

Description:

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.

Treatment:

Drug: MLN0128

Drug: paclitaxel

MLN0128P 8 mg QD×3d QW

Experimental group

Description:

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.

Treatment:

Drug: MLN0128

Drug: paclitaxel

MLN0128P 9 mg QD×3d QW

Experimental group

Description:

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.

Treatment:

Drug: MLN0128

Drug: paclitaxel

MLN0128P 10 mg QD×3d QW

Experimental group

Description:

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.

Treatment:

Drug: MLN0128

Drug: paclitaxel

MLN0128P 7 mg QD×5d QW

Experimental group

Description:

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.

Treatment:

Drug: MLN0128

Drug: paclitaxel

MLN0128P 8 mg QD×3d QW HER2-

Experimental group

Description:

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.

Treatment:

Drug: MLN0128

Drug: paclitaxel

MLN0128PH 8 mg QD×3d QW HER2+

Experimental group

Description:

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.

Treatment:

Drug: MLN0128

Drug: paclitaxel

Drug: trastuzumab