Phase 1
Completed N=68
Dose Escalation Study of MLN0128 in Combination With Paclitaxel, With/Without Trastuzumab, in Subjects With Advanced Solid Malignancies
Source: ClinicalTrials.gov NCT01351350 ↗Enrolled (actual)
68
Serious AEs
44.8%
Results posted
Aug 2019
Primary outcomePrimary: Dose Escalation Phase: Maximum Tolerated Dose (MTD) — 8 mg (QD×3d QW)
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Dose Escalation Phase: Maximum Tolerated Dose (MTD) |
8 | — |
| PRIMARY Dose Escalation Phase: Number of Participants With at Least 1 Dose Limiting Toxicity (DLT) |
0; 2; 0; 0; 0; 2 | — |
| PRIMARY Objective Response Rate (ORR) |
0; 9; 44; 10; 20 | — |
| PRIMARY Percentage of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events(SAEs), AEs Resulting in Discontinuation of MLN0128 and Fatal AEs Within 30 Days of Last Dose of Study Drug |
100; 100; 100; 100; 100; 63 | — |
| SECONDARY Cmax: Maximum Observed Plasma Concentration for MLN0128 |
245.0; 345.5; 26.7; 31.1; 41.8; 34.2 | — |
| SECONDARY Cmin: Minimum Observed Plasma Concentration for MLN0128 |
— | — |
| SECONDARY Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN0128 |
3.0; 3.0; 2.0; 3.0; 5.6; 4.1 | — |
| SECONDARY Terminal Phase Elimination Half-life (T1/2) for MLN0128 |
6.6; 7.2 | — |
| SECONDARY AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MLN0128 |
206.5; 286.0 | — |
| SECONDARY AUC(0-6): Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours for MLN0128 |
753.7; 1325.0; 104.4; 121.7; 139.9; 146.2 | — |
| SECONDARY Cmax: Maximum Observed Plasma Concentration for Paclitaxel |
2538.0; 2355.0; 1933.3; 1942.5; 1620.0; 3798.3 | — |
| SECONDARY Cmin: Minimum Observed Plasma Concentration for Paclitaxel |
— | — |
| SECONDARY Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Paclitaxel |
1.1; 1.1; 1.1; 1.2; 1.2; 1.1 | — |
| SECONDARY Terminal Phase Elimination Half-life (T1/2) for Paclitaxel |
10.0; 9.1; 9.6; 9.3 | — |
| SECONDARY AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Paclitaxel |
4590.0; 4790.0; 5002.0; 5485.0 | — |
| SECONDARY AUC(0-6): Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours for Paclitaxel |
3198.3; 3515.0; 2620.0; 3157.5; 2683.3; 5315.0 | — |
| SECONDARY AUC(0-24): Area Under the Plasma Concentration-time Curve Extrapolated to 24 Hours for Paclitaxel |
3583.3; 4332.5; 6415.0; 5135.0 | — |
| SECONDARY CL: Total Clearance Calculated Using the Observed Value of the Last Quantifiable Concentration for Paclitaxel |
36.2; 34.8; 31.2; 25.8 | — |
| SECONDARY Vss: Volume of Distribution at Steady State Calculated Using the Observed Value of the Last Quantifiable Concentration for Paclitaxel |
313.5; 262.0; 252.2; 150.0 | — |
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
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
Data sourced from ClinicalTrials.gov (NCT01351350). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.