Metastatic Breast CancerPhase 1NCT02719691
Phase I Study of MLN0128 and MLN8237 in Patients With Advanced Solid Tumors and Metastatic Triple-negative Breast Cancer
A Phase 1 study testing Alisertib and MLN0128 in people with Metastatic Breast Cancer and Solid Tumors, run by University of Colorado, Denver at 1 site in United States.
Trial summary
This is a phase Ib study designed to evaluate the safety and toxicity of the combination of Alisertib and MLN0128 in patients with advanced solid tumors with an expansion cohort in patients with previously treated metastatic TNBC. Read more about this study
- Who is it for?
- Ages 18 to 101 years
- Conditions the study is for
- Metastatic Breast Cancer, Solid Tumors
- What is being tested?
- Alisertib and MLN0128
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteUnited States
- Study dates
- 13 May 2016to 18 Mar 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 101 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Each patient must meet all of the following inclusion criteria to be enrolled in the study:
- Male or female patients 18 years or older.
- Dose Escalation Cohort: Patients must have a diagnosis of a histologically confirmed solid tumor that is incurable and refractory to standard therapy or for which no standard therapy exists.
- Dose Expansion Cohort Group 1 and 2: Patients must have a diagnosis of histologically confirmed metastatic TNBC defined as negative for estrogen receptor, progesterone receptor and HER2. Patients must have received either adjuvant or first line chemotherapy for metastatic disease. Negative for Estrogen and Progesterone Receptor includes the following:
- Local Pathology report classifies them as negative
- Allred Score of 2 or below
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- <1% positive staining Subjects with solid tumor types other than TNBC may also be enrolled after discussion with the Sponsor. These subjects must have a diagnosis of a histologically confirmed solid tumor that is incurable and refractory to standard therapy or for which no standard therapy exists.
- Pancreatic Cancer Cohort: Patients must have a diagnosis of locally advanced or metastatic pancreatic adenocarcinoma previously treated with or not a candidate for standard of care systemic therapy. Dose Expansion Cohort Group 1 and 2: At least one tumor lesion amenable to repeat core needle biopsy or punch biopsy without unacceptable risk of a major procedural complication.
- Dose Expansion Cohort Group 1 and 2: At least one tumor lesion amenable to repeat core needle biopsy or punch biopsy without unacceptable risk of a major procedural complication.
- Eastern Cooperative Oncology Group (ECOG) performance status < 1 (See Appendix 1)
- Three weeks or 5 half-lives (whichever is shorter) from previous systemic anticancer therapy; at least 4 weeks from major surgery and recovered; at least 2 weeks from palliative radiation and recovered. No more than 450 mg/m2 cumulative dose of doxorubicin or equivalent anthracycline dose is allowed.
- All acute treatment-related toxicities from prior therapy must have resolved to Grade < 1 prior to study entry excluding alopecia.
- For women:
- Postmenopausal for at least 1 year before the screening visit, OR
- Surgically sterile, OR
- If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 90 days 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 [e.g, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.
- For men, even if surgically sterilized (ie, status post-vasectomy), they must:
- Agree to practice effective barrier contraception during the entire study treatment period and through 120 days 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 [e.g, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception
- Agree not to donate sperm during the course of this study or 120 days after receiving their last dose of study drug
- Screening clinical laboratory values as specified below:
- Bone marrow reserve consistent with: absolute neutrophil count (ANC) ≥ 1.5 x 109/L; platelet count ≥ 100 x 109/L; hemoglobin ≥ 9 g/dL. Values must be obtained without the need for myeloid growth factor support, platelet or PRBC transfusion support within 14 days.
- Hepatic: total bilirubin ≤ 1.5 x upper limit of normal (ULN), transaminases (aspartate aminotransferase/serum glutamic oxaloacetic transaminase-AST/SGOT and alanine aminotransferase/serum glutamic pyruvic transaminase-ALT/SGPT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases are present);
- Renal: Creatinine < 1.5 X ULN or creatinine clearance ≥ 50 mL/min based either on Cockroft-Gault estimate or based on urine collection (12 or 24 hour)(Appendix 2);
- Metabolic: Glycosylated hemoglobin (HbA1c)<7.0%, fasting serum glucose (≤ 130 mg/dL) and fasting triglycerides ≤ 300 mg/dL;
- For patients undergoing serial tumor biopsies, INR and activated partial thromboplastin time (PTT) must be within 1.5 X the upper limit of normal.
- Left ventricular ejection fraction (LVEF) > LLN of the institutional standard of normal as measured by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) within 4 weeks prior to first study drug administration.
- Ability to swallow oral medications.
- Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
- Patients who have a history of brain metastasis are eligible for the study provided that all the following criteria are met:
- Brain metastases which have been treated
- No evidence of disease progression for ≥ 4 weeks or hemorrhage after treatment
- Off-treatment with dexamethasone for 2 weeks before administration of the first dose of MLN0128
- No ongoing requirement for dexamethasone or anti-epileptic drugs.
Who cannot join
- Patients meeting any of the following exclusion criteria are not to be enrolled in the study:
- Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise the patient's participation in the study.
- Known human immunodeficiency virus infection.
- Radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is considered to be over 25%.
- Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen.
- Systemic infection requiring IV antibiotic therapy within 14 days preceding the first dose of study drug, or other severe infection.
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- Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection.
- Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
- 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 or carcinoma in situ of any type are not excluded if they have undergone complete resection.
- Breast feeding or pregnant.
- Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of MLN0128. In addition, patients with enteric stomata are also excluded.
- Treatment with any investigational products within 3 weeks before the first dose of study drug.
- History of any of the following within the last 6 months before administration of the first dose of the 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 (NYHA) Class III or IV heart failure (See Appendix 3)
- Pulmonary embolism
- Significant active cardiovascular or pulmonary disease including:
- Uncontrolled hypertension (i.e., systolic blood pressure >180 mm Hg, diastolic blood pressure > 95 mm Hg). Use of anti-hypertensive agents to control hypertension before Cycle1 Day 1 is allowed.
- Pulmonary hypertension
- Uncontrolled asthma or O2 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) (e.g., repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes)
- Treatment with strong inhibitors and/or inducers of cytochrome P450 (CYP) 3A4, CYP2C19 or CYP2C19 within 1 week preceding the first dose of study drug.
- Patients receiving systemic corticosteroids (either IV or oral steroids, excluding inhalers or low-dose hormone replacement therapy) within 1 week before administration of the first dose of study drug.
- Daily or chronic use of a proton pump inhibitor (PPI) and/or having taken a PPI within 7 days before receiving the first dose of study drug.
- For patients undergoing serial tumor biopsies, known bleeding diathesis or history of abnormal bleeding or require anti-coagulation therapy which cannot be interrupted for biopsy.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Cancer Center
Aurora, Colorado, 80045
About this study
Official title: A Phase Ib Study of the Combination of MLN0128 (Dual TORC1/2 Inhibitor) and MLN8237 (Aurora A Inhibitor, Alisertib) in Patients With Advanced Solid Tumors With an Expansion Cohort in Metastatic Triple-negative Breast Cancer (TNBC)
This is a phase Ib study designed to evaluate the safety and toxicity of the combination of Alisertib and MLN0128 in patients with advanced solid tumors with an expansion cohort in patients with previously treated metastatic TNBC.
Read the detailed description
The purpose of this study is to evaluate the combination of Alisertib and MLN0128 in patients with advanced solid tumors refractory to standard treatment followed by an expansion cohort of patients with metastatic TNBC with exploratory correlative studies.
- Conditions
- Metastatic Breast Cancer, Solid Tumors
- Being tested
- Alisertib, MLN0128
- Keywords
- MLN0128, Dual TORC1/2 Inhibitor, MLN8237, Aurora A inhibitor, Alisertib, Triple-Negative Breast Cancer
- Medical subject headings
- Breast Neoplasms, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlisertibDrug
Also called Dual TORC1/2 Inhibitor
Participants will receive Alisertib in the dose-escalation and the dose-expansion part of the study.
MLN0128Drug
Also called MLN8237 (Aurora A inhibitor)
Participants will receive MLN0128 in the dose-escalation and the dose-expansion part of the study.
| Study group | Role | What they receive |
|---|---|---|
| Dose level 1: Alisertib 30mg/MLNO128 1mg | Experimental | This group will receive a Dose-Escalation: Combination of MLN0128 and Alisertib using a standard 3 + 3 design. The starting dose of Alisertib is 30 mg given PO twice daily (BID) Days 1-7 repeat every 21 days. The starting dose for MLN0128 is 1 mg given by mouth (PO) once daily with continuous dosing.
Alisertib: Participants will receive Alisertib in the dose-escalation and the dose-expansion part of the study.
MLN0128: Participants will receive MLN0128 in the dose-escalation and the dose-expansion part of the study. Receives: Drug: Alisertib; Drug: MLN0128 |
| Dose Level 2: Alisertib 30mg/MLNO128 2 mg | Experimental | This group will receive a Dose-Escalation: Combination of MLN0128 and Alisertib using a standard 3 + 3 design. The starting dose of Alisertib is 30 mg given PO twice daily (BID) Days 1-7 repeat every 21 days. The starting dose for MLN0128 is 2 mg given by mouth (PO) once daily with continuous dosing.
Alisertib: Participants will receive Alisertib in the dose-escalation and the dose-expansion part of the study. Receives: Drug: Alisertib; Drug: MLN0128 |
| Dose Level 3: Alisertib 40 mg/MLNO128 2 mg | Experimental | This group will receive a Dose-Escalation: Combination of MLN0128 and Alisertib using a standard 3 + 3 design. The starting dose of Alisertib is 40 mg given PO twice daily (BID) Days 1-7 repeat every 21 days. The starting dose for MLN0128 is 1 mg given by mouth (PO) once daily with continuous dosing.
Alisertib: Participants will receive Alisertib in the dose-escalation and the dose-expansion part of the study. Receives: Drug: Alisertib; Drug: MLN0128 |
| Dose Level 4: Alisertib 40 mg/MLN0128 3 mg | Experimental | This group will receive a Dose-Escalation: Combination of MLN0128 and Alisertib using a standard 3 + 3 design. The starting dose of Alisertib is 40 mg given PO twice daily (BID) Days 1-7 repeat every 21 days. The starting dose for MLN0128 is 3 mg given by mouth (PO) once daily with continuous dosing.
Alisertib: Participants will receive Alisertib in the dose-escalation and the dose-expansion part of the study. Receives: Drug: Alisertib; Drug: MLN0128 |
| Dose-Expansion of Alisertib and Dose-Expansion of MLN0128: Group 1 | Experimental | This group will receive a Dose-Expansion of Alisertib and Dose-Expansion of MLN0128. In cycle 1, single agent Alisertib will be administered at the MTD on days 1-7 and MLN0128 will be administered on days 8-21. In cycle 2 and beyond, dosing with both agents will begin on day 1, with Alisertib administered days 1-7 and MLN0128 administered days 1-21.
Pancreatic Cancer Cohort:
This group will receive a Dose-Expansion of Alisertib and Dose-Expansion of MLN0128. On each cycle, Alisertib will be administered on days 1-7, while MLN0128 will be administered continuously on days 1-21. Receives: Drug: Alisertib; Drug: MLN0128 |
| Dose-Expansion of Alisertib and Dose-Expansion of MLN0128: Group 2 | Experimental | This group will receive a Dose-Expansion of Alisertib and Dose-Expansion of MLN0128. In cycle 1, MLN0128 will be administered at the MTD days 1-28 and Alisertib will be administered at the MTD on days 8-15. In cycle 2 and beyond, dosing with both agents will begin on day 1, with Alisertib administered days 1-7 and MLN0128 administered days 1-21. Receives: Drug: Alisertib; Drug: MLN0128 |
| Pancreatic Cohort | Experimental | This group will receive a Dose-Expansion of Alisertib and Dose-Expansion of MLN0128. On each cycle, Alisertib will be administered on days 1-7, while MLN0128 will be administered continuously on days 1-21. Receives: Drug: Alisertib; Drug: MLN0128 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Maximum Tolerated Dose (MTD) in the Combination of MLN0128 and Alisertib in Patients With Advanced Solid Tumors Measured by Treatment Adverse Events as Assessed by the CTCAE v4.03
The maximum tolerated dose (MTD) will be defined as the highest dose level evaluated in which 0 or 1 patient out of 6 patients experiences dose limiting toxicity (DLT) in the combination of MLN0128 and Alisertib. Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03.
Measured: Up to 28 days
Secondary outcomes (1)
The Safety Profile and Tolerability of the Combination of MLN0128 and Alisertib in Adult Patients With Advanced Solid Tumors.
Adverse events will be tabulated by type and grade according to the NCI CTCAE v.4.03. Please see adverse events section.
Measured: At least 30 days after the last dose of MLN0128 or alisertib
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2016 (estimated)
- Study start13 May 2016
- Primary completion18 Mar 2020
- Study completion18 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jennifer R. Diamond, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02719691
- Sponsor's protocol ID
- 15-1135.cc
- Status last verified
- May 2022
- First submitted
- 21 Mar 2016
- Last updated
- 25 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Study of the Combination of MLN0128 (Dual TORC1/2 Inhibitor) and MLN8237 (Aurora A Inhibitor, Alisertib) in Patients With Advanced Solid Tumors With an Expansion Cohort in Metastatic Triple-negative Breast Cancer (TNBC)
- ClinicalTrials.gov ID
- NCT02719691
- Acronym / sponsor ID
- 15-1135.cc
- Conditions
- Metastatic Breast Cancer, Solid Tumors
- Keywords
- MLN0128, Dual TORC1/2 Inhibitor, MLN8237, Aurora A inhibitor, Alisertib, Triple-Negative Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- 13 May 2016 (actual)
- Primary completion
- 18 Mar 2020 (actual)
- Study completion
- 18 Mar 2020 (actual)
- First posted
- 25 Mar 2016 (estimated)
- Results
- Posted 19 Jan 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase Ib study designed to evaluate the safety and toxicity of the combination of Alisertib and MLN0128 in patients with advanced solid tumors with an expansion cohort in patients with previously treated metastatic TNBC.
Detailed description
The purpose of this study is to evaluate the combination of Alisertib and MLN0128 in patients with advanced solid tumors refractory to standard treatment followed by an expansion cohort of patients with metastatic TNBC with exploratory correlative studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Dose level 1: Alisertib 30mg/MLNO128 1mg | Experimental | Drug: Alisertib, Drug: MLN0128This group will receive a Dose-Escalation: Combination of MLN0128 and Alisertib using a standard 3 + 3 design. The starting dose of Alisertib is 30 mg given PO twice daily (BID) Days 1-7 repeat every 21 days. The starting dose for MLN0128 is 1 mg given by mouth (PO) once daily with continuous dosing. Alisertib: Participants will receive Alisertib in the dose-escalation and the dose-expansion part of the study. MLN0128: Participants will receive MLN0128 in the dose-escalation and the dose-expansion part of the study. |
| Dose Level 2: Alisertib 30mg/MLNO128 2 mg | Experimental | Drug: Alisertib, Drug: MLN0128This group will receive a Dose-Escalation: Combination of MLN0128 and Alisertib using a standard 3 + 3 design. The starting dose of Alisertib is 30 mg given PO twice daily (BID) Days 1-7 repeat every 21 days. The starting dose for MLN0128 is 2 mg given by mouth (PO) once daily with continuous dosing. Alisertib: Participants will receive Alisertib in the dose-escalation and the dose-expansion part of the study. |
| Dose Level 3: Alisertib 40 mg/MLNO128 2 mg | Experimental | Drug: Alisertib, Drug: MLN0128This group will receive a Dose-Escalation: Combination of MLN0128 and Alisertib using a standard 3 + 3 design. The starting dose of Alisertib is 40 mg given PO twice daily (BID) Days 1-7 repeat every 21 days. The starting dose for MLN0128 is 1 mg given by mouth (PO) once daily with continuous dosing. Alisertib: Participants will receive Alisertib in the dose-escalation and the dose-expansion part of the study. |
| Dose Level 4: Alisertib 40 mg/MLN0128 3 mg | Experimental | Drug: Alisertib, Drug: MLN0128This group will receive a Dose-Escalation: Combination of MLN0128 and Alisertib using a standard 3 + 3 design. The starting dose of Alisertib is 40 mg given PO twice daily (BID) Days 1-7 repeat every 21 days. The starting dose for MLN0128 is 3 mg given by mouth (PO) once daily with continuous dosing. Alisertib: Participants will receive Alisertib in the dose-escalation and the dose-expansion part of the study. |
| Dose-Expansion of Alisertib and Dose-Expansion of MLN0128: Group 1 | Experimental | Drug: Alisertib, Drug: MLN0128This group will receive a Dose-Expansion of Alisertib and Dose-Expansion of MLN0128. In cycle 1, single agent Alisertib will be administered at the MTD on days 1-7 and MLN0128 will be administered on days 8-21. In cycle 2 and beyond, dosing with both agents will begin on day 1, with Alisertib administered days 1-7 and MLN0128 administered days 1-21. Pancreatic Cancer Cohort: This group will receive a Dose-Expansion of Alisertib and Dose-Expansion of MLN0128. On each cycle, Alisertib will be administered on days 1-7, while MLN0128 will be administered continuously on days 1-21. |
| Dose-Expansion of Alisertib and Dose-Expansion of MLN0128: Group 2 | Experimental | Drug: Alisertib, Drug: MLN0128This group will receive a Dose-Expansion of Alisertib and Dose-Expansion of MLN0128. In cycle 1, MLN0128 will be administered at the MTD days 1-28 and Alisertib will be administered at the MTD on days 8-15. In cycle 2 and beyond, dosing with both agents will begin on day 1, with Alisertib administered days 1-7 and MLN0128 administered days 1-21. |
| Pancreatic Cohort | Experimental | Drug: Alisertib, Drug: MLN0128This group will receive a Dose-Expansion of Alisertib and Dose-Expansion of MLN0128. On each cycle, Alisertib will be administered on days 1-7, while MLN0128 will be administered continuously on days 1-21. |
Who may qualify
- Ages
- 18 to 101 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (33 listed)
- Each patient must meet all of the following inclusion criteria to be enrolled in the study:
- Male or female patients 18 years or older.
- Dose Escalation Cohort: Patients must have a diagnosis of a histologically confirmed solid tumor that is incurable and refractory to standard therapy or for which no standard therapy exists.
- Dose Expansion Cohort Group 1 and 2: Patients must have a diagnosis of histologically confirmed metastatic TNBC defined as negative for estrogen receptor, progesterone receptor and HER2. Patients must have received either adjuvant or first line chemotherapy for metastatic disease. Negative for Estrogen and Progesterone Receptor includes the following:
- Pancreatic Cancer Cohort: Patients must have a diagnosis of locally advanced or metastatic pancreatic adenocarcinoma previously treated with or not a candidate for standard of care systemic therapy. Dose Expansion Cohort Group 1 and 2: At least one tumor lesion amenable to repeat core needle biopsy or punch biopsy without unacceptable risk of a major procedural complication.
Key exclusion criteria (31 listed)
- Patients meeting any of the following exclusion criteria are not to be enrolled in the study:
- Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise the patient's participation in the study.
- Known human immunodeficiency virus infection.
- Radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is considered to be over 25%.
- Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlisertibAlso: Dual TORC1/2 InhibitorParticipants will receive Alisertib in the dose-escalation and the dose-expansion part of the study. | Drug | Dose Level 2: Alisertib 30mg/MLNO128 2 mg, Dose Level 3: Alisertib 40 mg/MLNO128 2 mg, Dose Level 4: Alisertib 40 mg/MLN0128 3 mg, Dose level 1: Alisertib 30mg/MLNO128 1mg, Dose-Expansion of Alisertib and Dose-Expansion of MLN0128: Group 1, Dose-Expansion of Alisertib and Dose-Expansion of MLN0128: Group 2, Pancreatic Cohort |
| MLN0128Also: MLN8237 (Aurora A inhibitor)Participants will receive MLN0128 in the dose-escalation and the dose-expansion part of the study. | Drug | Dose Level 2: Alisertib 30mg/MLNO128 2 mg, Dose Level 3: Alisertib 40 mg/MLNO128 2 mg, Dose Level 4: Alisertib 40 mg/MLN0128 3 mg, Dose level 1: Alisertib 30mg/MLNO128 1mg, Dose-Expansion of Alisertib and Dose-Expansion of MLN0128: Group 1, Dose-Expansion of Alisertib and Dose-Expansion of MLN0128: Group 2, Pancreatic Cohort |
Primary outcome
The Maximum Tolerated Dose (MTD) in the Combination of MLN0128 and Alisertib in Patients With Advanced Solid Tumors Measured by Treatment Adverse Events as Assessed by the CTCAE v4.03
Time frame: Up to 28 days
The maximum tolerated dose (MTD) will be defined as the highest dose level evaluated in which 0 or 1 patient out of 6 patients experiences dose limiting toxicity (DLT) in the combination of MLN0128 and Alisertib. Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03.
1 secondary outcome
The Safety Profile and Tolerability of the Combination of MLN0128 and Alisertib in Adult Patients With Advanced Solid Tumors.
Time frame: At least 30 days after the last dose of MLN0128 or alisertib
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jennifer R. Diamond, MD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Alisertib and MLN0128 in people with Metastatic Breast Cancer and Solid Tumors, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 33 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Maximum Tolerated Dose (MTD) in the Combination of MLN0128 and Alisertib in Patients With Advanced Solid Tumors Measured by Treatment Adverse Events as Assessed by the CTCAE v4.03 (time frame: Up to 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2022.