Advanced Solid TumorsPhase 1NCT02367352
Alisertib (MLN8237) in Combination With Weekly Paclitaxel in East Asian Patients With Advanced Solid Tumors
A Phase 1 study testing Alisertib and Paclitaxel in people with Advanced Solid Tumors and Ovarian Cancer, run by Millennium Pharmaceuticals, Inc. at 3 sites in 2 countries.
Trial summary
The purpose of this study is to evaluate the safety and tolerability and determine the MTD to subsequently define an RP2D of alisertib in combination with weekly paclitaxel in East Asian participants with advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors, Ovarian Cancer, Small Cell Lung Cancer
- What is being tested?
- Alisertib and Paclitaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 19 Mar 2015to 23 May 2017
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female participants 18 years or older (or minimum age of legal consent consistent with local regulations) at the time written study informed consent is obtained.
- Participants of East Asian ethnicity (eg, Chinese, Japanese, or Korean).
- Must have a diagnosis of a solid tumor malignancy (escalation part) or relapsed or refractory ovarian cancer (OC) or small cell lung cancer (SCLC) (expansion part).
- Participants in the expansion cohort must have a pathologically (histology or cytology) confirmed diagnosis of either OC (including recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer) or SCLC, which is measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
- Participants in the expansion cohort must not have received more than 2 prior taxane containing regimens.
- No antineoplastic therapy (eg, drugs, biologicals, monoclonal antibodies, etc) or radiotherapy within the 3 weeks before enrollment (14 days for regimens with recovery expected within 7 to 14 days). The participant must have recovered (ie, ≤ Grade 1 toxicity or participant's baseline status, except alopecia) from all treatment-related toxicities.
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- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Adequate bone marrow function as defined by:
- Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 (without need for growth factor support).
- Platelet count ≥ 100,000 cells/mm3 (without need for transfusion or growth factor support).
- Hemoglobin level ≥ 9 g/dL.
- Adequate liver function as defined by:
- Bilirubin < 1.5 times the upper limit of normal (ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN if due to liver metastases)
- Serum albumin equal to or greater than the lower limit of normal
- Adequate renal function as defined by:
- Creatinine clearance ≥ 30 mL/minute (can be calculated using serum creatinine value).
- No more than 2 previous chemotherapy regimen in the metastatic setting.
- Female participants who:
- Are postmenopausal for at least 1 year before the screening visit, OR
- Are 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 30 days after the last dose of study drug
- Adhere to any treatment-specific pregnancy prevention guidelines for paclitaxel
- Male participants, even if surgically sterilized (ie, status postvasectomy), who:
- Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug
- Adhere to any treatment-specific pregnancy prevention guidelines for paclitaxel.
- 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 participant at any time without prejudice to future medical care.
- Suitable venous access for the study-required blood sampling, including pharmacokinetics (PK).
- Ability to swallow tablets.
Who cannot join
- Participants with carcinomatous meningitis.
- Participants with symptomatic and/or progressive brain metastases or treatment with brain edema.
- Known hypersensitivity to Cremophor® EL, paclitaxel, alisertib or their components.
- Prior treatment with an Aurora A specific-targeted or pan-Aurora-targeted agent, including alisertib in any setting.
- Prior history of ≥ Grade 2 neurotoxicity or any toxicity requiring discontinuation from taxane chemotherapy that is not resolved to ≤ Grade 1.
- Participants who received prior weekly taxane-based therapy with early disease progression during or within 1 month of completing therapy (refractory disease).
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- Any comorbid condition or unresolved toxicity that would preclude administration of weekly paclitaxel.
- Systemic treatment with moderate or strong CYP3A inhibitors must be discontinued at least 14 days before the first dose of alisertib, and the use of these agents is not permitted during the study.
- Known gastrointestinal (GI) abnormality (including recurrent nausea or vomiting) or GI procedure that could interfere with or modify the oral intake, absorption, or tolerance of alisertib.
- Participants requiring treatment with clinically significant enzyme inducers, such as the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine, phenobarbital, oxcarbazepine, primidone, rifampin, rifabutin, rifapentine, or St. John's wort within 14 days before the first dose of alisertib or requiring the use of these medications during the study.
- Requirement for administration of proton pump inhibitor (PPI), H2 antagonist (premedication for paclitaxel allowed), or pancreatic enzymes. Use of any PPI in either continued or intermittent use will be prohibited during the conduct of the study and participants must discontinue any use of PPI within 4 days before the first dose of alisertib.
- Life-threatening or severe central nervous system (CNS), pulmonary, renal, or hepatic disease unrelated to cancer, or any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
- Treatment with any investigational products within 5 half-lives before the first dose of study drug.
- Treatment with fully human or chimeric monoclonal antibodies within 42 days before the first dose of study drug (21 days if clear evidence of progression).
- Major surgery within 14 days before the first dose of study drug.
- Infection requiring systemic intravenous (IV) antibiotic therapy within 14 days preceding the first dose of study drug, or other severe infection.
- Known human immunodeficiency virus (HIV) positive.
- Ongoing or active hepatitis B or hepatitis C infection. Testing is not required in the absence of clinical findings or suspicion.
- History of myocardial infarction, unstable symptomatic ischemic heart disease, uncontrolled hypertension despite appropriate medical therapy, any ongoing cardiac arrhythmias of > Grade 2, thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other cardiac condition (eg, pericardial effusion or restrictive cardiomyopathy) within 6 months before receiving the first dose of study drug. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed. Participants with a pacemaker may be enrolled in the study upon discussion with the project clinician.
- Female participants who are in the lactation period or have a positive serum pregnancy test during the Screening period or a positive urine pregnancy test on Day1 before the first dose of study drug.
- Diagnosed with or treated for another malignancy within 3 years before the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type may be enrolled in the study if they have undergone complete resection and no evidence of active disease is present.
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
About this study
Official title: A Phase 1b Study of Alisertib (MLN8237) in Combination With Weekly Paclitaxel in East Asian Patients With Advanced Solid Tumors
The purpose of this study is to evaluate the safety and tolerability and determine the MTD to subsequently define an RP2D of alisertib in combination with weekly paclitaxel in East Asian participants with advanced solid tumors.
Read the detailed description
The drug being tested in this study was called alisertib. Alisertib in combination with paclitaxel was tested to find a safe and well-tolerated dose in East Asian participants. The study consisted of 2 parts: a dose escalation phase to determine the maximum tolerated dose (MTD) and define the recommended phase 2 dose (RP2D) of the alisertib plus paclitaxel combination in East Asian participants with advanced solid tumors; the second part is an expansion cohort at the RP2D of the alisertib plus paclitaxel in East Asian participants with either ovarian cancer or small cell lung cancer. This study looked at safety (lab results and side effects) and pharmacokinetic properties (how the drugs move throughout the body).
This open label study enrolled 9 participants. Dose Escalation Phase: Alisertib tablets at a starting dose of 15 mg, orally, twice daily, 3 days on/4 days off for 3 weeks in 28 day cycle in combination with paclitaxel, 60 mg/m^2 intravenous on days 1, 8, and 15 in 28-day cycles in Cohort 1 escalated to a dose of 25 mg alisertib, orally, twice daily 3 days on/4 days off for 3 weeks in 28 day cycles in Cohort 2. If ≥ 2 participants experience a dose limiting toxicity (DLT) the dose of alisertib decreased to 20 mg. Expansion Cohort: alisertib tablets at the determined RP2D dose orally, twice daily 3 days on/4 days off for 3 weeks in 28 day cycles in combination with paclitaxel, 60 mg/m^2 intravenous. Treatment was continued until disease progression or unacceptable toxicity.
- Alisertib 15 mg to 25 mg tablets
- Paclitaxel 60 mg/m^2 intravenous solution
This multi-centre trial was conducted in Japan and Korea. The overall time to participate in this study was up to 24 months.
The study was terminated early because of the sponsor's decision. Enrollment was completed in the dose escalation cohort, but no participants were enrolled in the dose expansion cohort.
- Being tested
- Alisertib, Paclitaxel
- Keywords
- Drug therapy, Dose escalation, Dose expansion
- Medical subject headings
- Ovarian Neoplasms, Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlisertibDrug
Alisertib tablets
PaclitaxelDrug
Paclitaxel intravenous solution
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 (Dose Escalation Phase) | Experimental | Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles). Receives: Drug: Alisertib; Drug: Paclitaxel |
| Cohort 2 (Dose Escalation Phase) | Experimental | Alisertib 25 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. Dose of alisertib will be de-escalated to 20 mg if ≥ 2 participants experience a dose limiting toxicity (DLT). Receives: Drug: Alisertib; Drug: Paclitaxel |
| Dose Expansion Cohort | Experimental | Alisertib, MTD/RP2D determined in Dose Escalation Phase, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, IV on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. Receives: Drug: Alisertib; Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Escalation Phase: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events.
A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Measured: From Day 1 to 30 days after the last dose of study drug (approximately 21 months)
Dose Escalation Phase: Number of Participants With Clinically Significant Laboratory Findings
The number of participants with any markedly abnormal standard safety laboratory values including serum chemistry, hematology, and urine analysis will be collected throughout study. Laboratory values assessed by the investigator to be clinically significant were reported as adverse events.
Measured: From Day 1 to 30 days after the last dose of study drug (approximately 21 months)
Dose Escalation Phase: Number of Participants With Clinically Significant Vital Sign Findings
The number of participants with any markedly abnormal vital sign values (blood pressure, heart rate, and temperature) will be collected throughout study. Vital signs assessed by the investigator to be clinically significant were reported as adverse events.
Measured: From Day 1 to 30 days after the last dose of study drug (approximately 21 months)
Dose Escalation Phase: Cmax: Maximum Observed Plasma Concentration of Alisertib
Measured: Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose
Dose Escalation Phase: Tmax: Time to Reach the Maximum Plasma Concentration of Alisertib
Measured: Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose
Dose Escalation Phase: AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for Alisertib
Measured: Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose
Dose Escalation Phase: Cmax: Maximum Observed Plasma Concentration of Paclitaxel
Measured: Day 1 predose and Day 1, 2 and 3 at multiple time points (up to 12 hours) post-dose
Dose Escalation Phase: Tmax: Time to Reach the Maximum Plasma Concentration of Paclitaxel
Measured: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Escalation Phase: AUC(0-tlast): Area Under the Plasma Concentration Curve From Time Zero to the Time of the Last Quantifiable Concentration of Paclitaxel
Measured: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Escalation Phase: AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Tme 0 to Infinity
Measured: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Escalation Phase: T½: Terminal Phase Elimination Half-Life of Paclitaxel
Measured: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events.
A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Measured: From Day 1 to 30 days after the last dose of study drug
Dose Expansion Phase: Number of Participants With Clinically Significant Laboratory Findings
The number of participants with any markedly abnormal standard safety laboratory values will be collected throughout study.
Measured: From Day 1 to 30 days after the last dose of study drug
Dose Expansion Phase: Number of Participants With Clinically Significant Vital Sign Findings
The number of participants with any markedly abnormal vital sign values will be collected throughout study.
Measured: From Day 1 to 30 days after the last dose of study drug
Dose Expansion Phase: Cmax: Maximum Observed Plasma Concentration of Alisertib
Measured: Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: Tmax: Time to Reach the Maximum Plasma Concentration of Alisertib
Measured: Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for Alisertib
Measured: Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: Cmax: Maximum Observed Plasma Concentration of Paclitaxel
Measured: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: Tmax: Time to Reach the Maximum Plasma Concentration of Paclitaxel
Measured: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: AUC(0-tlast): Area Under the Plasma Concentration Curve From Time Zero to the Time of the Last Quantifiable Concentration of Paclitaxel
Measured: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of Paclitaxel
Measured: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: T½: Terminal Phase Elimination Half-Life of Paclitaxel
Measured: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Secondary outcomes (1)
Dose Expansion Phase: Overall Response Rate (ORR)
ORR is defined as the percentage of participants with complete response (CR) and partial response (PR) according to disease response based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Measured: Day 21 of every other Cycle beginning with Cycle 2 (Up to 12 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2015 (estimated)
- Study start19 Mar 2015
- Primary completion23 May 2017
- Study completion23 May 2017
Why it stopped: Sponsor's decision
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 Advanced Solid TumorsStudies of the same condition, open and under way.
- 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Millennium Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director Clinical Science, Study director, Millennium Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02367352
- Sponsor's protocol ID
- C14022
- Other IDs
- U1111-1164-7696, JapicCTI-152845
- Status last verified
- Jun 2019
- First submitted
- 11 Feb 2015
- Last updated
- 26 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Study of Alisertib (MLN8237) in Combination With Weekly Paclitaxel in East Asian Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT02367352
- Acronym / sponsor ID
- C14022
- Keywords
- Drug therapy, Dose escalation, Dose expansion
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor's decision
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Millennium Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 19 Mar 2015 (actual)
- Primary completion
- 23 May 2017 (actual)
- Study completion
- 23 May 2017 (actual)
- First posted
- 20 Feb 2015 (estimated)
- Results
- Posted 2 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety and tolerability and determine the MTD to subsequently define an RP2D of alisertib in combination with weekly paclitaxel in East Asian participants with advanced solid tumors.
Detailed description
The drug being tested in this study was called alisertib. Alisertib in combination with paclitaxel was tested to find a safe and well-tolerated dose in East Asian participants. The study consisted of 2 parts: a dose escalation phase to determine the maximum tolerated dose (MTD) and define the recommended phase 2 dose (RP2D) of the alisertib plus paclitaxel combination in East Asian participants with advanced solid tumors; the second part is an expansion cohort at the RP2D of the alisertib plus paclitaxel in East Asian participants with either ovarian cancer or small cell lung cancer. This study looked at safety (lab results and side effects) and pharmacokinetic properties (how the drugs move throughout the body).
This open label study enrolled 9 participants. Dose Escalation Phase: Alisertib tablets at a starting dose of 15 mg, orally, twice daily, 3 days on/4 days off for 3 weeks in 28 day cycle in combination with paclitaxel, 60 mg/m^2 intravenous on days 1, 8, and 15 in 28-day cycles in Cohort 1 escalated to a dose of 25 mg alisertib, orally, twice daily 3 days on/4 days off for 3 weeks in 28 day cycles in Cohort 2. If ≥ 2 participants experience a dose limiting toxicity (DLT) the dose of alisertib decreased to 20 mg. Expansion Cohort: alisertib tablets at the determined RP2D dose orally, twice daily 3 days on/4 days off for 3 weeks in 28 day cycles in combination with paclitaxel, 60 mg/m^2 intravenous. Treatment was continued until disease progression or unacceptable toxicity.
- Alisertib 15 mg to 25 mg tablets
- Paclitaxel 60 mg/m^2 intravenous solution
This multi-centre trial was conducted in Japan and Korea. The overall time to participate in this study was up to 24 months.
The study was terminated early because of the sponsor's decision. Enrollment was completed in the dose escalation cohort, but no participants were enrolled in the dose expansion cohort.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 (Dose Escalation Phase) | Experimental | Drug: Alisertib, Drug: PaclitaxelAlisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles). |
| Cohort 2 (Dose Escalation Phase) | Experimental | Drug: Alisertib, Drug: PaclitaxelAlisertib 25 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. Dose of alisertib will be de-escalated to 20 mg if ≥ 2 participants experience a dose limiting toxicity (DLT). |
| Dose Expansion Cohort | Experimental | Drug: Alisertib, Drug: PaclitaxelAlisertib, MTD/RP2D determined in Dose Escalation Phase, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, IV on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- Male or female participants 18 years or older (or minimum age of legal consent consistent with local regulations) at the time written study informed consent is obtained.
- Participants of East Asian ethnicity (eg, Chinese, Japanese, or Korean).
- Must have a diagnosis of a solid tumor malignancy (escalation part) or relapsed or refractory ovarian cancer (OC) or small cell lung cancer (SCLC) (expansion part).
- No antineoplastic therapy (eg, drugs, biologicals, monoclonal antibodies, etc) or radiotherapy within the 3 weeks before enrollment (14 days for regimens with recovery expected within 7 to 14 days). The participant must have recovered (ie, ≤ Grade 1 toxicity or participant's baseline status, except alopecia) from all treatment-related toxicities.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Key exclusion criteria (21 listed)
- Participants with carcinomatous meningitis.
- Participants with symptomatic and/or progressive brain metastases or treatment with brain edema.
- Known hypersensitivity to Cremophor® EL, paclitaxel, alisertib or their components.
- Prior treatment with an Aurora A specific-targeted or pan-Aurora-targeted agent, including alisertib in any setting.
- Prior history of ≥ Grade 2 neurotoxicity or any toxicity requiring discontinuation from taxane chemotherapy that is not resolved to ≤ Grade 1.
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 |
|---|---|---|
| AlisertibAlisertib tablets | Drug | Cohort 1 (Dose Escalation Phase), Cohort 2 (Dose Escalation Phase), Dose Expansion Cohort |
| PaclitaxelPaclitaxel intravenous solution | Drug | Cohort 1 (Dose Escalation Phase), Cohort 2 (Dose Escalation Phase), Dose Expansion Cohort |
Primary outcome
Dose Escalation Phase: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From Day 1 to 30 days after the last dose of study drug (approximately 21 months)
An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Dose Escalation Phase: Number of Participants With Clinically Significant Laboratory Findings
Time frame: From Day 1 to 30 days after the last dose of study drug (approximately 21 months)
The number of participants with any markedly abnormal standard safety laboratory values including serum chemistry, hematology, and urine analysis will be collected throughout study. Laboratory values assessed by the investigator to be clinically significant were reported as adverse events.
Dose Escalation Phase: Number of Participants With Clinically Significant Vital Sign Findings
Time frame: From Day 1 to 30 days after the last dose of study drug (approximately 21 months)
The number of participants with any markedly abnormal vital sign values (blood pressure, heart rate, and temperature) will be collected throughout study. Vital signs assessed by the investigator to be clinically significant were reported as adverse events.
Dose Escalation Phase: Cmax: Maximum Observed Plasma Concentration of Alisertib
Time frame: Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose
Dose Escalation Phase: Tmax: Time to Reach the Maximum Plasma Concentration of Alisertib
Time frame: Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose
Dose Escalation Phase: AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for Alisertib
Time frame: Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose
Dose Escalation Phase: Cmax: Maximum Observed Plasma Concentration of Paclitaxel
Time frame: Day 1 predose and Day 1, 2 and 3 at multiple time points (up to 12 hours) post-dose
Dose Escalation Phase: Tmax: Time to Reach the Maximum Plasma Concentration of Paclitaxel
Time frame: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Escalation Phase: AUC(0-tlast): Area Under the Plasma Concentration Curve From Time Zero to the Time of the Last Quantifiable Concentration of Paclitaxel
Time frame: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Escalation Phase: AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Tme 0 to Infinity
Time frame: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Escalation Phase: T½: Terminal Phase Elimination Half-Life of Paclitaxel
Time frame: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From Day 1 to 30 days after the last dose of study drug
An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Dose Expansion Phase: Number of Participants With Clinically Significant Laboratory Findings
Time frame: From Day 1 to 30 days after the last dose of study drug
The number of participants with any markedly abnormal standard safety laboratory values will be collected throughout study.
Dose Expansion Phase: Number of Participants With Clinically Significant Vital Sign Findings
Time frame: From Day 1 to 30 days after the last dose of study drug
The number of participants with any markedly abnormal vital sign values will be collected throughout study.
Dose Expansion Phase: Cmax: Maximum Observed Plasma Concentration of Alisertib
Time frame: Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: Tmax: Time to Reach the Maximum Plasma Concentration of Alisertib
Time frame: Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for Alisertib
Time frame: Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: Cmax: Maximum Observed Plasma Concentration of Paclitaxel
Time frame: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: Tmax: Time to Reach the Maximum Plasma Concentration of Paclitaxel
Time frame: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: AUC(0-tlast): Area Under the Plasma Concentration Curve From Time Zero to the Time of the Last Quantifiable Concentration of Paclitaxel
Time frame: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of Paclitaxel
Time frame: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: T½: Terminal Phase Elimination Half-Life of Paclitaxel
Time frame: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
1 secondary outcome
Dose Expansion Phase: Overall Response Rate (ORR)
Time frame: Day 21 of every other Cycle beginning with Cycle 2 (Up to 12 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Medical Director Clinical Science study director
Millennium Pharmaceuticals, Inc.
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Alisertib and Paclitaxel in people with Advanced Solid Tumors and Ovarian Cancer, run by Millennium Pharmaceuticals, Inc. at 3 sites in 2 countries.
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 29 inclusion and 21 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: stopped early, as of the sponsor's last update on 26 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Japan, South Korea. 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 2 May 2019). 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?
Dose Escalation Phase: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: From Day 1 to 30 days after the last dose of study drug (approximately 21 months)). The study lists 22 primary outcomes in all. 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 26 Jun 2019.