AdenocarcinomaPhase 1NCT01677559
Combining MLN8237 With Nab-Paclitaxel in Patients With Advanced Solid Malignancies
A Phase 1 study testing MLN8237 and nab-Paclitaxel in people with Adenocarcinoma and Pancreatic Neoplasms, run by Washington University School of Medicine at 1 site in United States.
Trial summary
This phase I trial studies the side effects and the best dose of MLN8237 (alisertib) when given together with paclitaxel albumin-stabilized nanoparticle formulation (nab-paclitaxel) in treating patients with solid malignancies that are metastatic or cannot be removed by surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenocarcinoma, Pancreatic Neoplasms
- What is being tested?
- MLN8237 and nab-Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 7 May 2013to 11 Aug 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Patient must have a histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures to not exist or are no longer effective (dose-escalation cohorts only).
- Patient must have a histologically or cytologically confirmed diagnosis of pancreatic cancer or poorly differentiated neuroendocrine tumor and must have been treated with a regimen with known benefit for pancreatic cancer or poorly differentiated neuroendocrine tumor (MTD expansion cohort only).
- Patient must have measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
- Patient must have disease that is easily accessible for a core biopsy as determined by the treating physician or study PI. Patient must agree to the mandatory biopsies at baseline and end of Cycle 2 (MTD expansion cohort only, and at the discretion of the PI/PI optional).
- Patient must be ≥ 18 years of age.
- Patient must have an ECOG performance status of 0 or 1
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- Patient must have normal bone marrow and organ function as defined below:
- Leukocytes ≥ 3,000/mcL
- Absolute neutrophil count ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
- Hemoglobin > 9.0 g/dL
- Total bilirubin ≤ institutional ULN
- AST and ALT < 1.5 x ULN (or < 5 x ULN if known liver metastases)
- Calculated creatinine clearance must be > 40 mL/min (by Cockcroft-Gault)
- If a female of childbearing potential (defined as a female who is non-menopausal or surgically sterilized), patient must be willing to use an acceptable method of birth control (i.e., hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. If a male with a partner who is a female of childbearing potential, patient must agree to use an acceptable method of contraception during the entire study treatment period through 4 months after the last dose of MLN8237. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- Patient must be able to take oral medication and to maintain a fast as required for 2 hours before and 1 hour after MLN8237 administration.
- Patient (or legally authorized representative if applicable) must be able to understand and willing to sign an IRB approved written informed consent document.
- Both men and women and members of all races and ethnic groups are eligible for this trial.
Who cannot join
- Patient must not have received chemotherapy or radiotherapy ≤ 4 weeks or 5 half-lives prior to study entry.
- Patient must not have had radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is considered to be over 25%.
- Patient must not have a history of other malignancy ≤ 2 years previous with the exception of basal cell or squamous cell carcinoma of the skin which was treated with local resection only, an in situ malignancy, or low-risk prostate cancer after curative therapy.
- Patient must not have had a prior allogeneic bone marrow or organ transplantation.
- Patient must not have previously received nab-paclitaxel.
- Patient must not have received any other investigational agents within 14 days prior to study enrollment.
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- Patient must not have known brain metastases. Patients with known brain metastases must be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- Patient must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to either MLN8237 or nab-paclitaxel, or other agents used in the study.
- Patient must not have been treated with clinically significant enzyme inducers, such as the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine, or Phenobarbital, or rifampin, rifabutin, rifapentine, or St. John's wort within 14 days prior to the first dose of MLN8237.
- Patient must not have received any previous treatment with any Aurora-kinase inhibitors (MTD expansion cohort only).
- Patient must not have a history of gastric resection (MTD expansion cohort only).
- Patient must not have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled diabetes, malabsorption, resection of the pancreas or upper small bowel, symptomatic congestive heart failure, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patient must not have ≥ grade 2 peripheral neuropathy within 14 days before enrollment.
- Patient must not have a known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease.
- Patient must not have a requirement for supplemental oxygen.
- Patient must not require constant administration of a proton pump inhibitor, H2 antagonist, or pancreatic enzymes. Intermittent uses of antacids or H2 antagonists are allowed.
- Patient must not have QTc > 500ms within 14 days before enrollment.
- Patient must not have had a myocardial infarction within 6 months prior to enrollment or have New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
- Patient must not be pregnant and/or breastfeeding.
- Patient must not be known to be HIV-positive on combination antiretroviral because of the potential for pharmacokinetic interactions with MLN8237 or Abraxane. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Phase I Study Combining MLN8237 With Nab-Paclitaxel in Patients With Advanced Solid Malignancies
This phase I trial studies the side effects and the best dose of MLN8237 (alisertib) when given together with paclitaxel albumin-stabilized nanoparticle formulation (nab-paclitaxel) in treating patients with solid malignancies that are metastatic or cannot be removed by surgery. Alisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as nab-paclitaxel work by killing the cells or by stopping them from dividing. Giving alisertib together with nab-paclitaxel may provide a more effective anticancer treatment with fewer side effects.
- Conditions
- Adenocarcinoma, Pancreatic Neoplasms
- Being tested
- MLN8237, nab-Paclitaxel
- Medical subject headings
- Adenocarcinoma, Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MLN8237Drug
nab-PaclitaxelDrug
Also called Abraxane, Coroxane, Capxol
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 0 | Experimental | MLN8237 20 mg BID Days 1, 2 and 3 of each week for 3 weeks out of a 4 week cycle.
nab-Paclitaxel 100 mg/m2 IV Day 1 of each week for 3 weeks out of a 4 week cycle. Receives: Drug: MLN8237; Drug: nab-Paclitaxel |
| Dose Level 1 | Experimental | MLN8237 30 mg BID Days 1, 2 and 3 of each week for 3 weeks out of a 4 week cycle.
nab-Paclitaxel 100 mg/m2 IV Day 1 of each week for 3 weeks out of a 4 week cycle. Receives: Drug: MLN8237; Drug: nab-Paclitaxel |
| Dose Level 2 | Experimental | MLN8237 40 mg BID Days 1, 2 and 3 of each week for 3 weeks out of a 4 week cycle.
nab-Paclitaxel 100 mg/m2 IV Day 1 of each week for 3 weeks out of a 4 week cycle. Receives: Drug: MLN8237; Drug: nab-Paclitaxel |
| Dose Level 3 | Experimental | MLN8237 50 mg BID Days 1, 2 and 3 of each week for 3 weeks out of a 4 week cycle.
nab-Paclitaxel 100 mg/m2 IV Day 1 of each week for 3 weeks out of a 4 week cycle. Receives: Drug: MLN8237; Drug: nab-Paclitaxel |
| MTD Expansion Phase | Experimental | MLN8237 as determined during the dose escalation phase on Days 1, 2 and 3 of each week for 3 weeks out of a 4 week cycle.
nab-Paclitaxel 100 mg/m2 IV Day 1 of each week for 3 weeks out of a 4 week cycle. Receives: Drug: MLN8237; Drug: nab-Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD)
Measured: Completion of cycle 1
Dose-limiting toxicities (DLTs)
Hematologic DLT is defined as any of the following that occurs during the first cycle that is attributed as possibly, probably or definitely related to the study treatment:
- Grade 4 neutropenia > 7 days duration
- Febrile neutropenia of any duration with temperature ≥ 38.5 °C
- Grade 4 thrombocytopenia > 7 days duration
Non-hematologic DLT is defined as any possibly, probably, or definitely related grade 3 or grade 4 non-hematologic toxicity that occurs during the first cycle with the following specific exceptions:
- Grade 3 fatigue
- Grade 3 or 4 nausea, vomiting, or anorexia that returns to Grade 1 prior to the start of Cycle 2
- Grade 3 non-hematological laboratory abnormalities that resolve to grade 1 or baseline prior to the start of Cycle 2
Any delay in treatment >14 days that is possibly, probably, or definitely related to study treatment will be considered a DLT.
Measured: Completion of cycle 1
Secondary outcomes (1)
Antitumor activity of MLN8237 and nab-paclitaxel combination therapy
Overall response rate (ORR = CR + PR) as a preliminary measure
Measured: 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2012 (estimated)
- Study start7 May 2013
- Primary completion30 Sep 2014
- Study completion11 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andrea Wang-Gillam, M.D., Ph.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01677559
- Sponsor's protocol ID
- 201210123
- Status last verified
- Jan 2018
- First submitted
- 27 Aug 2012
- Last updated
- 11 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lim KH, Opyrchal M, Acharya A, Boice N, Wu N, Gao F, Webster J, Lockhart AC, Waqar SN, Govindan R, Morgensztern D, Picus J, Tan BR, Baggstrom MQ, Maher CA, Wang-Gillam A. Phase 1 study combining alisertib with nab-paclitaxel in patients with advanced solid malignancies. Eur J Cancer. 2021 Sep;154:102-110. doi: 10.1016/j.ejca.2021.06.012. Epub 2021 Jul 10.
PubMed 34256279
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study Combining MLN8237 With Nab-Paclitaxel in Patients With Advanced Solid Malignancies
- ClinicalTrials.gov ID
- NCT01677559
- Acronym / sponsor ID
- 201210123
- Conditions
- Adenocarcinoma, Pancreatic Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 7 May 2013 (actual)
- Primary completion
- 30 Sep 2014 (actual)
- Study completion
- 11 Aug 2017 (actual)
- First posted
- 3 Sep 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial studies the side effects and the best dose of MLN8237 (alisertib) when given together with paclitaxel albumin-stabilized nanoparticle formulation (nab-paclitaxel) in treating patients with solid malignancies that are metastatic or cannot be removed by surgery. Alisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as nab-paclitaxel work by killing the cells or by stopping them from dividing. Giving alisertib together with nab-paclitaxel may provide a more effective anticancer treatment with fewer side effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Dose Level 0 | Experimental | Drug: MLN8237, Drug: nab-PaclitaxelMLN8237 20 mg BID Days 1, 2 and 3 of each week for 3 weeks out of a 4 week cycle. nab-Paclitaxel 100 mg/m2 IV Day 1 of each week for 3 weeks out of a 4 week cycle. |
| Dose Level 1 | Experimental | Drug: MLN8237, Drug: nab-PaclitaxelMLN8237 30 mg BID Days 1, 2 and 3 of each week for 3 weeks out of a 4 week cycle. nab-Paclitaxel 100 mg/m2 IV Day 1 of each week for 3 weeks out of a 4 week cycle. |
| Dose Level 2 | Experimental | Drug: MLN8237, Drug: nab-PaclitaxelMLN8237 40 mg BID Days 1, 2 and 3 of each week for 3 weeks out of a 4 week cycle. nab-Paclitaxel 100 mg/m2 IV Day 1 of each week for 3 weeks out of a 4 week cycle. |
| Dose Level 3 | Experimental | Drug: MLN8237, Drug: nab-PaclitaxelMLN8237 50 mg BID Days 1, 2 and 3 of each week for 3 weeks out of a 4 week cycle. nab-Paclitaxel 100 mg/m2 IV Day 1 of each week for 3 weeks out of a 4 week cycle. |
| MTD Expansion Phase | Experimental | Drug: MLN8237, Drug: nab-PaclitaxelMLN8237 as determined during the dose escalation phase on Days 1, 2 and 3 of each week for 3 weeks out of a 4 week cycle. nab-Paclitaxel 100 mg/m2 IV Day 1 of each week for 3 weeks out of a 4 week cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patient must have a histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures to not exist or are no longer effective (dose-escalation cohorts only).
- Patient must have a histologically or cytologically confirmed diagnosis of pancreatic cancer or poorly differentiated neuroendocrine tumor and must have been treated with a regimen with known benefit for pancreatic cancer or poorly differentiated neuroendocrine tumor (MTD expansion cohort only).
- Patient must have measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
- Patient must have disease that is easily accessible for a core biopsy as determined by the treating physician or study PI. Patient must agree to the mandatory biopsies at baseline and end of Cycle 2 (MTD expansion cohort only, and at the discretion of the PI/PI optional).
- Patient must be ≥ 18 years of age.
Key exclusion criteria (20 listed)
- Patient must not have received chemotherapy or radiotherapy ≤ 4 weeks or 5 half-lives prior to study entry.
- Patient must not have had radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is considered to be over 25%.
- Patient must not have a history of other malignancy ≤ 2 years previous with the exception of basal cell or squamous cell carcinoma of the skin which was treated with local resection only, an in situ malignancy, or low-risk prostate cancer after curative therapy.
- Patient must not have had a prior allogeneic bone marrow or organ transplantation.
- Patient must not have previously received nab-paclitaxel.
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 |
|---|---|---|
| MLN8237 | Drug | Dose Level 0, Dose Level 1, Dose Level 2, Dose Level 3, MTD Expansion Phase |
| nab-PaclitaxelAlso: Abraxane, Coroxane, Capxol | Drug | Dose Level 0, Dose Level 1, Dose Level 2, Dose Level 3, MTD Expansion Phase |
Primary outcome
Maximum tolerated dose (MTD)
Time frame: Completion of cycle 1
Dose-limiting toxicities (DLTs)
Time frame: Completion of cycle 1
Hematologic DLT is defined as any of the following that occurs during the first cycle that is attributed as possibly, probably or definitely related to the study treatment: * Grade 4 neutropenia > 7 days duration * Febrile neutropenia of any duration with temperature ≥ 38.5 °C * Grade 4 thrombocytopenia > 7 days duration Non-hematologic DLT is defined as any possibly, probably, or definitely related grade 3 or grade 4 non-hematologic toxicity that occurs during the first cycle with the following specific exceptions: * Grade 3 fatigue * Grade 3 or 4 nausea, vomiting, or anorexia that returns to Grade 1 prior to the start of Cycle 2 * Grade 3 non-hematological laboratory abnormalities that resolve to grade 1 or baseline prior to the start of Cycle 2 Any delay in treatment >14 days that is possibly, probably, or definitely related to study treatment will be considered a DLT.
1 secondary outcome
Antitumor activity of MLN8237 and nab-paclitaxel combination therapy
Time frame: 60 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2018.
- Derived from this study: PubMed 34256279Lim KH, Opyrchal M, Acharya A, Boice N, Wu N, Gao F, Webster J, Lockhart AC, Waqar SN, Govindan R, Morgensztern D, Picus J, Tan BR, Baggstrom MQ, Maher CA, Wang-Gillam A. Phase 1 study combining alisertib with nab-paclitaxel in patients with advanced solid malignancies. Eur J Cancer. 2021 Sep;154:102-110. doi: 10.1016/j.ejca.2021.06.012. Epub 2021 Jul 10.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- 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.
Andrea Wang-Gillam, M.D., Ph.D. principal investigator
Washington University School of Medicine
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 MLN8237 and nab-Paclitaxel in people with Adenocarcinoma and Pancreatic Neoplasms, run by Washington University School of Medicine 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 18 inclusion and 20 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 11 Jan 2018. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum tolerated dose (MTD) (time frame: Completion of cycle 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01677559, which also lists 1 linked publication.
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 11 Jan 2018.