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Non-small Cell Lung Cancer MetastaticPhase 1/2NCT01471964

Study to Assess Safety and Tolerability of MLN8237, In Combination With Erlotinib to Treat Non-Small Cell Lung Cancer

A Phase 1/2 study testing MLN8237 and Erlotinib in people with Non-small Cell Lung Cancer Metastatic and Non-small Cell Lung Cancer Recurrent, run by Fox Chase Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase I/II trial studies the side effects and the best dose of MLN8237 when given together with erlotinib hydrochloride and to see how well it works in treating patients with recurrent locally advanced or metastatic non-small cell lung cancer (NSCLC). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
MLN8237 and Erlotinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
1 siteUnited States
Study dates
20 Oct 2011to 10 Apr 2018
Phase
Phase 1/2
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

  • Patients with cytologically or histologically confirmed recurrent locally advanced or metastatic NSCLC have received at least one prior recognized systemic therapy for therapy for advanced disease, (recognized therapy must include a platinum doublet unless contraindicated due to organ dysfunction)
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
  • Measurable disease by Response Evaluation Criteria in Solid Tumors- (RECIST) 1.1 criteria; previous irradiated tumor is acceptable if there is at least a 20% increase in the size of the previously irradiated lesion
  • Absolute neutrophil count (ANC) >= 1500/mm^3
  • Platelets >= 100,000/mm^3
  • Hemoglobin (Hgb) >= 9g/dL
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  • Total bilirubin =< upper limit of normal (ULN)
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamic pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 1.5 x ULN; AST and/or ALT may be up to 5 X ULN if with known liver mets
  • Adequate renal function as defined by: calculated creatinine clearance must be at least 40 mL/minute (Cockcroft-Gault)
  • Serious, active infections must be controlled; patients may be enrolled while still on antibiotics as long as clinical signs of active infection are absent
  • Previous radiation allowed provided the patient has recovered from the acute and chronic side effects to =< grade 1 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events v. 4.0 [CTCAE v 4.0])
  • Availability of archival diagnostic tissue (paraffin tissue block of resected tumor, core biopsy, fine needle aspirate cell block, or if block cannot be submitted 20-25 [5 micron] unstained slides cut from a block representative of tumor, is required)
  • Able and willing to sign an informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization
  • Able and willing to swallow and absorb orally administered medications and maintain a fast as required before and after MLN8237 administration
  • Women of childbearing potential (WOCBP) and men who are sexually active, even if surgically sterilized, with WOCBP must agree to use effective methods of contraception during active treatment, for the duration of the study, and for 3 months after the completion of the study

Who cannot join

  • Prior treatment with an investigational or marketed inhibitor of the epidermal growth factor receptor (EGFR) pathway or an Aurora Kinase inhibitor
  • Patients with mutations in the EGFR gene; the mutational status of all patients will be determined prior to study entry
  • Prior malignancy within the past 3 years other than complete resection of basal or squamous cell carcinoma of the skin, any in situ malignancy, or low-risk prostate cancer after curative therapy
  • Prior systemic therapy within 14 days of initiating protocol treatment
  • Radiation therapy to more than 25% of the bone marrow; whole pelvic radiation is considered to be over 25%; (ongoing small field radiation therapy for palliation only is allowed)
  • Treatment 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 and during the study; anticonvulsants at stable doses are allowed
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  • Treatment with Proton Pump Inhibitor (PPI); patients on PPI therapy prior to enrollment must stop using the PPI for at least 4 days prior to the first dose of MLN8237
  • Known central nervous system (CNS) disease, except for treated brain metastasis; treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT]) during the screening period; anticonvulsants (stable doses) are allowed; treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, linear accelerator [LINAC], or equivalent) or a combination as deemed appropriate by the treating physician; patients with CNS metastases treated by neurosurgical resection or brain biopsy performed < 4 weeks prior to Day 1 will be excluded
  • Uncontrolled or unstable medical or psychiatric co-morbidities which would clearly preclude use of MLN8237 or erlotinib
  • Current, recent (within 2 weeks of enrollment of this study), or planned participation in an experimental drug study
  • Unstable angina
  • New York Heart Association (NYHA) Grade III or greater congestive heart failure
  • History of myocardial infarction within 6 months of enrollment
  • Abnormal electrocardiogram (EKG): severe uncontrolled ventricular arrhythmias, or evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any EKG abnormality at screening has to be documented by the investigator as not medically relevant
  • Pregnant (positive serum pregnancy test) or breast feeding
  • History of any disease that could lead to impaired absorption of drugs
  • Known hypersensitivity to any component of the trial agents
  • Inability to comply with study and/or follow-up procedures
  • Prior allogeneic bone marrow or organ transplantation
  • Patient has >= grade 2 (CTCAE v 4.0) peripheral neuropathy within 14 days before enrollment
  • Known history of uncontrolled sleep apnea syndrome and other conditions according to enrolling investigator that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen therapy; or requirement of recurrent thoracentesis to manage pleural effusions
  • Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C; testing is not required in the absence of clinical findings or suspicion

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

Other trials in United States

About this study

Official title: A Phase I/II Trial to Assess Safety and Tolerability of an Oral Aurora Kinase A Inhibitor, MLN8237, In Combination With Erlotinib In Patients With Recurrent or Metastatic Non-Small Cell Lung Cancer

This phase I/II trial studies the side effects and the best dose of MLN8237 when given together with erlotinib hydrochloride and to see how well it works in treating patients with recurrent locally advanced or metastatic non-small cell lung cancer (NSCLC). MLN8237 and erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Safety and tolerability of the combination treatment. (Phase I) II. Maximum tolerated dose (MTD) of MLN8237 (alisertib) when given in combination with standard dose erlotinib (erlotinib hydrochloride). (Phase I) III. Progression free survival. (Phase II)

SECONDARY OBJECTIVES:

  1. Pharmacokinetic (PK) parameters of erlotinib and MLN8237, including, but not limited to maximum concentration of drug (Cmax), time of occurrence for maximum drug concentration (Tmax), and area under the curve from time zero to the last measurable concentration(AUC0-t last).

II. Overall response rate (ORR), duration of response (DOR), time to progression (TTP), and overall survival (OS). (Phase II) III. Adverse events (AEs), serious adverse events (SAEs), assessments of clinical laboratory values. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of alisertib followed by a phase II study.

Patients receive alisertib orally (PO) twice daily (BID) on days 1-7 and erlotinib hydrochloride PO once daily (QD) on days 1-21. Courses repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

Being tested
MLN8237 and Erlotinib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MLN8237 and ErlotinibDrug

    Also called MLN8237 Aurora A kinase inhibitor, alisertib, Erlotinib, CP-358,774, erlotinib hydrochloride, Tarceva, OSI-774

    Erlotinib pills once every day and MLN8237 pills twice every day, day 1-7 of every 21 days

Study groups in NCT01471964
Study groupRoleWhat they receive
MLN8237 and ErlotinibExperimentalPhase I Erlotinib 100 mg PO daily* + MLN8237 30 mg PO BID (days 1 - 7), escalating to Erlotinib 150mg PO daily + MLN8237 starting at 30mg PO BID days 1-7, escalating to 40mg BID (days 1 - 7) , then 50mg BID (days 1 - 7). Phase II Erlotinib 150mg PO daily + MLN8237 at MTD from phase I.
Receives: Drug: MLN8237 and Erlotinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and tolerability of the combination treatment (Phase I)

    Toxicity will be evaluated according to the NCI CTCAE, version 4.0.

    Measured: Participants will be followed for the duration of treatment (up to 2 years) through 30 days of completion of treatment

  2. MTD of alisertib when given in combination with standard dose erlotinib hydrochloride (Phase I)

    MTD is the highest dose tried for which there were either 0 or at most 1 dose-limiting toxicity (DLT) in 6 patients. Any dose that leads to 2 DLTs will be considered too toxic and no additional patients will be treated at that level. Although DLTs may occur at any point during treatment, only DLTs occurring during course 1 of treatment during the Phase 1 portion of this study will necessarily influence decisions regarding dose escalation, expansion of a dose level, or evaluation of intermediate dose levels.

    Measured: Participants will be followed for the duration of treatment (up to 2 years)

  3. PFS (Phase II)

    PFS and OS will be treated by the method of Kaplan and Meier. The Phase II component will follow a two stage design that allows for early termination of the study if the primary end point of PFS is not met. The phase II part will use an early stopping design 36 that evaluates patients at 9 weeks and again at 18 weeks. Patients still progression free at 9 weeks will remain on study until progression or the end of their follow up period.

    Measured: Participants will be followed for the duration of treatment (up to 2 years) until the date of first documented progression or date of death for any cause, whichever came first

Secondary outcomes (6)

  1. PK parameters of erlotinib hydrochloride and alisertib, including, but not limited to Cmax, Tmax, and AUC 0-tlast

    Measured: Day 7 and day 21 (optional) of course 1

  2. ORR (Phase II)

    RECIST v1.1 criteria will be used for objective tumor response assessment. Assessments will be performed after every three cycles of treatments (every 9 weeks). Once protocol treatment has been completed subjects will be assessed every three months or sooner as indicated and judged by treating physicians.

    Measured: Participants will be followed for the duration of treatment (up to 2 years) until the date of first documented progression or date of death for any cause, whichever came first

  3. DOR (Phase II)

    The duration of overall response is measured from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

    Measured: Participants will be followed for the duration of treatment (up to 2 years) until the date of first documented progression or date of death for any cause, whichever came first

  4. TTP (Phase II)

    Measured: Participants will be followed for the duration of treatment (up to 2 years) until the date of first documented progression or date of death for any cause, whichever came first

  5. OS (Phase II)

    PFS and OS will be treated by the method of Kaplan and Meier.

    Measured: Participants will be followed for the duration of treatment (up to 2 years) until the date of first documented progression or date of death for any cause, whichever came first

  6. AEs, SAEs, and assessments of clinical laboratory values (Phase II)

    AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a medical treatment or procedure regardless of whether it is considered related to the medical treatment or procedure. Attributable AE, with CTCAE v4 grading should be monitored and recorded until resolved to =< grade I or determined to be irreversible.

    Measured: Participants will be followed for the duration of treatment (up to 2 years) through 30 days of completion of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Nov 2011 (estimated)
  2. Study start20 Oct 2011
  3. Primary completion7 Feb 2017
  4. Study completion10 Apr 2018

Why it stopped: Phase I portion completed. Phase II will open pending amendment approval.

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01471964
Sponsor's protocol ID
OER-TH-036
Other IDs
NCI-2011-03306
Status last verified
May 2018
First submitted
4 Nov 2011
Last updated
17 May 2018
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing MLN8237 and Erlotinib in people with Non-small Cell Lung Cancer Metastatic and Non-small Cell Lung Cancer Recurrent, run by Fox Chase Cancer Center 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 15 inclusion and 22 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 17 May 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 was stopped early (reason given: Phase I portion completed. Phase II will open pending amendment approval.). Results are not available in the source record.

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?

Safety and tolerability of the combination treatment (Phase I) (time frame: Participants will be followed for the duration of treatment (up to 2 years) through 30 days of completion of treatment). The study lists 3 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 NCT01471964.

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 17 May 2018.

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