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Advanced CancerPhase 1NCT01655225

A Study of LY3023414 in Participants With Advanced Cancer

A Phase 1 study testing LY3023414, Midazolam and Fulvestrant in people with Advanced Cancer and Metastatic Cancer, run by Eli Lilly and Company at 8 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to find a recommended dose level and schedule of dosing LY3023414 that can safely be taken by participants with advanced or metastatic cancer. The study will also explore the changes to various markers in blood cells and potentially tumor cells. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
LY3023414, Midazolam and Fulvestrant
Could I receive a placebo?
No, everyone receives an active treatment
How many people
156 participants
Where
8 sitesin 3 countries
Study dates
31 Jul 2012to 2 Feb 2022
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

  • Parts A, A2 \& B1: Participants must have pathological evidence of a diagnosis of advanced and/or metastatic cancer and must be, in the judgment of the investigator, an appropriate candidate for experimental therapy
  • Part B2: Participants must have advanced, recurrent, or metastatic breast cancer that is refractory to aromatase inhibitors (AI) with either disease recurrence or disease progression; must be hormone receptor positive (HR+) and human epidermal growth factor receptor 2 (HER2)-negative; must be of postmenopausal status or beginning ovarian suppression with a luteinizing hormone-releasing hormone (LHRH) agonist
  • Part B3 only: Participants must have malignant pleural or peritoneal mesothelioma
  • Part B4 only: Participants must have malignant pleural or peritoneal mesothelioma and appropriate candidate for treatment with cisplatin/pemetrexed; no prior systemic chemotherapy
  • Part B5 only: Participants must have histologically confirmed diagnosis of B-cell iNHL, with histological subtype; prior treatment with ≥2 prior chemotherapy- or immunotherapy-based regimens for iNHL
  • Part B6 only: Participants must have squamous NSCLC; documented evidence of an activating molecular aberration of the PI3K/mTOR pathway
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  • Parts B2, B3 \& B6 only: Must have adequate tumor tissue sample from archival biopsy available, or willingness to undergo a fresh tumor biopsy
  • Parts B3, B4, B5 \& B6: No previous treatment with any PI3K and/or mTOR inhibitor
  • Part B7: Must have a diagnosis of HR+ and HER2- breast cancer; have locoregionally recurrent disease not amenable to resection or radiation therapy with curative intent or metastatic disease; no previous treatment or currently receiving 1 of the following treatments for locoregionally recurrent or metastatic breast cancer (chemotherapy, endocrine therapy, CDK4/6 inhibitor, and PI3K and/or mTOR inhibitor)
  • Measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1), modified RECIST or Revised Response Criteria for Malignant Lymphoma
  • Have adequate organ function, including: Absolute neutrophil count (ANC) at least 1.5 x 109/Liter (L), platelets at least 100 x 109/L, and hemoglobin at least 8 grams/deciliter (g/dL); bilirubin no more than 1.5 times upper limits of normal; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) no more than 2.0 times upper limits of normal; Serum creatinine no more than 1.5 times upper limits of normal or calculated creatinine clearance >45 milliliters/minute (mL/min)
  • Have a performance status of at least 1 on the Eastern Cooperative Oncology Group (ECOG) scale and life expectancy >6 months
  • Have discontinued all previous cancer therapies (except nonsteroidal aromatase inhibitors for participants in Part B2), and any agents that have not received regulatory approval for any indication, for at least 21 days or 5 half lives prior to study enrollment, whichever is shorter, and recovered from the acute effects of therapy. Participants must have discontinued mitomycin-C or nitrosourea therapy for at least 42 days
  • Are able to swallow capsules

Who cannot join

  • Have serious preexisting medical conditions
  • Have symptomatic central nervous system (CNS) malignancy (with the exception of medulloblastoma) or metastasis (screening not required).
  • Have known acute or chronic leukemia or current hematologic malignancies (except iNHL for patients in Part B5) that, in the judgment of the investigator and sponsor, may affect the interpretation of results
  • Have an active fungal, bacterial, and/or known viral infection
  • Have a second primary malignancy that in the judgment of the investigator and sponsor may affect the interpretation of results (Part B only)
  • Part B1 only: No concomitant medications that are strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) or midazolam
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  • Intolerance to any previous treatment with any phosphatidylinositol-3-kinase (PI3K) and/or mammalian target of rapamycin (mTOR) inhibitor.
  • Participants with active alcohol abuse, as determined by the investigator
  • Have a history of New York Heart Association (NYHA) Class ≥3, unstable angina, or myocardial infarction (MI) in 6 months prior to study drug administration
  • Have QT corrected interval of >450 milliseconds (msec) on screening electrocardiogram (ECG)
  • Have insulin-dependent diabetes mellitus or a history of gestational diabetes mellitus.
  • Part B only: Hypersensitivity to study drugs given in combination with LY3023414

Trial locations and contacts

8 sites in 3 countries.

8 sites in 3 countries

United States6 sites
  • UCLA Medical Center

    Los Angeles, California, 90095

  • Sarah Cannon Cancer Center

    Nashville, Tennessee, 37203

  • Tennessee Oncology PLLC

    Nashville, Tennessee, 37203

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Peggy and Charles Stephenson Oklahoma Cancer Center

    Oklahoma City, Oklahoma, 73104

  • Penn Presbyterian Medical Center

    Philadelphia, Pennsylvania, 19104

Other trials in United States

Italy1 site
  • Azienda Ospedaliero - Universitaria S. Luigi Gonzaga

    Orbassano, Torino, 10043

Other trials in Italy

Puerto Rico1 site
  • Fundacion de Investigacion de Diego

    San Juan, 00927

Other trials in Puerto Rico

About this study

Official title: A Phase 1 First-in-Human Dose Study of LY3023414 in Patients With Advanced Cancer

The purpose of this study is to find a recommended dose level and schedule of dosing LY3023414 that can safely be taken by participants with advanced or metastatic cancer. The study will also explore the changes to various markers in blood cells and potentially tumor cells. Finally, the study will help document any antitumor activity this drug may have.

In Part A of this study, participants with advanced/metastatic cancer (including lymphoma) will receive increasing doses of LY3023414. In Part B, LY3023414 will be explored in different types of cancer, including breast and lung cancer, lymphoma and mesothelioma.

Being tested
LY3023414, Midazolam, Fulvestrant, Pemetrexed, Cisplatin
Keywords
Advanced Breast Cancer, Advanced Lung Cancer, Mesothelioma, Lymphoma
Medical subject headings
Neoplasm Metastasis, Lymphoma, Non-Hodgkin, Breast Neoplasms, Mesothelioma, Malignant, Carcinoma, Non-Small-Cell Lung, Mesothelioma, Lymphoma

What participants receive

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

  • LY3023414Drug

    Administered orally. Dose of 20 to 600 mg, as determined in Part A.

  • MidazolamDrug

    0.2 mg administered orally once before LY3023414 on Day 1 and once after LY3023414 on Day 15.

  • FulvestrantDrug

    500 mg administered IM on Day 1 and Day 15 in cycle 1 and Day 1 every 28 days for additional cycles.

  • PemetrexedDrug

    Also called Alimta

    500 mg/m2 administered IV once on Day 1 every 21 days

  • CisplatinDrug

    75 mg/m2 administered IV once on Day 1 every 21 days

  • AbemaciclibDrug

    Also called LY2835219

    Administered orally

  • LetrozoleDrug

    Administered orally

Study groups in NCT01655225
Study groupRoleWhat they receive
Part A: LY3023414 Once DailyExperimentalLY3023414 administered orally once daily (QD) at escalating doses for two 21 day cycles to participants with advanced/metastatic cancer (including lymphoma); participants receiving benefit may continue until disease progression or discontinuation.
Receives: Drug: LY3023414
Part A2: LY3023414 Twice DailyExperimentalLY3023414 administered orally twice daily (BID) at escalating doses for two 21 day cycles to participants with advanced/metastatic cancer (including lymphoma); participants receiving benefit may continue until disease progression or discontinuation.
Receives: Drug: LY3023414
Part B1 : LY3023414 + MidazolamExperimentalLY3023414 administered orally BID for two 21 day cycles to participants with advanced/metastatic cancer; participants receiving benefit may continue until disease progression or discontinuation. Dose based on Part A. 0.2 milligrams (mg) midazolam administered orally once before LY3023414 on Day 1 and once after LY3023414 on Day 15.
Receives: Drug: LY3023414; Drug: Midazolam
Part B2: LY3023414 + FulvestrantExperimentalLY3023414 administered orally BID for two 28 day cycles to participants with advanced/metastatic breast cancer; participants receiving benefit may continue until disease progression or discontinuation. 500 mg fulvestrant administered IM once every 28 days.
Receives: Drug: LY3023414; Drug: Fulvestrant
Part B3: LY3023414ExperimentalLY3023414 administered orally BID for two 21 day cycles to participants with malignant mesothelioma; participants receiving benefit may continue until disease progression or discontinuation.
Receives: Drug: LY3023414
Part B4: LY3023414 + pemetrexed/cisplatinExperimentalLY3023414 administered orally BID for two 21 day cycles to participants with malignant mesothelioma; participants receiving benefit may continue until disease progression or discontinuation. 500 mg/m2 pemetrexed and 75 mg/m2 administered IV once every 21 days.
Receives: Drug: LY3023414; Drug: Pemetrexed; Drug: Cisplatin
Part B5: LY3023414ExperimentalLY3023414 administered orally BID for two 21 day cycles to participants with indolent non-Hodgkin's lymphoma; participants receiving benefit may continue until disease progression or discontinuation.
Receives: Drug: LY3023414
Part B6: LY3023414ExperimentalLY3023414 administered orally BID for two 21 day cycles to participants with squamous NSCLC; participants receiving benefit may continue until disease progression or discontinuation.
Receives: Drug: LY3023414
Part B7: LY3023414 + Abemaciclib + LetrozoleExperimentalLY3023414 administered orally BID with abemaciclib administered orally BID and letrozole administered orally once a day for two 28 day cycles to participants with breast cancer; participants receiving benefit may continue until disease progression or discontinuation.
Receives: Drug: LY3023414; Drug: Abemaciclib; Drug: Letrozole

What is being measured

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

  1. Recommended Phase 2 dose

    Measured: Baseline to disease progression or participant discontinuation (estimated 9 weeks)

Secondary outcomes (4)
  1. Pharmacokinetics: Maximum concentration (Cmax)

    Measured: Predose up to 12 hours postdose

  2. Pharmacokinetics: Time of maximal concentration

    Measured: Predose up to 12 hours postdose

  3. Number of participants with tumor response

    Measured: Baseline to disease progression or participant discontinuation (estimated 9 weeks)

  4. Potential of LY3023414 to inhibit CYP3A4-mediated metabolism

    Measured: Baseline through Cycle 1

Timeline

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

  1. First posted1 Aug 2012 (estimated)
  2. Study start31 Jul 2012
  3. Primary completion4 Apr 2019
  4. Study completion2 Feb 2022

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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
156 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01655225
Sponsor's protocol ID
13517
Other IDs
I6A-MC-CBBA
Status last verified
Apr 2022
First submitted
19 Jul 2012
Last updated
8 Apr 2022
Results posted
No
Data monitoring committee
No

Publications

  • Zauderer MG, Alley EW, Bendell J, Capelletto E, Bauer TM, Callies S, Szpurka AM, Kang S, Willard MD, Wacheck V, Varghese AM. Phase 1 cohort expansion study of LY3023414, a dual PI3K/mTOR inhibitor, in patients with advanced mesothelioma. Invest New Drugs. 2021 Aug;39(4):1081-1088. doi: 10.1007/s10637-021-01086-6. Epub 2021 Mar 4.

    PubMed 33660194

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing LY3023414, Midazolam and Fulvestrant in people with Advanced Cancer and Metastatic Cancer, run by Eli Lilly and Company at 8 sites in 3 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 14 inclusion and 12 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 8 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States, Italy, Puerto Rico. 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?

Recommended Phase 2 dose (time frame: Baseline to disease progression or participant discontinuation (estimated 9 weeks)). 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 NCT01655225, 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 8 Apr 2022.

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Clinical Trial NCT01655225 | AzTrials