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Solid TumorPhase 1NCT01971515

First-in-Human Dose Escalation Trial in Subjects With Advanced Malignancies

A Phase 1 study testing MSC2363318A, MSC2363318A plus Trastuzumab and MSC2363318A plus Tamoxifen in people with Solid Tumor, run by EMD Serono at 15 sites in United States.

Completed

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

Official record
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Trial summary

This is a Phase 1, first-in-human, open-label, non-randomized, dose escalation, trial to explore the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and clinical activity signals of MSC2363318A. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumor
What is being tested?
MSC2363318A, MSC2363318A plus Trastuzumab and MSC2363318A plus Tamoxifen
Could I receive a placebo?
No, everyone receives an active treatment
How many people
101 participants
Where
15 sitesUnited States
Study dates
13 Dec 2013to 9 Aug 2018
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

  • Age greater than or equal to (>=)18 years
  • Confirmed diagnosis of advanced malignancies that may be controlled with p70S6K or Akt inhibition based on already identified molecular alteration known to affect the PAM pathway, such as:: such as: such as: phosphate and tensin homolog (PTEN), phosphoinositide 3-Kinase catalytic subunit alpha isoform (PIK3CA), protein kinase B 1 (Akt 1), Akt 3, mammalian target of rapamycin (mTOR), tumor sclerosis complex 1 (TSC1), tumor sclerosis complex 2 (TSC2), in subjects who have received at least all treatment options considered to be standard therapy, unless some available treatment are not acceptable to the subject. For the dose escalation portion of the trial, subjects must have received the standard therapy unless intolerant or contraindicated.
  • Part 2, Cohort 1: For subjects with only PAM pathway alterations, subjects must have only PAM alterations, excluding Akt2 activating mutations or amplifications, and no other genomic alterations.
  • Part 2, Cohort 2: Histologically confirmed local laboratory testing (immunohistochemistry 3+ staining and/or fluorescence in situ hybridization ratio >= 2.0) HER2+ metastatic breast cancer subjects who are resistant to trastuzumab-containing treatment and progressed on trastuzumab, pertuzumab, a taxane, and/or trastuzumab emtansine. There is no limit regarding the number of prior lines of therapy. Subjects may be enrolled regardless of whether or not their tumor harbors a PAM pathway alteration (documentation of PAM pathway alteration for this cohort is not required).
  • Part 2, Cohort 3: Histologically and/or cytologically confirmed diagnosis of breast cancer with hormone receptor-positive status (ER and/or PgR positive) and HER2-negative status with prior exposure to tamoxifen and/or an aromatase inhibitor and/or an aromatase inhibitor plus palbociclib. Prior treatment with tamoxifen in the neoadjuvant setting is allowed but must have been discontinued for at least 1 year prior to the first dose.
  • Measurable disease using clinically appropriate criteria for the type of malignancy, RECIST version 1.1 for solid tumors and Cheson 2007 for lymphoma
Show all 10Show fewer
  • A tumor accessible for biopsies and consent to undergo tumor biopsies before and during MSC2363318A treatment. Subjects who do not have a tumor suitable for biopsy (such as, but not limited to, high procedural risk, inaccessible site for needle biopsy, etc.) but are otherwise eligible for this study may be considered for enrollment on a case-by-case basis after discussion with the Medical Monitor of the study
  • Ability to read and understand the informed consent form and willingness and ability to give informed consent and demonstrate comprehension of the trial before undergoing any trial activities
  • Negative blood pregnancy test at the screening visit for women of childbearing potential
  • Willingness to avoid pregnancy and breast feeding beginning two weeks before the first MSC2363318A dose and ending three months after the last trial treatment. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must use adequate contraception in the judgment of the Investigator, such as a two barrier method or a one barrier method with spermicide or intrauterine device during trial treatment dosing and for 3 months after the last dose of the study.

Who cannot join

  • Eastern Cooperative Oncology Group Performance Status >=2
  • Previous therapy with:
  • Chemotherapy, immunotherapy, biologic therapy, or any other anticancer therapy within 2 weeks (or five elimination half lives for noncytotoxics, whichever is shorter) of Day 1 of trial drug treatment (6 weeks for nitrosureas or mitomycin). Subjects on therapy with trastuzumab (trastuzumab cohort) may continue with trastuzumab during the screening phase of the study. Subjects on endocrine therapy may continue with antihormonal therapy until Day 1 of the study.
  • Any investigational agent within 3 weeks of Day 1 of trial drug treatment
  • Extensive prior radiotherapy on more than 30 percent of bone marrow reserves, or prior bone marrow/stem cell transplantation within 5 years from enrolment
  • Palliative radiation therapy within 2 weeks of Day 1 of trial drug treatment
Show all 19Show fewer
  • Known tumor EGFR, KRAS, and/or Akt2 mutations or amplification
  • Ongoing toxicity due to a prior therapy, unless returned to baseline or Grade 1. Grade 2 toxicities (e.g., alopecia or peripheral neuropathy) that are not likely to increase the subject's safety risk while receiving trial treatment may be accepted after Sponsor approval.
  • Major surgical intervention or participation in a therapeutic clinical trial within 28 days from Day 1 of the first dose of MSC2363318A
  • Bone marrow impairment, renal impairment, liver function abnormality and impaired cardiac function as defined in the protocol
  • History of cerebral vascular accident or stroke within the previous 2 years
  • Uncontrolled hypertension
  • History of Grade 3 or 4 allergic reactions attributed to compounds of similar chemical or biologic composition as MSC2363318A
  • Known symptomatic central nervous system (CNS) metastases
  • History of difficulty swallowing, malabsorption or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the investigational product
  • Known human immunodeficiency virus, viral hepatitis, or tuberculosis positivity
  • Legal incapacity or limited legal capacity
  • Any other condition which, in the opinion of the Investigator, might impair the subject's tolerance of trial treatment, the safety of the individual subject or the outcome of the trial. (including but not limited to: history of major depressive episode, bipolar disorder, obsessive-compulsive disorder, schizophrenia, suicidal attempt or ideation, homicidal ideation, or >= Common Terminology Criteria for Adverse Events [CTCAE] Grade 3 anxiety)
  • Immediate prior therapy with a PAM pathway inhibitor (i.e., the subject is excluded if the last treatment regimen, prior to MSC2363318A, was a PAM pathway inhibitor, or if the last PAM pathway inhibitor that the subject was treated with occured less than 2 months prior to Day 1 of trial drug treatment).

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

United States15 sites

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Fletcher Allen Health Care, Inc.

    Burlington, Vermont, 05401

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Mary Crowley Cancer Research Center

    Dallas, Texas, 75251

  • Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

  • Metairie Oncology

    Metairie, Louisiana, 70006

  • Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • Mount Sinai

    New York, New York, 10029

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • University of California at San Diego, Moores Cancer Center

    San Diego, California, 92093

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Phase I, First-in-Human, Dose Escalation Trial of MSC2363318A, a Dual p70S6K/Akt Inhibitor, in Subjects With Advanced Malignancies

This is a Phase 1, first-in-human, open-label, non-randomized, dose escalation, trial to explore the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and clinical activity signals of MSC2363318A.

Conditions
Solid Tumor
Being tested
MSC2363318A, MSC2363318A plus Trastuzumab, MSC2363318A plus Tamoxifen
Keywords
MSC2363318A, Maximum tolerated dose, Dose limiting toxicities, Recommended phase 2 dose, M2698, Metastatic Breast Cancer, HER2+ Metastatic Breast Cancer, Hormone refractory ER/PR+ breast cancer, Tamoxifen, PAM Pathway Alteration(s), PAM Pathway, Targeted Therapy, P70S6K, AKT Inhibition, PI3K Pathway, HER2+ Trastuzumab Resistance
Medical subject headings
Breast Neoplasms

What participants receive

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

  • MSC2363318ADrug

    Also called M2698

    Part 1: MSC2363318A will be administered orally once daily for repeated 21-day cycles until intolerable toxicity or disease progression. Additional dose escalations will continue until Maximum Tolerated Dose (MTD) is reached, the food effect will be investigated in a separate group.

    Part 2 (Cohort 1): MSC2363318A will be administered orally once daily for repeated 21-day cycles until intolerable toxicity or disease progression in subjects with PAM pathway alterations.

    Dose reductions or treatment interruptions will be made at the discretion of the Investigator. If treatment interruption is required due to an acute or less severe but intolerable MSC2363318A-related event, at least a 1-week break is recommended. If, at retreatment, the dose reduction is not required, then the "continuous daily dosing regimen" may be replaced with an "intermittent dose regimen" of 2 weeks on, 1 week off (i.e. daily dosing from Day 1 to Day 15 followed by no dosing on Day 16 to Day 21 of the cycle).

  • MSC2363318A plus TrastuzumabDrug

    Part 2 Cohort 2: MSC2363318A will be administered orally once daily for repeated 21-day cycles in combination with Trastuzumab.

    Dose reductions or treatment interruptions will be made at the discretion of the Investigator. If treatment interruption is required due to an acute or less severe but intolerable MSC2363318A-related event, at least a 1-week break is recommended. If, at retreatment, the dose reduction is not required, then the "continuous daily dosing regimen" may be replaced with an "intermittent dose regimen" of 2 weeks on, 1 week off (i.e. daily dosing from Day 1 to Day 15 followed by no dosing on Day 16 to Day 21 of the cycle).

    Trastuzumab is a recombinant IgGI kappa humanized monoclonal antibody administered weekly by intravenous infusion.

  • MSC2363318A plus TamoxifenDrug

    Part 2 Cohort 3: MSC2363318A will be administered orally once daily for repeated 21-day cycles in combination with Tamoxifen.

    Dose reductions or treatment interruptions will be made at the discretion of the Investigator. If treatment interruption is required due to an acute or less severe but intolerable MSC2363318A-related event, at least a 1-week break is recommended. If, at retreatment, the dose reduction is not required, then the "continuous daily dosing regimen" may be replaced with an "intermittent dose regimen" of 2 weeks on, 1 week off (i.e. daily dosing from Day 1 to Day 15 followed by no dosing on Day 16 to Day 21 of the cycle).

    Tamoxifen is a nonsteroidal antiestrogen administered daily by oral administration.

Study groups in NCT01971515
Study groupRoleWhat they receive
MSC2363318AExperimentalNot described
Receives: Drug: MSC2363318A
MSC2363318A plus TrastuzumabExperimentalNot described
Receives: Drug: MSC2363318A plus Trastuzumab
MSC2363318A plus TamoxifenExperimentalNot described
Receives: Drug: MSC2363318A plus Tamoxifen

What is being measured

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

  1. Number of dose limiting toxicities (DLTs) in Dose Escalation and Trastuzumab or Tamoxifen combination arms

    Measured: Up to Day 21 of Cycle 1

  2. Number of subjects with Treatment-emergent adverse events (TEAEs), Serious Adverse Events (SAEs), and deaths in cohort for subjects with PAM pathway alterations

    Measured: Baseline up to Day 30 after the last dose of study treatment

Secondary outcomes (16)

  1. Observed Maximum Plasma Concentration (Cmax)

    Measured: Days 1, 2, 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2, Cycle 3

  2. Time To Reach Maximum Plasma Concentration (Tmax)

    Measured: Days 1, 2, 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2, Cycle 3

  3. Area Under Plasma Concentration Versus Time Curve From Time Zero to Last Sampling Time (AUC0-t)

    Measured: Days 1, 2, 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2, Cycle 3

  4. Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf)

    Measured: Days 1, 2, 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2, Cycle 3

  5. Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau)

    Measured: Days 1, 2, 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2, Cycle 3

  6. Apparent Terminal Half-life ( t1/2)

    Measured: Days 1, 2, 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2, Cycle 3

  7. Apparent Oral Clearance (CL/F)

    Measured: Days 1, 2, 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2, Cycle 3

  8. Apparent Oral Clearance Steady State (CLss/F)

    Measured: Days 1, 2, 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2, Cycle 3

  9. Apparent Volume of Distribution (Vz/F)

    Measured: Days 1, 2, 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2, Cycle 3

  10. Apparent Volume of Distribution at Steady State (Vss/F)

    Measured: Days 1, 2, 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2, Cycle 3

  11. Factor to Assess the Increase of Drug Concentration in Plasma Until Steady State is Reached [Racc(AUC)]

    Measured: Days 1, 2, 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2, Cycle 3

  12. Factor to Assess the Maximal Increase of Drug Concentration in Plasma [Racc (Cmax)]

    Measured: Days 1, 2, 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2, Cycle 3

  13. Number of subjects with best overall response according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v 1.1) or Cheson 2007

    Measured: Evaluation were performed on Day 1 of every alternate cycle until tumor progression

  14. Percentage of subjects with clinical benefit

    Percentage of subjects with clinical benefit is defined as subjects with complete response (CR) or partial response (PR) at week 12, based on tumor assessment as determined by RECIST version 1.1 or Cheson 2007.

    Measured: Week 12

  15. Disease control rate (DCR) for Cohort 2 only

    Measured: Week 6

  16. Progression-free survival (PFS) rate for Cohorts 2 and 3 only

    Measured: up to 6 months

Timeline

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

  1. First posted29 Oct 2013 (estimated)
  2. Study start13 Dec 2013
  3. Primary completion9 Aug 2018
  4. Study completion9 Aug 2018

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
101 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01971515
Sponsor's protocol ID
EMR100018-001
Status last verified
Sep 2018
First submitted
23 Oct 2013
Last updated
19 Sep 2018
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Tsimberidou AM, Shaw JV, Juric D, Verschraegen C, Weise AM, Sarantopoulos J, Lopes G, Nemunaitis J, Mita M, Park H, Ellers-Lenz B, Tian H, Xiong W, Kaleta R, Kurzrock R. Phase 1 study of M2698, a p70S6K/AKT dual inhibitor, in patients with advanced cancer. J Hematol Oncol. 2021 Aug 18;14(1):127. doi: 10.1186/s13045-021-01132-z.

    PubMed 34407844

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MSC2363318A, MSC2363318A plus Trastuzumab and MSC2363318A plus Tamoxifen in people with Solid Tumor, run by EMD Serono at 15 sites 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 10 inclusion and 19 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 19 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites 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?

Number of dose limiting toxicities (DLTs) in Dose Escalation and Trastuzumab or Tamoxifen combination arms (time frame: Up to Day 21 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 NCT01971515, 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 19 Sep 2018.

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