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Advanced Solid TumorPhase 1NCT01588678

A Open-Label, Multiple Ascending Dose Study of DS-3078a, an Oral TORC1/2 Kinase Inhibitor, in Subjects With Advanced Solid Tumors or Lymphomas

A Phase 1 study testing DS-3078a in people with Advanced Solid Tumor and Lymphoma, run by Daiichi Sankyo at 1 site 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

DS-3078a will be evaluated as a single agent in subjects with advanced solid tumor malignancies or lymphomas refractory to standard treatment or for which no standard treatment is available. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumor, Lymphoma
What is being tested?
DS-3078a
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
1 siteUnited States
Study dates
Apr 2012to Jun 2014
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

  • A pathologically or cytologically documented advanced solid tumor or lymphoma that has relapsed from or is refractory to standard treatment or for which no standard treatment is available.
  • Men or women >=18 years old.
  • Eastern Cooperative Oncology Group (ECOG) performance status =<1
  • Have adequate bone marrow function, defined as:
  • Platelet count >=100 x 10^9/L for solid tumors and >=75 x 10^9/L for lymphomas,
  • Hemoglobin level >=9.0 g/dL, and ANC >=1.5 x 10^9/L for solid tumors and >=1.0 x 10^9/L for lymphomas.
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  • Have adequate renal function, defined as:
  • Creatinine clearance >=60 mL/min, or creatinine =<1.5 x ULN.
  • Have adequate hepatic function, defined as:
  • AST/ALT levels =<3 x ULN (=<5 x ULN if liver metastases are present) and
  • Bilirubin =<1.5 x ULN.
  • Have adequate blood clotting function, defined as prothrombin time and activated partial thromboplastin time =<1.5 x ULN.
  • Subjects must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects) and must sign and date an Institutional Review Board/Ethics Committee-approved informed consent form (including Health Insurance Portability and Accountability Act authorization, if applicable) before performance of any study specific procedures or tests.
  • For Part 2
  • A pathologically or cytologically documented advanced solid tumor or non-Hodgkin lymphoma, with measurable disease based on RECIST 1.1 or revised IWG criteria, that is refractory to standard treatment. The solid tumor types that will be included in the study are of the following kinds in which the mTOR signaling is frequently activated: endometrial, prostate, breast, gastric, cervical,ovarian, or neuroendocrine cancers, soft-tissue sarcoma, squamous cell NSCLC,renal cell carcinoma or other tumor types approved by the Sponsor.
  • Agree to undergo pre- and post-treatment tumor biopsies.

Who cannot join

  • History of primary central nervous system malignancies
  • Gastrointestinal diseases that could affect the absorption of DS-3078a in the opinion of the Investigator
  • Subjects with a fasting glucose >126 mg/dL (>7 mmol/L)
  • History of diabetes mellitus (type 1 or 2) or glycosylated hemoglobin >7.0% at screening
  • Positive test for hepatitis B surface antigen or hepatitis C antibody
  • Recipient of live vaccine within 1 month of or during study drug treatment
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  • Use of chronic systemic corticosteroids (use of nasal or inhaled steroids is permitted)
  • Subjects requiring daily supplemental oxygen
  • Recipient of an allogenic stem cell or bone marrow transplant
  • Presence of a concomitant medical condition that would increase the risk of toxicity, in the opinion of the Investigator or Sponsor
  • Clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms.
  • Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE v4 grade =<1 or baseline.
  • Systemic treatment with anticancer therapy, antibody-based therapy, retinoid therapy, or hormonal therapy within 3 weeks before study drug treatment; or treatment with nitrosoureas or mitomycin C within 6 weeks before study drug treatment; or treatment with small-molecule targeted agents within 2 weeks or 5 half-lives before study drug treatment, whichever is longer.
  • Therapeutic radiation or major surgery within 4 weeks before study drug treatment or palliative radiation therapy within 2 weeks before study drug treatment
  • Participation in a clinical study within 3 weeks (2 weeks or 5 half-lives, whichever is longer, for small-molecule targeted agents) before study drug treatment, or current participation in other investigational procedures
  • Concomitant treatment with strong inhibitors or inducers of cytochrome P450 3A4 and P glycoprotein
  • Less than 1 week since using systemically acting drugs that increase gastric pH, such as H2-blockers and proton pump inhibitors. Antacids should be avoided within 48 hours of the first dose of DS 3078a
  • Prolongation of corrected QT interval by Fridericia's method (QTcF) at rest, where the mean QTcF interval is >450 msec based on triplicate electrocardiogram (ECG)
  • Pregnant or breastfeeding
  • Substance abuse or medical, psychological, or social conditions that, in the opinion of the Investigator, may interfere with the subject's participation in the clinical study or evaluation of the clinical study results
  • For Part 2
  • Subjects who have had prior treatment with an mTOR catalytic site inhibitor or dual PI3K/mTOR inhibitor (including, but not limited to, OSI-027, INK128, ADZ8055,AZD2014, WYE12513, PP242, BEZ-235, DS-7423, XL765, GDC-0980, SF1126, GSK2126458, PF4691502, and PF05212384) will be disqualified from entering the study.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • South Texas Accelerated Research Therapeutics

    San Antonio, Texas, 78229

Other trials in United States

About this study

Official title: A Phase 1, Open-Label, Multiple Ascending Dose Study of DS-3078a, an Oral TORC1/2 Kinase Inhibitor, in Subjects With Advanced Solid Tumors or Lymphomas

DS-3078a will be evaluated as a single agent in subjects with advanced solid tumor malignancies or lymphomas refractory to standard treatment or for which no standard treatment is available.

Read the detailed description

This is a Phase 1, open-label study of DS-3078a to assess safety and tolerability, identify the maximum tolerated dose (MTD) and tentative recommended phase 2 dose (RP2D), and assess pharmacokinetic and pharmacodynamic properties in subjects with advanced solid tumor malignancies or lymphomas. The study will include 2 parts: Dose Escalation and Dose Expansion.

Being tested
DS-3078a
Keywords
endometrial, prostate, breast, gastric, cervical, ovarian, neuroendocrine cancers, soft-tissue sarcoma, squamous cell NSCLC, renal cell carcinoma, non-Hodgkin lymphoma
Medical subject headings
Lymphoma, Sarcoma, Carcinoma, Renal Cell, Lymphoma, Non-Hodgkin

What participants receive

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

  • DS-3078aDrug

    DS-3078a will be administered as oral capsules once daily and will be supplied in 5, 20, 50, and 150 mg capsules.

Study groups in NCT01588678
Study groupRoleWhat they receive
DS-3078aExperimentalPart 1 - Dose escalation of DS-3078a to determine the maximum tolerated dose (MTD) will be guided by the modified continuous reassessment method (mCRM) using a Bayesian logistic regression model (BLRM) following escalation with overdose control (EWOC) principle. Before starting mCRM, initial dose escalation will proceed following an accelerated titration in which single subjects will be enrolled into sequential dose levels with a dose increment of up to 100% from the previous dose. Upon completion of Part 1 with established MTD and tentative recommended phase 2 dose (RP2D), the Dose Expansion (Part 2) will begin with the intention of further assessing the safety and tolerability of DS-3078a, confirming the RP2D, determining the Pharmacodynamic response in tumor samples, and evaluating preliminary efficacy of DS-3078a in subjects.
Receives: Drug: DS-3078a

What is being measured

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

  1. Maximum tolerated dose

    To determine the maximum tolerated dose (MTD) and tentative recommended Phase 2 dose (RP2D) of DS 3078a

    Measured: 3 years

Secondary outcomes (8)

  1. determine the Cmax profile of DS 3078a

    determine the Cmax (maximum concentration) of DS-3078a administered under fed and unfed conditions

    Measured: 3 years

  2. effect on glucose metabolism

    determine the effect of DS-3078a on glucose metabolism by measuring serum glucose and C peptide

    Measured: 3 years

  3. assess pharmacodynamic effects tumor glucose uptake

    assess the pharmacodynamic effects of DS 3078a by determining tumor glucose uptake using (18F) fluorodeoxyglucose positron emission tomography (FDG-PET)

    Measured: 3 years

  4. assess tumor response

    assess tumor response to DS-3078a in subjects with advanced non-Hodgkin lymphomas or advanced solid tumor types in which the mammalian target of rapamycin (mTOR) signaling pathway is frequently activated

    Measured: 3 years

  5. assess pharmacodynamic effects v-akt murine thymoma viral oncogene

    assess the pharmacodynamic effects of DS 3078a by measuring v-akt murine thymoma viral oncogene homolog 1 (Akt) phosphorylation in platelet rich plasma (PRP)

    Measured: 3 years

  6. determine the AUC of DS 3078a

    determine the Area under the concentration versus time curve (AUC) of DS-3078a administered under fed and unfed conditions

    Measured: 3 years

  7. determine the Tmax of DS 3078a

    determine the time of maximum concentyration (Tmax) of DS-3078a administered under fed and unfed conditions

    Measured: 3 years

  8. determine the terminal half-life of DS 3078a

    determine the terminal half-life (T1/2) of DS-3078a administered under fed and unfed conditions

    Measured: 3 years

Timeline

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

  1. First posted1 May 2012 (estimated)
  2. Study startApr 2012
  3. Primary completionJun 2014
  4. Study completionJun 2014

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01588678
Sponsor's protocol ID
DS3078-A-U101
Status last verified
Apr 2015
First submitted
26 Apr 2012
Last updated
12 Feb 2019
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing DS-3078a in people with Advanced Solid Tumor and Lymphoma, run by Daiichi Sankyo 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 16 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: finished, as of the sponsor's last update on 12 Feb 2019. 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 (time frame: 3 years). 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 NCT01588678.

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 12 Feb 2019.

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