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Solid TumorPhase 1NCT01364844

Safety and Tolerability of DS-7423 in Subjects With Advanced Solid Malignant Tumors

A Phase 1 study testing DS-7423 in people with Solid Tumor and Colorectal Cancer, run by Daiichi Sankyo at 3 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 will be a Phase 1, open-label study of DS-7423 to assess its safety and tolerability, identify a RP2D, (recommended Phase 2 Dose) and assess its Pharmacokinetics (PK) (what your body does to process the drugs and how your body gets them out of your system.) and pharmacodynamics (PDy) (Pharmacodynamics is a study… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumor, Colorectal Cancer, Endometrial Cancer
What is being tested?
DS-7423
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
3 sitesUnited States
Study dates
Jul 2011to Nov 2013
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 documented advanced solid malignant tumor refractory to standard treatment or for which no standard treatment is available
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1
  • Have adequate bone marrow function, defined as:
  • Platelet count >= 100 X 10^9/L Hemoglobin (Hb) level >= 9.0 g/dL ANC >= 1.5 X 10^9/L - Have adequate renal function, defined as: Creatinine clearance >= 60 mL/min, as calculated using the modified Cockroft Gault equation, ([{140 - age in yrs} x {actual weight in kg}] divided by [{72 x serum creatinine in mg/dL} multiply by 0.85 if female]), or creatinine =< 1.5 X ULN
  • Have adequate hepatic function, defined as: AST/ALT levels =< 3 X ULN (if liver metastases are present, =< 5 X ULN) Bilirubin =< 1.5 X ULN
  • Have adequate blood clotting function, defined as: Prothrombin time and activated partial thromboplastin time =< 1.5 X ULN
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  • Subjects should be able to provide written informed consent, comply with protocol visits and procedures, be able to take oral medication, and not have any active infection or chronic comorbidity that would interfere with therapy
  • Subjects (male and female) of childbearing potential must agree to use double-barrier contraceptive measures or avoid intercourse during the study and for 90 days after the last dose of study drug
  • 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 (IRB) approved informed consent form (ICF) (including Health Insurance Portability and Accountability Act (HIPAA) authorization, if applicable) before performance of any study-specific procedures or tests
  • Subjects must be willing to provide available preexisting diagnostic or resected tumor samples, such as formalin-fixed paraffin-embedded sections. Providing fresh tumor biopsy is optional for subjects in dose escalation cohorts. Pre- and posttreatment biopsies are optional for all the subjects in Dose Escalation cohorts but required for those in Dose Expansion cohorts
  • Additional Inclusion Criteria for Part 2 (Dose Expansion)
  • A pathologically documented advanced colorectal or endometrial cancer, with measurable disease based on RECIST criteria, Version 1.1, that is refractory to standard treatment
  • Agree to undergo pre- and posttreatment tumor biopsies

Who cannot join

  • History of second malignancy and primary central nervous system malignancies, except adequately treated nonmelanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated, with no evidence of disease for >= 3 years
  • Gastrointestinal diseases that could affect the absorption of DS-7423
  • Subjects with a fasting glucose > 126 mg/dL (> 7 mmol/L)
  • History of diabetes mellitus (Type I or II) or hemoglobin A1c (HbA1c) > 7.0%
  • Tested positive for hepatitis B or C serological markers (HBsAg or antiHCV)
  • Recipient of live vaccine within 1 month of or during study drug treatment
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  • Concomitant use of chronic systemic corticosteroids
  • Subjects requiring daily supplemental oxygen
  • Recipient of a stem cell or bone marrow transplant
  • Has 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. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with steroids may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 4 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment (2 weeks for stereotactic radiotherapy)
  • Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI CTCAE, Version 4.0, grade =< 1 or baseline. Subjects with chronic grade 2 toxicities may be eligible per the discretion of the investigator or sponsor (eg, grade 2 chemotherapy-induced neuropathy)
  • 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. Previous and concurrent use of hormone replacement therapy, the use of gonadotropin-releasing hormone modulators for prostate cancer, and the use of somatostatin analogs for neuroendocrine tumors are permitted if such therapy has not been changed within 60 days before study drug treatment
  • Therapeutic radiation therapy 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 inducers or strong inhibitors of cytochrome P450 (CYP) 3A4/5, and CYP2C8
  • Prolongation of corrected QT interval by Fridericia's method (QTcF) at rest, where the mean QTcF interval is > 450 millisecond (ms) for males and > 470 ms for females based on triplicate ECG
  • Pregnant or breastfeeding
  • Substance abuse or medical, psychological, or social conditions that may, in the opinion of the investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results
  • Prior NCI CTCAE, Version 4.0, grade 3/4 toxicity from a dual phosphatidylinositol 3 kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor (including, but not limited to, BEZ-235, XL765, GDC-0980, SF1126, GSK2126458, PF4691502, and PF05212384), requiring dose reduction and/or study discontinuation
  • Additional Exclusion Criteria for Part 2 (Dose Expansion)
  • Prior treatment with a dual PI3K/ mTOR inhibitor (including, but not limited to, BEZ-235, XL765, GDC-0980, SF1126, GSK2126458, PF4691502, and PF05212384)

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Phase 1, Open-Label, Multiple-Escalating-Dose Study of DS-7423, an Orally Administered Dual PI3K/mTOR Inhibitor, in Subjects With Advanced Solid Tumors

This will be a Phase 1, open-label study of DS-7423 to assess its safety and tolerability, identify a RP2D, (recommended Phase 2 Dose) and assess its Pharmacokinetics (PK) (what your body does to process the drugs and how your body gets them out of your system.) and pharmacodynamics (PDy) (Pharmacodynamics is a study of what a drug does to your body) properties in subjects with advanced solid malignant tumors. This study will include 2 parts: part 1-Dose Escalation and part 2-Dose Expansion.

Study Hypothesis: DS-7423 will be safe and tolerable, and will exhibit acceptable PK and PDy properties in subjects with advanced solid malignant tumors for whom standard therapy has failed or for whom no standard therapy exists.

Read the detailed description

Part 1 : Dose-escalation of DS-7423 to determine maximum tolerated dose (MTD) in subjects with advanced solid tumors Part 2 : Dose Expansion: The purpose of Part 2 of this clinical research study is to confirm the safety and tolerability of the MTD of DS-7423 identified in Part 1, and measure the effects of DS-7423 on your cancer. Part 2 will be conducted in subjects with advanced colorectal or endometrial cancer.

Being tested
DS-7423
Medical subject headings
Colorectal Neoplasms, Endometrial Neoplasms

What participants receive

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

  • DS-7423Drug

    oral capsule 1mg, 8mg, 48mg, and 80mg strengths administered once daily

Study groups in NCT01364844
Study groupRoleWhat they receive
DS7423ExperimentalNot described
Receives: Drug: DS-7423

What is being measured

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

  1. Adverse Events

    All adverse events will be graded according to the NCI-CTCAE, version 4.0

    Measured: 30 days after last dose

Secondary outcomes (6)

  1. Plasma pharmacokinetics of DS-7423

    The various pharmacokinetic parameters will be calculated from plasma concentrations of DS-7423 using non-compartmental analyses.

    Measured: Cycle 1 - days 1, 2, 8, and 15; Cycle 2 - day 1; end of study

  2. Effects of DS-7423 on glucose metabolism

    The effects of DS-7423 on glucose metabolism will be determined by measuring glucose and C-peptide levels

    Measured: Cycle 1 Days 1, 2, and 15; and end-of-study

  3. Pharmacodynamic effects of DS-7423 in surrogate tissues

    The pharmacodynamic effects of DS-7423 will be determined by measuring phosphorylation of Akt in platelet-rich plasma

    Measured: Cycle 1 Days 1, 2, and 15

  4. Pharmacodynamic effects of DS-7423 in tumors

    The pharmacodynamic effects of DS-7423 will be determined by measuring tumor glucose uptake using (18F) fluorodeoxyglucose-positron emission tomography

    Measured: Baseline and Cycle 1 Day 4

  5. Part 2 - Objective response rate in subjects with advanced colorectal and endometrial cancer

    Objective response rate = the sum of complete response [CR] and partial response [PR] rates as measured using Response Evaluation Criteria in Solid Tumors (RECIST) criteria Version 1.1

    Measured: Baseline and every 2 cycles of treatment for the first 8 cycles and then every 3 cycles thereafter until study drug discontinuation

  6. Part 2 - Pharmacodynamic effects of DS-7423 in tumors

    The pharmacodynamic effects of DS-7423 in tumors will be determined by measuring Akt, ribosomal protein S6 (S6), and proline-rich Akt substrate, 40 kDA (PRAS40) phosphorylation in pre- and posttreatment tumor biopsies

    Measured: Baseline and Cycle 1 Day 15

Timeline

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

  1. First posted3 Jun 2011 (estimated)
  2. Study startJul 2011
  3. Primary completionNov 2013
  4. Study completionNov 2013

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
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01364844
Sponsor's protocol ID
DS7423-A-U101
Status last verified
Feb 2014
First submitted
31 May 2011
Last updated
25 Feb 2014
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing DS-7423 in people with Solid Tumor and Colorectal Cancer, run by Daiichi Sankyo at 3 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 13 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 25 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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?

Adverse Events (time frame: 30 days after last dose). 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 NCT01364844.

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 25 Feb 2014.

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