Brief Title
Safety and Tolerability of DS-7423 in Subjects With Advanced Solid Malignant Tumors
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
Brief 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 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.
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Adverse Events
Secondary Outcome
Plasma pharmacokinetics of DS-7423
Condition
Solid Tumor
Intervention
DS-7423
Study Arms / Comparison Groups
DS7423
Description:
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
42
Start Date
July 2011
Completion Date
November 2013
Primary Completion Date
November 2013
Eligibility Criteria
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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
- 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)
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
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Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01364844
Organization ID
DS7423-A-U101
Responsible Party
Sponsor
Study Sponsor
Daiichi Sankyo, Inc.
Study Sponsor
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Verification Date
February 2014