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Phase 1, Open Label Study to Assess the Safety and Tolerability of U3 1565 in Subjects With Advanced Solid Malignant Tumors

Phase 1
18 Years
Open (Enrolling)
Advanced Solid Malignant Tumors, Advanced Ovarian Cancer

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Trial Information

Phase 1, Open Label Study to Assess the Safety and Tolerability of U3 1565 in Subjects With Advanced Solid Malignant Tumors

This study will be conducted in 2 phases: a dose-escalation phase corresponding to Part 1
and a dose-expansion phase articulated in 2 concomitant parts (i.e., Parts 2a and 2b).

All parts of this study are single arm and open label. In all parts, tumor assessments will
be performed at screening and every 3 cycles thereafter, while the subject remains on study.
U3-1565 clinical activity will be assessed measuring tumor response by physical examination
and imaging according to RECIST version 1.1, if applicable.

Inclusion Criteria:

- Pathologically documented advanced solid malignant tumor refractory to standard
treatment or for which no standard treatment is available.

- Evaluable tumor for all parts of the study and, only for enrollment in Part 2b,
measurable tumor per RECIST version 1.1. However, subjects with advanced ovarian
cancer may be enrolled in Part 2b even if they do not have a tumor measurable per
RECIST version 1.1, as long as they have circulating levels of CA125 higher than 35

- Eastern Cooperative Oncology Group (ECOG) performance status =< 1.

- Men or women >= 18 years of age.

- Willing to provide pre-existing diagnostic or resected tumor samples, such as
paraffin embedded sections, if available.

- Willing, only for enrollment in Part 2b, to provide tumor biopsies before and after

- For female subjects, is postmenopausal (no menstrual period for a minimum of 12
months) or surgically sterile or, if otherwise of childbearing potential, has a
negative urine or serum pregnancy test at entry into the study, uses maximally
effective birth control during the course of the study, and is willing to use
contraception for 6 months following the last study drug administration.

- For male subjects, is surgically sterile or willing to use a double barrier
contraception method upon enrollment, during the course of the study, and for 6
months following the last study drug administration.

- Able to comprehend, sign, and date current 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.

Exclusion Criteria:

- History of lymphoma, leukemia, or other hematopoietic malignancy.

- History of human immunodeficiency virus (HIV) positivity. HIV testing is not
required for establishing eligibility.

- History of bleeding diathesis.

- History of idiosyncratic reactions to antibody drug products.

- History of stem cell or bone marrow transplant.

- History of myocardial infarction (MI) within 6 months before enrollment, symptomatic
congestive heart failure (CHF; New York Heart Association > Class II), unstable
angina or unstable cardiac arrhythmia requiring medication

- History of clinically significant pulmonary disease after receiving epidermal growth
factor receptor- (EGFR) targeting agents.

- Any concomitant medical condition that would increase the risk of toxicity, in the
opinion of the Investigator or Sponsor.

- Clinically active brain metastases defined as symptomatic or requiring treatment with
steroids or anti-convulsants.

- Unresolved toxicities from prior anti-cancer therapy defined as toxicities, except
alopecia, not yet resolved to National Cancer Institute (NCI) Common Terminology
Criteria for Adverse Events (CTCAE) version 4.0 Grade =< 1 or baseline values.
Subjects with chronic Grade 2 toxicities may be eligible at the discretion of the
Investigator or Sponsor (eg, Grade 2 chemotherapy-induced neuropathy).

- Mean QTcF (Fridericia's correction) intervals > 450 msec for male subjects and > 470
msec for female subjects, based on screening electrocardiogram (ECG).

- Moderate to severe cardiac valvular abnormalities identified by echocardiography at

- Hematological values, as follows:

Absolute neutrophil count (ANC) < 1.5 X 109/L Platelet count < 100 X 109/L Hemoglobin (Hb)
< 9 g/dL - Renal function, as follows: Creatinine > 1.5 X upper limit of normal (ULN) or
creatinine clearance < 60 mL/min, as calculated using the modified Cockcroft Gault

- Hepatic function, as follows: Aspartate aminotransferase (AST) > 3 X ULN (if liver
metastases are present, > 5 X ULN).

Alanine aminotransferase (ALT) > 3 X ULN (if liver metastases are present, >= 5 X ULN)

- Bilirubin > 1.5 X ULN

- Coagulation function, as follows:

Prothrombin time (PT) or partial thromboplastin time (PTT) > 1.5 X ULN

- Anti-cancer therapy, including antibody, retinoid, or hormonal treatment, within 3
weeks before enrollment. Prior and concurrent use of hormone replacement therapy,
use of gonadotropin-releasing hormone modulators for prostate cancer, and use of
somatostatin analogs for neuroendocrine tumors are permitted.

- Therapeutic radiation treatment within 4 weeks or palliative radiation treatment
within 2 weeks before enrollment, as long as radiation toxicities have resolved to
NCI CTCAE grade =< 1 or baseline values.

- Major surgery within 4 weeks before enrollment.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number (percent) of subjects experiencing adverse events (AEs) after treatment with U3-1565

Outcome Description:

Number (percent) of subjects experiencing adverse events (AEs) after treatment with U3-1565

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Giorgio Senaldi, MD, PhD

Investigator Role:

Study Director

Investigator Affiliation:

Daiichi Sankyo Inc.


United States: Food and Drug Administration

Study ID:




Start Date:

January 2011

Completion Date:

December 2014

Related Keywords:

  • Advanced Solid Malignant Tumors
  • Advanced Ovarian Cancer
  • Neoplasms
  • Ovarian Neoplasms



Fox Chase Cancer Center Philadelphia, Pennsylvania  19111
Sarah Cannon Research Institute Nashville, Tennessee  37203
Karmanos Cancer Center Detroit, Michigan  48201
Univ. Oklahoma Health Science Center Oklahoma City, Oklahoma  73104