Clinical trial NCT01290471: Study to Assess the Safety and Tolerability of U3-1565 in Subjects With Advanced Solid Malignant Tumors
Official title: Phase 1, Open Label Study to Assess the Safety and Tolerability of U3 1565 in Subjects With Advanced Solid Malignant Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Malignant Tumors
Advanced Ovarian Cancer
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2011-02-07
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase 1, open label study to assess the safety and tolerability of U3 1565, determine maximum tolerated dose (MTD) or establish maximum administered dose (MAD) safety and tolerability.

Detailed description: 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.

Eligibility criteria: 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 U/mL.
* 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 treatment.
* 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 screening.
* 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 equation.

- 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.

Primary outcomes:
measure: Number (percent) of subjects experiencing adverse events (AEs) after treatment with U3-1565
timeFrame: 6 months
Secondary outcomes:
measure: determine the maximum tolerated dose (MTD) or tolerability of maximum administered dose (MAD).
timeFrame: 12 months
measure: Greatest percent reduction in the sum of longest diameters (SLD) of measurable tumors, if applicable, after U3 1565 treatment
timeFrame: 24 months
measure: Changes in pharmacodynamic biomarkers in blood and other body fluid specimens
timeFrame: 24 months
measure: Changes in tumor perfusion and vascularity after U3-1565 treatment using Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE MRI)
timeFrame: 24 months
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Karmanos Cancer Center
state: Michigan
city: Oklahoma City
country: United States
facility: Univ. Oklahoma Health Science Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
Study officials:
affiliation: Daiichi Sankyo
name: Giorgio Senaldi, MD, PhD
role: STUDY_DIRECTOR
References: