Study to Assess the Safety and Tolerability of U3-1565 in Subjects With Advanced Solid Malignant Tumors

Advanced Ovarian Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01290471
• Other study ID #: U31565-A-U101
• Status: Completed
• Phase: Phase 1
• First received: February 2, 2011
• Last updated: May 16, 2014
• Start date: January 2011
• Est. completion date: January 2013

Study information

• Verified date: May 2014
• Source: Daiichi Sankyo Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Advanced Ovarian Cancer
• Advanced Solid Malignant Tumors
• Neoplasms

Intervention

Drug:
• U3-1565
U3 1565 will be provided as a sterile, frozen solution. Each glass vial will contain 1.1 mL (1 mL extractable) of study medication with a concentration of 100 mg/mL. U3 1565 will be diluted in a final volume of 100 mL and administered by continuous IV infusion over 60 minutes. Infusion times can be extended to a maximum of 120 minutes for subjects unable to tolerate the 60 minute infusion.

Locations

Country	Name	City	State
United States	Karmanos Cancer Center	Detroit	Michigan
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Univ. Oklahoma Health Science Center	Oklahoma City	Oklahoma
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Daiichi Sankyo Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number (percent) of subjects experiencing adverse events (AEs) after treatment with U3-1565	Number (percent) of subjects experiencing adverse events (AEs) after treatment with U3-1565	6 months	No
Secondary	determine the maximum tolerated dose (MTD) or tolerability of maximum administered dose (MAD).		12 months	No
Secondary	Greatest percent reduction in the sum of longest diameters (SLD) of measurable tumors, if applicable, after U3 1565 treatment		24 months	No
Secondary	Changes in pharmacodynamic biomarkers in blood and other body fluid specimens	Changes in pharmacodynamic biomarkers in blood and other body fluid specimens (such as soluble HB-EGF and CA125 in serum and ascites) and tumor biopsies after U3 1565 treatment.	24 months	No
Secondary	Changes in tumor perfusion and vascularity after U3-1565 treatment using Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE MRI)		24 months	No