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Advanced Solid Malignant TumorsPhase 1NCT01290471

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

A Phase 1 study testing U3-1565 in people with Advanced Solid Malignant Tumors and Advanced Ovarian Cancer, run by Daiichi Sankyo at 4 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 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
U3-1565
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
4 sitesUnited States
Study dates
Jan 2011to Jan 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

  • 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.
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  • 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.

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Karmanos Cancer Center

    Detroit, Michigan, 48201

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Univ. Oklahoma Health Science Center

    Oklahoma City, Oklahoma, 73104

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
U3-1565

What participants receive

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

  • U3-1565Drug

    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.

Study groups in NCT01290471
Study groupRoleWhat they receive
Part 1 Dose EscalationExperimentalDose escalation of U3 1565 will follow a modified 3+3 study design with a starting intravenous (IV) dose of 2 mg/kg. A maximum of 2 new subjects will receive their first dose of U3-1565 per 24-hour period during the dose-escalation phase. Subsequent escalating doses of 8, 16, and 24 mg/kg are planned. Three to 6 subjects will be enrolled in 4 sequential dose level cohorts.
Receives: Drug: U3-1565
Part 2a Dose ExpansionExperimentalFor Part 2a, 6 or 12 subjects with advanced solid malignant tumors will be enrolled and treated at the MTD or MAD to further define the safety and tolerability of U3-1565. These additional subjects are expected to permit the detection of relatively rare toxicities that would not likely be observed during the dose escalation part of the study, whose 3+3 design implies a maximum of 6 subjects only will be treated at the MTD or MAD. Six subjects will be treated; however, if toxicities meeting the definition of DLT are observed during the first cycle of treatment, 6 more subjects will be treated for a total of 12 subjects.
Receives: Drug: U3-1565
Part 2b Dose Expansion and Anti-tumor ImpactExperimentalFor Part 2b, up to 30 subjects with advanced solid malignant tumors, with a preference for those with advanced ovarian cancer, will be enrolled and treated at the MTD or MAD. This number of subjects should allow demonstrating U3-1565 has anti-tumor impact by showing treatment-induced changes in pharmacodynamic biomarkers and clinical activity. Ovarian cancer may be more likely to be impacted by U3 1565 than other tumors, considering that in this cancer, high levels of HB-EGF have been associated with an unfavorable clinical outcome. Six subjects will be initially treated; at which point, a safety analysis will be conducted after these initial subjects have completed the first cycle of treatment, to allow the reevaluation of the appropriateness of the dosing level.
Receives: Drug: U3-1565

What is being measured

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

  1. 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

    Measured: 6 months

Secondary outcomes (4)

  1. determine the maximum tolerated dose (MTD) or tolerability of maximum administered dose (MAD).

    Measured: 12 months

  2. Greatest percent reduction in the sum of longest diameters (SLD) of measurable tumors, if applicable, after U3 1565 treatment

    Measured: 24 months

  3. 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.

    Measured: 24 months

  4. Changes in tumor perfusion and vascularity after U3-1565 treatment using Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE MRI)

    Measured: 24 months

Timeline

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

  1. First posted7 Feb 2011 (estimated)
  2. Study startJan 2011
  3. Primary completionJan 2013
  4. Study completionJan 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
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01290471
Sponsor's protocol ID
U31565-A-U101
Status last verified
May 2014
First submitted
2 Feb 2011
Last updated
19 May 2014
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing U3-1565 in people with Advanced Solid Malignant Tumors and Advanced Ovarian Cancer, run by Daiichi Sankyo at 4 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 9 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 19 May 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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?

Number (percent) of subjects experiencing adverse events (AEs) after treatment with U3-1565 (time frame: 6 months). 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 NCT01290471.

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 19 May 2014.

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