Clinical Trials /

First in Man Study of SAR566658 Administered in Patients With CA6-Positive and Refractory Solid Tumor

NCT01156870

Description:

Primary Objective: To determine the maximum tolerated dose (MTD) of SAR566658 Secondary Objectives: - To characterize the safety profile of SAR566658 - To evaluate the pharmacokinetic profile of SAR566658 - To assess the potential immunogenicity of SAR566658 - To assess preliminary antitumor activity - To assess the effect of SAR566658 at recommended dose on CYP3A enzyme activity using midazolam - To assess safety in the alternative schedules of SAR566658 administration

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

First in Man Study of SAR566658 Administered in Patients With CA6-Positive and Refractory <span class="go-doc-concept go-doc-disease">Solid Tumor</span>

Title

  • Brief Title: First in Man Study of SAR566658 Administered in Patients With CA6-Positive and Refractory Solid Tumor
  • Official Title: Dose Escalation, Safety and Pharmacokinetic, First in Man Study, of SAR566658 Administered as a Single Agent by Intravenous Infusion in Adult Patients With CA6-Positive and Refractory Solid Tumors
  • Clinical Trial IDs

    NCT ID: NCT01156870

    ORG ID: TED10499

    NCI ID: U1111-1116-4129

    Trial Conditions

    Neoplasm Malignant

    Trial Interventions

    Drug Synonyms Arms
    SAR566658 SAR566658

    Trial Purpose

    Primary Objective:

    To determine the maximum tolerated dose (MTD) of SAR566658

    Secondary Objectives:

    - To characterize the safety profile of SAR566658

    - To evaluate the pharmacokinetic profile of SAR566658

    - To assess the potential immunogenicity of SAR566658

    - To assess preliminary antitumor activity

    - To assess the effect of SAR566658 at recommended dose on CYP3A enzyme activity using
    midazolam

    - To assess safety in the alternative schedules of SAR566658 administration

    Detailed Description

    The duration of the study for one patient in the dose escalation phase of the study will
    include a screening period of up to 3 weeks, a 3-week treatment cycle(s) and a 2-week
    treatment cycle(s). The patients may continue treatment until disease progression,
    unacceptable toxicity, or willingness to stop, followed by a minimum of 30-day follow-up. If
    a patient treated in dose escalation part or in an expansion cohorts, continues to benefit
    from the treatment at the time of Clinical Study Report, the patient can continue study
    treatment and will continue to undergo all assessments as per the study flowchart. Such
    patients will be followed at least until 30 days after the last IMP administration.

    Trial Arms

    Name Type Description Interventions
    SAR566658 Experimental SAR566658 will be administered by intravenous (IV) infusion according to three different schedules SAR566658

    Eligibility Criteria

    Inclusion criteria:

    Diagnosis of CA6-positive solid tumors as moderate to intense membrane staining of 15% of
    tumor cells for which no standard therapy is available.

    Exclusion criteria:

    - Eastem Cooperative Oncology Group performance status 2.

    - Any serious active disease or co-morbid condition, which, in the opinion of the
    Investigator, may interfere with the safety or the compliance with the study.

    - Poor bone marrow reserve.

    - Poor liver and renal function.

    - Pregnant or breast-feeding woman.

    - No use of effective birth control methods, when applicable.

    - No resolution of all specific toxicities (excluding alopecia) related to any prior
    anti-cancer therapy to Grade 1 according to the National Cancer Institute - Common
    Toxicity Criteria for Adverse Events (NCI-CTCAE) version 4.03 grade scaling.

    - Wash out period of less than 3 weeks from previous antitumor therapy or any
    investigational treatment, (and less than 6 weeks in case of prior nitroso-urea and
    or mitomycin C treatment). Patients will be eligible if hormonotherapy (ie, for
    breast tumors) is discontinued before first Investigational product administration.

    - Wash out period of less than 1 week from last palliative dose of radiotherapy.

    - Patients with respiratory insufficiency defined by a decrease more than 50% compared
    to theoretical baseline pulmonary volumes and theoretical baseline Diffusing capacity
    of the Lung for Carbon monoxyde.

    - Any lung radiotherapy in patient's cancer history.

    - Patients with previous history or active interstitial lung disease or pulmonary
    fibrosis.

    - Patients with abnormal cardiac function defined by a Left Ventricular Ejection
    Fraction <50%.

    - Patients with previous history of acute cardiac failure.

    - Patients with previous history and/or unresolved corneal disorders.

    - Known intolerance to infused protein products or maytansinoids.

    - Patients treated with strong CYP3A inhibitors within 2 weeks prior study drug
    administration.

    - For patients to be treated in the midazolam cohort:

    - Any treatment known to induce CYP3A isoenzymes or to inhibit CYP3A4 activities not
    allowed within 2 weeks before midazolam administration and up to the end of
    pharmacokinetic sampling following the last midazolam administration.

    - Any contra-indications to midazolam, according to the applicable labeling.

    - Patients older than 60 years.

    The above information is not intended to contain all considerations relevant to a
    patient's potential participation in a clinical trial.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Dose Escalation to determine the maximum tolerated dose (MTD) of SAR566658

    Extension Cohorts to evaluate the preliminary anti-tumoral effect of SAR566658

    To assess the effect of SAR566658 at the recommended dose on CYP3A enzyme activity using midazolam as probe

    Secondary Outcome Measures

    Overall safety profile based on adverse events reporting, laboratory tests, vital signs and specific pulmonary and ocular tests, according to the NCI-CTC AE v4.03

    Pharmacokinetic (PK) parameters

    Immunogenicity evaluation (anti-drug antibodies)

    Antitumoral response

    To assess the effect of SAR566658 at recommended dose on CYP3A enzyme activity using midazolam

    To assess safety in the alternative schedules of SAR566658 administration

    Trial Keywords