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

This study is currently recruiting participants.
Verified April 2014 by Sanofi
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01156870
First received: July 2, 2010
Last updated: April 14, 2014
Last verified: April 2014
  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

Condition Intervention Phase
Neoplasm Malignant
Drug: SAR566658
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Dose Escalation To determine the maximum tolerated dose (MTD) of SAR566658 [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]
  • Extension Cohorts To evaluate the preliminary anti-tumoral effect of SAR566658 [ Time Frame: Anticancer activity is assessed every 6 weeks ] [ Designated as safety issue: No ]
  • To assess the effect of SAR566658 at the recommended dose on CYP3A enzyme activity using midazolam as probe [ Time Frame: At D1 and D4 of administration of SAR566658 for 24h of midazolam dosing ] [ Designated as safety issue: No ]

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 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic (PK) parameters [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Immunogenicity evaluation (anti-drug antibodies) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Antitumoral response [ Time Frame: Up to treatment discontinuation ] [ Designated as safety issue: No ]
  • To assess the effect of SAR566658 at recommended dose on CYP3A enzyme activity using midazolam [ Time Frame: Up to Cycle 2 ] [ Designated as safety issue: No ]
  • To assess safety in the alternative schedules of SAR566658 administration [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 150
Study Start Date: September 2010
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SAR566658
SAR566658 will be administered by intravenous (IV) infusion according to three different schedules
Drug: SAR566658

Pharmaceutical form:solution for infusion

Route of administration: intravenous


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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

Diagnosis of CA6-positive solid tumors as moderate to intense membrane staining of ≥30% 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 25% compared to theoretical baseline pulmonary volumes and theoretical baseline Diffusing capacity of the Lung for Carbon monoxide
  • 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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01156870

Contacts
Contact: For site information, send an email with site number to Contact-Us@sanofi.com

Locations
United States, Ohio
Investigational Site Number 840002 Recruiting
Cincinnati, Ohio, United States, 45267-0542
United States, Texas
Investigational Site Number 840001 Recruiting
San Antonio, Texas, United States, 78229
France
Investigational Site Number 250001 Recruiting
Toulouse Cedex, France, 31052
Spain
Investigational Site Number 724001 Recruiting
Madrid, Spain, 28050
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01156870     History of Changes
Other Study ID Numbers: TED10499, U1111-1116-4129, 2011-003891-35
Study First Received: July 2, 2010
Last Updated: April 14, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on April 14, 2014