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

• ClinicalTrials.gov Identifier: NCT01156870
• Recruitment Status: Completed
• First Posted: July 5, 2010
• Last Update Posted: May 10, 2017
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Neoplasm Malignant	Drug: SAR566658	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 114 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Actual Study Start Date: September 8, 2010
• Actual Primary Completion Date: April 7, 2017
• Actual Study Completion Date: April 7, 2017

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Dose Escalation to determine the maximum tolerated dose (MTD) of SAR566658 [ Time Frame: 3 weeks ]
2. Extension Cohorts to evaluate the preliminary anti-tumoral effect of SAR566658 [ Time Frame: Anticancer activity is assessed every 6 weeks ]
3. 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 ]

Secondary Outcome Measures :

1. 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 ]
2. Pharmacokinetic (PK) parameters [ Time Frame: Up to 2 years ]
3. Immunogenicity evaluation (anti-drug antibodies) [ Time Frame: Up to 2 years ]
4. Antitumoral response [ Time Frame: Up to treatment discontinuation ]
5. To assess the effect of SAR566658 at recommended dose on CYP3A enzyme activity using midazolam [ Time Frame: Up to Cycle 2 ]
6. To assess safety in the alternative schedules of SAR566658 administration [ Time Frame: Up to 2 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Ohio

Investigational Site Number 840002

Cincinnati, Ohio, United States, 45267-0542

United States, Texas

Investigational Site Number 840001

San Antonio, Texas, United States, 78229

France

Investigational Site Number 250001

Toulouse Cedex, France, 31052

Spain

Investigational Site Number 724002

Madrid, Spain, 28040

Investigational Site Number 724001

Madrid, Spain, 28050

Sponsors and Collaborators

Sanofi

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT01156870
• Other Study ID Numbers: TED10499; U1111-1116-4129 ( Other Identifier: UTN )
• First Posted: July 5, 2010
• Last Update Posted: May 10, 2017
• Last Verified: May 2017

Additional relevant MeSH terms:

Neoplasms