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Evaluation of SAR408701 in Patients With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT02187848
Recruitment Status : Active, not recruiting
First Posted : July 11, 2014
Last Update Posted : March 26, 2021
Sponsor:
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE June 24, 2014
First Posted Date  ICMJE July 11, 2014
Last Update Posted Date March 26, 2021
Actual Study Start Date  ICMJE July 23, 2014
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 23, 2019)
  • Number of dose limiting adverse events (every 2 week cycle) [ Time Frame: 4 weeks ]
  • Assessment of overall response rate using standard imaging and RECIST 1.1 criteria [ Time Frame: Up to 40 months ]
  • Number of dose limiting adverse events (every 3 week cycle) [ Time Frame: 3 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 8, 2014)
  • Number of dose limiting adverse events [ Time Frame: 4 weeks ]
  • Assessment of overall response rate using standard imaging and RECIST 1.1 criteria [ Time Frame: Up to 30 months - assessment every 8 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 23, 2019)
  • Number of treatment emergent adverse events [ Time Frame: Up to 4 years ]
  • Maximum concentration (Cmax) [ Time Frame: 2 months ]
  • Time to reach maximum concentration (tmax) [ Time Frame: 2 months ]
  • Trough plasma concentrations (Ctrough) [ Time Frame: Intensive testing within first 2 months, then every 2 weeks ]
  • Area under the plasma concentration versus time curve between 0 and 14 days (AUC0-14day) for Q2W or between 0 and 21 days (AUC-21 day) for Q3W [ Time Frame: 2 months ]
  • Mean systemic clearance (CL) [ Time Frame: 2 months ]
  • Clearance at steady state (CLss) [ Time Frame: 2 months ]
  • Accumulation ratio (Rac) on AUC0-14day and Cmax [ Time Frame: 2 months ]
  • Detection of the development of anti-SAR408701 antibody [ Time Frame: Up to 40 months ]
  • Duration of response [ Time Frame: Up to 40 months - assessment every 6-8 weeks ]
  • Time to Progression [ Time Frame: Up to 40 months - assessment every 6-8 weeks ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 8, 2014)
  • Number of treatment emergent adverse events [ Time Frame: Up to 3 years ]
  • Maximum concentration (Cmax) [ Time Frame: 2 months ]
  • Time to reach maximum concentration (tmax) [ Time Frame: 2 months ]
  • Trough plasma concentrations (Ctrough) [ Time Frame: Intensive testing within first 2 months, then every 2 weeks ]
  • Area under the plasma concentration curve versus time curve between 0 and 14 days (AUC0-14day) [ Time Frame: 2 months ]
  • Mean systemic clearance (CL) [ Time Frame: 2 months ]
  • Clearance at steady state (CLss) [ Time Frame: 2 months ]
  • Accumulation ratio (Rac) on AUC0-14day and Cmax [ Time Frame: 2 months ]
  • Detection of the development of anti-SAR408701 antibody [ Time Frame: Every 2 weeks for 4 weeks, then every 4 weeks until first follow-up, then every 3 months only if positive, for up to one year ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of SAR408701 in Patients With Advanced Solid Tumors
Official Title  ICMJE A First-in-Human Study for the Evaluation of the Safety, Pharmacokinetics and Antitumor Activity of SAR408701 in Patients With Advanced Solid Tumors
Brief Summary

Primary Objectives:

  • To determine the maximum tolerated dose (MTD) of SAR408701 administered as monotherapy, once every 2 weeks (with and without a loading dose at Cycle 1) to patients with advanced solid tumors (Main Escalation and Loading Dose Escalation Q2W).
  • To determine the maximum tolerated dose (MTD) of SAR408701 administered as monotherapy, once every 3 weeks to patients with advanced solid tumors (Escalation Q3W Cycle).
  • To assess efficacy according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) (Expansion Phase) when SAR408701 is administered once every 2 weeks with or without a loading dose at Cycle 1.

Secondary Objectives:

  • To characterize the overall safety profile of SAR408701.
  • To characterize the pharmacokinetic (PK) profile of SAR408701 and of its potential circulating derivatives.
  • To identify the recommended phase 2 dose (RP2D) of SAR408701.
  • To assess the potential immunogenicity of SAR408701.
Detailed Description The study duration for an individual patient will start from the signature of the informed consent, will include a period to assess eligibility (screening period) of up to approximately 4 weeks (28 days), a treatment period and an end-of-treatment visit around 30 days following the last administration of study drug, and at least one follow-up visit after the end-of-treatment visit. Additional follow-up visits may be required until resolution or stabilization of adverse events (at least 30 days). Treatment may continue until precluded by toxicity, progression, or upon patient's request. If the patient stops study treatment for reason other than disease progression, follow-up visit will be performed every 3 months until disease progression or initiation of another anti-tumor treatment or death, whichever comes first.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neoplasm Malignant
Intervention  ICMJE Drug: SAR408701
Pharmaceutical form: concentrate for solution for infusion Route of administration: intravenous
Study Arms  ICMJE
  • Experimental: SAR408701 Main Dose Escalation Cohort
    Dose escalation administered intravenously, once every two weeks
    Intervention: Drug: SAR408701
  • Experimental: SAR408701 Expansion Cohort colorectal cancer (CRC)
    Administered intravenously at the maximum tolerated dose (MTD), once every 2 weeks, to patients with colorectal cancer
    Intervention: Drug: SAR408701
  • Experimental: SAR408701 Expansion Cohort non-squamous NSCLC
    Administered intravenously at the MTD, once every 2 weeks, to patients with carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) expressing non-squamous non-small cell lung cancer (NSCLC) of at least 50% of tumor cells at or above 2+ intensity
    Intervention: Drug: SAR408701
  • Experimental: SAR408701 Expansion Cohort gastric adenocarcinoma
    Administered intravenously at the MTD, once every 2 weeks, to patients with CEACAM5 expressing gastric adenocarcinoma
    Intervention: Drug: SAR408701
  • Experimental: SAR408701 Loading Dose Escalation cohorts (Escalation bis)
    Loading dose escalation administered intravenously at first cycle, followed by MTD, once every 2 weeks
    Intervention: Drug: SAR408701
  • Experimental: SAR408701 Expansion Cohort non-squamous NSCLC (Lung bis)
    Administered intravenously at the MTD, once every 2 weeks, to patients with CEACAM5 expressing non-squamous NSCLC of at least 1% but below 50% of tumor cells at or above 2+ intensity
    Intervention: Drug: SAR408701
  • Experimental: SAR408701 Expansion Cohort colorectal cancer (CRC-L)
    Loading dose of determined MTD-L administered intravenously at first cycle, followed by MTD, once every 2 weeks
    Intervention: Drug: SAR408701
  • Experimental: SAR408701 Expansion Cohort small cell lung cancer (SCLC)
    Administered intravenously at the MTD, once every 2 weeks, to patients with CEACAM5 expressing SCLC
    Intervention: Drug: SAR408701
  • Experimental: SAR408701 Dose Escalation every 3 weeks cohort
    Dose escalation administered intravenously, once every three weeks
    Intervention: Drug: SAR408701
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: April 29, 2020)
313
Original Estimated Enrollment  ICMJE
 (submitted: July 8, 2014)
120
Estimated Study Completion Date  ICMJE September 2021
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  • Locally advanced or metastatic solid malignant tumor disease for which no standard alternative therapy is available.
  • Availability of archived tumor tissue for carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5 or CEA) testing.
  • For participants in the Dose Escalation Cohorts (Main Escalation and Loading Dose Cohorts at every 2 week cycle and Dose Escalation every 3 week cycle): patients with tumors expressing or likely to be expressing CEACAM5 which includes colorectal cancer (CRC), non-squamous non-small cell lung cancer (NSCLC), gastric adenocarcinoma, squamous cell carcinoma of the cervix, pancreas adenocarcinoma, bladder transitional cell carcinoma, cholangiocarcinoma, epithelial ovarian cancer and endometrial adenocarcinoma are favored, or if carcinoembryonic antigen (CEA) plasma levels >5 ng/mL.
  • For participants to the Expansion Phase cohorts: patients with CRC or with CEACAM5 positive non-squamous NSCLC, small cell lung cancer (SCLC) or gastric carcinoma (including esophago-gastric junction adenocarcinoma of the Siewert types II and III).
  • At least one measurable lesion by RECIST v1.1 in the Expansion Phase only.
  • At least one lesion amenable to biopsy (Expansion cohort - CRC and gastric cancer only). Patient must consent to a baseline biopsy for retrospective confirmation of tumor CEACAM5 expression, except if NSCLC or SCLC without lesion amenable to biopsy.
  • Signed informed consent.

Exclusion criteria:

  • Aged less than 18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status more than 1.
  • New or progressing brain involvement.
  • Concurrent treatment with any other anticancer therapy or inadequate wash-out period for prior anticancer therapies before first administration of SAR408701, or non-resolution of toxicities induced by these anticancer therapies.
  • Female or male patients with reproductive potential who do not agree to use an accepted effective method of contraception during the study treatment period and for at least 3 months following completion of study treatment.
  • Pregnancy or breast-feeding.
  • Participation to any clinical research study evaluating another investigational drug or therapy within 3 weeks of initiation of study regimen.
  • Prior therapy targeting CEACAM5.
  • Prior maytansinoid treatments (DM1 or DM4 antibody drug conjugates).
  • Poor bone marrow reserve resulting in low blood cell counts.
  • Poor kidney and liver functions.
  • Any of the following within 6 months prior to study enrolment: infectious or inflammatory bowel disease, diverticulitis, gastrointestinal perforation, intestinal obstruction, and gastrointestinal hemorrhage. Patients with malabsorption syndrome are excluded.
  • Previous history and or unresolved corneal disorders. The use of contact lenses is not permitted.
  • Unresolved signs and symptoms of neuropathy; Grade 1 is acceptable if prior neurotoxic drugs such as cisplatin or taxanes.
  • Abnormal cardiac function defined by a left ventricular ejection fraction (LVEF) of <50%.
  • Cardiac conduction defects, or any other clinically significant arrhythmias.
  • Known intolerance to infused protein products.
  • Medical conditions requiring concomitant administration of medications with narrow therapeutic window, metabolized by cytochrome P450 (CYPs) enzymes and for which a dose reduction cannot be considered.
  • Medical conditions requiring concomitant administration of strong CYP3A inhibitor, unless it can be discontinued at least 2 weeks before 1st administration of SAR408701.
  • Contraindications to the use of ophthalmic vasoconstrictor and/or corticosteroid as per package insert of each drug, including the following: increase intraocular pressure, prior or current glaucoma, narrow-angle glaucoma, ongoing eye infection, uncontrolled hypertension, known/suspected allergy to constituents of the preparation (such as sodium bisulfite).

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   France,   Korea, Republic of,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02187848
Other Study ID Numbers  ICMJE TED13751
2014-001130-29 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Individual participant data (IPD) and supporting clinical documents are available for request at clinicalstudydatarequest.com. While making information available we continue to protect the privacy of the participants in our clinical trials and to remove commercially confidential information (CCI). Details on Data Sharing criteria and process for requesting access can be found at this web address: clinicalstudydatarequest.com
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP