ClinicalTrials.gov
ClinicalTrials.gov Menu

Evaluation of SAR408701 in Combination With Other Anti-tumor Drug in Japanese Patients With Advanced Malignant Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03324113
Recruitment Status : Recruiting
First Posted : October 27, 2017
Last Update Posted : April 12, 2018
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

Primary Objective:

  • To evaluate tolerability and safety of SAR408701 when administered as a single agent according to the investigational medicinal product (IMP) related dose limiting toxicities (DLTs) to determine the recommended dose (RD) of SAR408701 in Japanese patients with advanced malignant solid tumors (dose-escalation part).
  • To evaluate tolerability and safety of SAR408701 in combination with other anti-tumor drug according to the IMP related DLTs to determine RD of SAR408701 in Japanese patients with locally advanced or metastatic colorectal cancer (CRC) (combination part).

Secondary Objectives:

  • To characterize the overall safety profile of SAR408701 monotherapy and in combination with other anti-tumor drug.
  • To characterize the pharmacokinetic (PK) profile of SAR408701 and its metabolites, and TAS-102 components (trifluridine and tipiracil).
  • To evaluate the pharmacodynamic (PDy) effect of SAR408701 on levels of circulating carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5).
  • To assess preliminary efficacy according to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 criteria and other indicators of antitumor activity.
  • To assess the potential immunogenicity of SAR408701.

Condition or disease Intervention/treatment Phase
Neoplasm Malignant Biological: SAR408701 Drug: trifluridine and tipiracil TAS-102 Drug: naphazoline Drug: dexamethasone Drug: diphenhydramine Phase 1

Detailed Description:
The study duration per participant 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 (EOT) visit around 30 days after the last administration of IMP, and at least one follow-up (FU) visit after the EOT visit.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/Ib Study to Evaluate Safety and Pharmacokinetics of SAR408701 Administered Intravenously as Monotherapy and in Combination With Other Anti-tumor Drug in Japanese Patients With Advanced Malignant Solid Tumors
Actual Study Start Date : October 17, 2017
Estimated Primary Completion Date : December 10, 2019
Estimated Study Completion Date : December 10, 2019

Arm Intervention/treatment
Experimental: SAR408701 Monotherapy
SAR408701 Dose escalation administered as a single agent intravenously, on Day 1 and once every two weeks, to patients with malignant solid tumors
Biological: SAR408701

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Drug: naphazoline

Pharmaceutical form: solution for eye drop

Route of administration: eye drop

Other Name: Clearine
Drug: dexamethasone

Pharmaceutical form: solution for eye drop

Route of administration: eye drop

Other Name: Santeson ophthalmic solution
Drug: diphenhydramine

Pharmaceutical form: tablet

Route of administration: oral

Other Name: Restamin Kowa
Experimental: SAR408701 + TAS-102 Combination
SAR408701 administered intravenously at the maximum tolerated dose (MTD), once every two weeks in combination with TAS-102 given orally to patients with colorectal cancer
Biological: SAR408701

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Drug: trifluridine and tipiracil TAS-102

Pharmaceutical form: tablet

Route of administration: oral

Other Name: Lonsurf
Drug: naphazoline

Pharmaceutical form: solution for eye drop

Route of administration: eye drop

Other Name: Clearine
Drug: dexamethasone

Pharmaceutical form: solution for eye drop

Route of administration: eye drop

Other Name: Santeson ophthalmic solution
Drug: diphenhydramine

Pharmaceutical form: tablet

Route of administration: oral

Other Name: Restamin Kowa



Primary Outcome Measures :
  1. IMP-related dose limiting toxicities (DLT) [ Time Frame: Phase 1 monotherapy - 4 weeks; Phase 1b combination - 4 weeks ]
    IMP-related DLTs are defined as adverse events (AE) related to the IMPs in absence of clear evidence to the contrary, after validation by the Study Committee, and if not related to a disease progression, graded using National Cancer Institute common Toxicity Criteria (NCI-CTC) scale v4.03


Secondary Outcome Measures :
  1. Treatment emergent adverse events [ Time Frame: Up to an average of 9 months ]
    Overall safety profile characterized in terms of the type, frequency, severity, seriousness, and relationship to study therapy of any AEs based on standard and systematic assessment including physical findings, laboratory tests or other investigations

  2. Maximum concentration (Cmax) of SAR408701 [ Time Frame: Phase 1 monotherapy - Cycle 1 and Cycle 4 (each cycle is 14 days); Phase 1b combination - Cycle 1 (Cycle 1 is 28 days) ]
    Cmax for SAR408701 will be assessed after single and repeat doses, as relevant

  3. Cmax of maytansinoid derivative 4 (DM4) and Me-DM4 [ Time Frame: Phase 1 monotherapy - Cycle 1 and Cycle 4 (each cycle is 14 days); Phase 1b combination - Cycle 1 (Cycle 1 is 28 days) ]
    Cmax for DM4 and Me-DM4 will be assessed after single and repeat doses, as relevant

  4. Cmax of trifluridine and tipiracil [ Time Frame: Phase 1b combination - Cycle 1 (Cycle 1 is 28 days) ]
    Cmax for trifluridine and tipiracil will be assessed after single and repeat doses, as relevant

  5. Time to reach maximum concentration (Tmax) of SAR408701 [ Time Frame: Phase 1 monotherapy - Cycle 1 and Cycle 4 (each cycle is 14 days); Phase 1b combination - Cycle 1 (Cycle 1 is 28 days) ]
    Tmax for SAR408701 will be assessed after single and repeat doses, as relevant

  6. Tmax of DM4 and Me-DM4 [ Time Frame: Phase 1 monotherapy - Cycle 1 and Cycle 4 (each cycle is 14 days); Phase 1b combination - Cycle 1 (Cycle 1 is 28 days) ]
    Tmax for DM4 and Me-DM4 will be assessed after single and repeat doses, as relevant

  7. Tmax of trifluridine and tipiracil [ Time Frame: Phase 1b combination - Cycle 1 (Cycle 1 is 28 days) ]
    Tmax for trifluridine and tipiracil will be assessed after single and repeat doses, as relevant

  8. Area Under the Plasma Concentration versus time curve (AUC) of SAR408701 [ Time Frame: Phase 1 monotherapy - Cycle 1 and Cycle 4 (each cycle is 14 days); Phase 1b combination - Cycle 1 (Cycle 1 is 28 days) ]
    AUC of SAR408701 from time zero extrapolated to infinity

  9. AUC of DM4 and Me-DM4 [ Time Frame: Phase 1 monotherapy - Cycle 1 and Cycle 4 (each cycle is 14 days); Phase 1b combination - Cycle 1 (Cycle 1 is 28 days) ]
    AUC of DM4 and Me-DM4 from time zero extrapolated to infinity

  10. AUC0-10hr of trifluridine and tipiracil [ Time Frame: Phase 1b combination - Cycle 1 (Cycle 1 is 28 days) ]
    AUC of trifluridine and tipiracil from time zero to 10 hours after dosing

  11. Assessment of PDy effect [ Time Frame: Up to an average of 10 months ]
    Assessment of plasma CEACAM5 levels

  12. Assessment of anti-tumor activity [ Time Frame: Up to an average of 10 months ]
    Assessment of tumor response using standard imaging, as defined by RECIST 1.1 criteria

  13. Detection of anti-SAR408701 antibody [ Time Frame: Up to an average of 10 months ]
    Immunogenicity evaluation for anti-SAR408701 antibodies



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   20 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • For participants to the Phase 1 Monotherapy part: Locally advanced or metastatic solid malignant tumor disease for which, in the judgement of the investigator, no standard alternative therapy is available.
  • For participants to the Phase 1b Combination part: Diagnosis of locally advanced or metastatic CRC which has been previously treated with more than 2 regimens for the following treatment: fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an angiogenesis inhibitor therapy, and an anti-epidermal growth factor receptor therapy (if RAS wild-type tumor) and is appropriate for TAS-102 therapy.
  • At least 6 x 5 μm slides from formalin-fixed paraffin-embedded (FFPE) archival tissue should be available for retrospective central evaluation of tumor carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) expression.
  • Participant understands and has signed the Written Informed Consent form and is willing and able to comply with the requirements of the trial.

Exclusion criteria:

  • Participant less than 20 years old.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2.
  • Life expectancy <12 weeks.
  • Known or symptomatic brain metastasis (other than totally resected or previously irradiated and non-progressive/relapsing) or lepto-meningeal carcinomatosis.
  • Female participants of childbearing potential and male participants with female partners of childbearing potential who do not agree to use accepted and effective method of contraception during the study treatment period and for 6 months following discontinuation of IMP.
  • Significant concomitant illnesses, including all severe medical conditions which, in the opinion of the Investigator or Sponsor, would impair the patient's participation in the study or interpretation of the results.
  • Prior therapy targeting CEACAM5.
  • Prior maytansinoid treatments (maytansinoid derivative 1 [DM1] or maytansinoid derivative 4 [DM4] antibody drug conjugates).
  • Previous history and or unresolved corneal disorders.
  • Medical conditions requiring concomitant administration of medications with narrow therapeutic window, metabolized by cytochrome P450 (CYP) 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 first administration of SAR408701.
  • For participants to the Combination part only: Prior TAS-102 treatment.

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03324113


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

Locations
Japan
Investigational Site Number 3920003 Recruiting
Kashiwa-Shi, Japan
Investigational Site Number 3920002 Recruiting
Nagoya-Shi, Japan
Investigational Site Number 3920001 Recruiting
Sunto-Gun, Japan
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT03324113     History of Changes
Other Study ID Numbers: TCD15054
U1111-1191-5464 ( Other Identifier: UTN )
First Posted: October 27, 2017    Key Record Dates
Last Update Posted: April 12, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/
URL: http://

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Neoplasms
Pharmaceutical Solutions
Dexamethasone
Diphenhydramine
Antineoplastic Agents
Ophthalmic Solutions
Promethazine
Naphazoline
Trifluridine
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Sensory System Agents
Histamine H1 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Hypnotics and Sedatives
Anti-Allergic Agents