Evaluation of SAR408701 in Japanese Patients With Advanced Malignant Solid Tumors
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| ClinicalTrials.gov Identifier: NCT03324113 |
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Recruitment Status :
Completed
First Posted : October 27, 2017
Last Update Posted : January 9, 2023
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Sponsor:
Sanofi
Information provided by (Responsible Party):
Sanofi
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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.
Secondary Objectives:
- To characterize the overall safety profile of SAR408701 monotherapy.
- To characterize the pharmacokinetic (PK) profile of SAR408701 and its metabolites.
- To evaluate the pharmacodynamic (PDy) effect of SAR408701 on levels of circulating carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) for main dose escalation part.
- 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 | Drug: SAR408701 Drug: dexamethasone Drug: naphazoline Drug: diphenhydramine | Phase 1 |
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) |
| Actual Enrollment : | 34 participants |
| Allocation: | N/A |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase I Study to Evaluate Safety and Pharmacokinetics of SAR408701 Administered Intravenously as Monotherapy in Japanese Patients With Advanced Malignant Solid Tumors |
| Actual Study Start Date : | October 17, 2017 |
| Actual Primary Completion Date : | November 18, 2022 |
| Actual Study Completion Date : | December 26, 2022 |
| Arm | Intervention/treatment |
|---|---|
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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
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Drug: SAR408701
Pharmaceutical form: solution for infusion Route of administration: intravenous Other Name: Tusamitamab ravtansine Drug: dexamethasone Pharmaceutical form: solution for eye drop Route of administration: eye drop Other Name: Santeson ophthalmic solution Drug: naphazoline Pharmaceutical form: solution for eye drop Route of administration: eye drop Other Name: Clearine Drug: diphenhydramine Pharmaceutical form: tablet Route of administration: oral Other Name: Restamin Kowa |
Primary Outcome Measures :
- IMP-related dose limiting toxicities (DLT) [ Time Frame: 4 weeks, Dose escalation q3w part: 3 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 :
- 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
- Maximum observed concentration (Cmax) of SAR408701 [ Time Frame: Main dose-escalation part: Cycle 1 and Cycle 4 (each cycle is 14 days); Dose-escalation bis part with loading dose: Cycle 1 (Cycle 1 is 14 days), Dose-escalation q3w part: Cycle 1 and Cycle2 day 1 (Cycle 1 is 21 days) ]Cmax for SAR408701 will be assessed after single and repeat doses, as relevant
- Cmax of DM4 and Me-DM4 [ Time Frame: Main dose-escalation part: Cycle 1 and Cycle 4 (each cycle is 14 days); Dose-escalation bis part with loading dose: Cycle 1 (Cycle 1 is 14 days), Dose-escalation q3w part: Cycle 1 and Cycle2 day 1 (Cycle 1 is 21 days) ]Cmax for DM4 and Me-DM4 will be assessed after single and repeat doses, as relevant
- Time to reach maximum concentration (Tmax) of SAR408701 [ Time Frame: Main dose-escalation part: Cycle 1 and Cycle 4 (each cycle is 14 days); Dose-escalation bis part with loading dose: Cycle 1 (Cycle 1 is 14 days), Dose-escalation q3w part: Cycle 1 and Cycle2 day 1 (Cycle 1 is 21 days) ]Tmax for SAR408701 will be assessed after single and repeat doses, as relevant
- Tmax of DM4 and Me-DM4 [ Time Frame: Main dose-escalation part: Cycle 1 and Cycle 4 (each cycle is 14 days); Dose-escalation bis part with loading dose: Cycle 1 (Cycle 1 is 14 days), Dose-escalation q3w part: Cycle 1 and Cycle2 day 1 (Cycle 1 is 21 days) ]Tmax for DM4 and Me-DM4 will be assessed after single and repeat doses, as relevant
- Area under the concentration-time curve (AUC) of SAR408701 [ Time Frame: Main dose-escalation part: Cycle 1 and Cycle 4 (each cycle is 14 days); Dose-escalation bis part with loading dose: Cycle 1 (Cycle 1 is 14 days), Dose-escalation q3w part: Cycle 1 and Cycle2 day 1 (Cycle 1 is 21 days) ]AUC of SAR408701 from time zero extrapolated to infinity
- AUC of DM4 and Me-DM4 [ Time Frame: Main dose-escalation part: Cycle 1 and Cycle 4 (each cycle is 14 days); Dose-escalation bis part with loading dose: Cycle 1 (Cycle 1 is 14 days), Dose-escalation q3w part: Cycle 1 and Cycle2 day 1 (Cycle 1 is 21 days) ]AUC of DM4 and Me-DM4 from time zero extrapolated to infinity
- Assessment of PDy effect [ Time Frame: Up to an average of 10 months ]Assessment of plasma CEACAM5 levels in main dose-escalation part
- 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
- Detection of anti-SAR408701 antibody [ Time Frame: Up to an average of 10 months ]Immunogenicity evaluation for anti-SAR408701 antibodies
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| Ages Eligible for Study: | 20 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion criteria:
- Locally advanced or metastatic solid malignant tumor disease for which, in the judgement of the investigator, no standard alternative therapy is available.
- Inclusion is likely to be expressing CEACAM5.
- At least 6 x 5 μm slides from formalin-fixed paraffin-embedded (FFPE) archival tissue should be available for retrospective central evaluation of CEACAM5 expression.
- Patient understands and has signed the Written Informed Consent form and is willing and able to comply with the requirements of the trial.
Exclusion criteria:
- Patient 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 patients of childbearing potential and male patients 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.
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
Locations
| Japan | |
| Investigational Site Number 3920003 | |
| Kashiwa-Shi, Japan | |
| Investigational Site Number 3920002 | |
| Nagoya-Shi, Japan | |
| Investigational Site Number 3920001 | |
| Sunto-Gun, Japan | |
Sponsors and Collaborators
Sanofi
Investigators
| Study Director: | Clinical Sciences & Operations | Sanofi |
| Responsible Party: | Sanofi |
| ClinicalTrials.gov Identifier: | NCT03324113 |
| Other Study ID Numbers: |
TCD15054 U1111-1191-5464 ( Other Identifier: UTN ) |
| First Posted: | October 27, 2017 Key Record Dates |
| Last Update Posted: | January 9, 2023 |
| Last Verified: | January 2023 |
| 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://vivli.org |
| 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:
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Neoplasms Diphenhydramine Promethazine Dexamethasone Naphazoline Ophthalmic Solutions 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 Antineoplastic Agents Pharmaceutical Solutions Sleep Aids, Pharmaceutical Hypnotics and Sedatives Central Nervous System Depressants Anesthetics, Local Anesthetics Sensory System Agents Histamine H1 Antagonists Histamine Antagonists Histamine Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Anti-Allergic Agents |