A Safety and Efficacy Study of SAR405838 and Pimasertib in Cancer Patients

NCT01985191 | Completed Phase 1

• 3 other identifiers: TCD133882013-002325-33U1111-1144-8349
• Study Type: interventional
• Target: 26
• Locations: 2 countries
• Sites: 4

Brief Summary

Primary Objectives: To determine the recommended Phase 2 dose of SAR405838 / pimasertib combination therapy in patients with solid tumors. To assess the anti-tumor activities of SAR405838 / pimasertib in patients with solid tumors. Secondary Objectives: To characterize the pharmacokinetic profile of SAR405838 and pimasertib. To evaluate the pharmacodynamic effect of the SAR405838 and pimasertib. To characterize genetic status in tumor tissue and circulating tumor DNA.

Conditions

Neoplasm Malignant

Outcome Measures

Primary Outcomes (2)

• SAR405838 (pimasertib) RP2D assessed by dose-limiting toxicities and pharmacological activities

  6 weeks for each patient at each dose level

• Changes of tumor dimension by imaging

  At least 3 months for each patient

Secondary Outcomes (7)

• Overall safety profile of SAR405838 (pimasertib), number of participants with adverse events

  Throughout the study

• Pharmacokinetic parameters for both SAR405838 (pimasertib): the maximum concentration in blood (Cmax)

  3 months for each patient

• Pharmacokinetic parameters for both SAR405838 (pimasertib): time to the maximum concentration (Tmax)

  3 months for each patient

• Pharmacokinetic parameters for both SAR405838 (pimasertib): area under the curve (AUC), etc.

  3 months for each patient

• Biomarker changes in response to SAR405838 (pimasertib) treatment

  3 months for each patient

Study Arms (1)

Arm 1

EXPERIMENTAL

SAR405838 and pimasertib in escalating doses

Drug: SAR405838; Drug: Pimasertib

Interventions

SAR405838 DRUG

Pharmaceutical form:capsule Route of administration: oral

Arm 1

Pimasertib DRUG

Pharmaceutical form: capsule Route of administration: oral

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed diagnosis of a solid tumor.
• Presence of locally advanced or metastatic disease with at least one measurable lesion.
• Ability to provide written informed consent. Evidence of a personally signed informed consent.

You may not qualify if:

• Age \<18 years.
• Eastern Cooperative Oncology Group performance status of \>1.
• Inadequate functions of bone marrow, liver, and kidney.
• Positive pregnancy test in women of child-bearing potential.
• Pregnancy or breast-feeding.
• Extensive prior radiotherapy.
• The patient has retinal degenerative disease, history of uveitis, or history of retinal vein occlusion, or history of retinal detachment, or has medically relevant abnormalities identified on screening ophthalmologic examination.
• Prior history of myositis or rhabdomyolysis.
• Recent major surgery or trauma, unhealing/open wounds.
• The patient has had congestive heart failure, unstable angina, a myocardial infarction, cardiac conduction abnormality or pacemaker or a stroke within 3 months of entering the study.
• The patient has a baseline corrected QT interval (QTc) \>480 ms or left ventricular ejection fraction (LVEF) \<50% or less than the lower limit of normal.
• The patient has a previously-identified allergy or hypersensitivity to components of the study treatment formulations.
• Unwillingness or inability to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
• Unwillingness, if not postmenopausal or surgically sterile, to abstain from sexual intercourse or employ an effective barrier or medical method of contraception during the study drug administration and follow-up periods.
• Recent history of acute pancreatitis.

Sponsors & Collaborators

• Sanofi: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (4)

Investigational Site Number 250001

Villejuif, 94805, France

Location

Investigational Site Number 528001

Amsterdam, 1066 CX, Netherlands

Location

Investigational Site Number 528003

Rotterdam, 3075 EA, Netherlands

Location

Investigational Site Number 528002

Utrecht, 3584 CX, Netherlands

Location

Related Publications (1)

• de Weger VA, de Jonge M, Langenberg MHG, Schellens JHM, Lolkema M, Varga A, Demers B, Thomas K, Hsu K, Tuffal G, Goodstal S, Mace S, Deutsch E. A phase I study of the HDM2 antagonist SAR405838 combined with the MEK inhibitor pimasertib in patients with advanced solid tumours. Br J Cancer. 2019 Feb;120(3):286-293. doi: 10.1038/s41416-018-0355-8. Epub 2018 Dec 26.

  PMID: 30585255 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

SAR405838; N-(2,3-dihydroxypropyl)-1-((2-fluoro-4-iodophenyl)amino)isonicotinamide

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2013
• First Posted: November 15, 2013
• Study Start: November 1, 2013
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: February 25, 2016

Record last verified: 2016-02

Locations

NL (3); FR (1)