Japanese Phase 1 Trial of Sym004 in Solid Tumors

Solid Tumors Clinical Trial

Official title:

A Japanese Phase I Open-label Dose-escalation Trial of Sym004 Administered as Monotherapy in Japanese Subjects With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01955473
• Other study ID #: EMR 200637-001
• Status: Completed
• Phase: Phase 1
• First received: September 27, 2013
• Last updated: July 28, 2016
• Start date: October 2013
• Est. completion date: October 2015

Study information

• Verified date: July 2016
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial Summary

This is a Phase 1, open-label, dose-escalation trial to assess the safety and tolerability of Sym004, administered weekly or biweekly as monotherapy in Japanese subjects with advanced solid tumors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Japanese male or female subjects aged greater than or equal to 20 years at the time of informed consent signature

• Histologically or cytologically confirmed cancer

• Refractory or recurrent advanced late stage solid tumors without available therapeutic options which are likely to provide patient benefit (failure and/or intolerance to standard anti-cancer therapy)

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Life expectancy of at least 3 months

• Written informed consent given before any trial-related activities are carried out

• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• Subjects with symptomatic brain metastases

• Subjects who received total resection or irradiation of the target lesion

• Received any of the following medications within 4 weeks before the first administration of Sym004 at Week 1: cytotoxic or cytostatic anti-cancer therapy, antibody therapy, tyrosine kinase inhibitors, and any investigational agent

• Received vaccine therapy as anticancer treatment within 12 weeks before the first administration of Sym004 at Week 1

• Diarrhea of greater than Grade 1 according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 (v4.03)

• Skin manifestation of greater than Grade 1 according to NCI-CTCAE (v4.03)

• Magnesium of less than 0.9 milligram per deciliter (mg/dL)

• Abnormal organ or bone marrow function as defined in the protocol

• Received immunosuppressive agents (including systemic corticosteroids used at doses above 20 milligram per day (mg/day) of prednisolone or equivalent) within 4 weeks before the first administration of Sym004 at Week 1

• Active severe infection, any other concurrent disease or medical conditions that are deemed to interfere with the conduct of the trial as judged by the Investigator

• Known human immunodeficiency virus (HIV) positive, active Hepatitis B or C, or uncontrolled allergic conditions or allergy to Sym004 or its components

• Clinically significant cardiac disease or concurrent, uncontrolled medical condition

• Known previous Grade 3 to 4 infusion-related reactions, according to NCI-CTCAE (v4.03), with chimeric monoclonal antibodies

• Other protocol defined exclusion criteria could apply

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Solid Tumors

Intervention

Drug:
• Sym004
Part-A (dose-escalation): Sym004 will be administered intravenously either weekly at 6 to 12 milligram per kilogram (mg/kg) or biweekly at 18 mg/kg from Week 1 until unacceptable toxicity, disease progression, or consent withdrawal. Part-B (dose-expansion): After the maximum tolerated dose (MTD) is determined in Part-A, up to 30 additional subjects will continue to receive treatment in Part-B.

Locations

Country	Name	City	State
Germany	Please contact the Merck KGaA Communication Center located in	Darmstadt

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicity as determined in Part-A		Up to Week 4	Yes
Primary	Number of subjects with Adverse Events		Up to 4 weeks after the last Sym004 administration	Yes
Secondary	Pharmacokinetic profile of Sym004: Area under curve (AUC), Half-life (t1/2 ), Clearance (CL), Volume of distribution at the elimination phase (Vz ), Maximum concentration (Cmax ), Trough concentration (Ctrough), Time to reach Cmax (tmax )		Up to 8 weeks after the last Sym004 administration	No
Secondary	Best overall response rate		Week 7 and thereafter every 6 weeks, up to 4 weeks after the last Sym004 administration	No
Secondary	Duration of overall response		Week 7 and thereafter every 6 weeks until the first date of objectively documented recurrent or progressive disease, up to 4 weeks after the last Sym004 administration	No
Secondary	Disease control rate		Week 7 and thereafter every 6 weeks, up to 4 weeks after the last Sym004 administration	No
Secondary	Duration of disease control		Week 7 and thereafter every 6 weeks until the first date of objectively documented recurrent or progressive disease, up to 4 weeks after the last Sym004 administration	No
Secondary	Time to progression		Time from enrollment until the date of objectively documented disease progression, up to 4 weeks after the last Sym004 administration	No
Secondary	Progression-free survival time		Time from enrollment until the date of objectively documented disease progression or death, up to 4 weeks after the last Sym004 administration	No
Secondary	Change from Baseline in anti-drug antibody (ADA) titer at Weeks 1 and 5		Baseline, Weeks 1 and 5	No
Secondary	Epidermal growth factor receptor levels in skin tissues		Weeks 1 and 5	No