Open Label, Dose Escalation Trial of Oral Eg5 Kinesin-spindle Inhibitor 4SC-205 in Patients With Advanced Malignancies (AEGIS)

Open Label, Dose Escalation Trial of Oral 4SC-205 in Patients With Advanced Malignancies: First-In-Man Study of a Newly Developed, Oral Inhibitor of Kinesin-spindle Protein, Eg5

The purpose of the study is to investigate safety and tolerability of repeated ascending oral doses of 4SC-205 in patients with advanced and incurable solid tumors or malignant lymphomas.

Study Overview

• Status: Completed
• Conditions: Malignant Lymphomas; Advanced and Incurable Solid Tumors
• Intervention / Treatment: Drug: 4SC-205

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Essen, Germany
    • Universitätsklinikum Essen
  • Freiburg, Germany
    • Klinik für Tumorbiologie an der Albert-Ludwigs-Universität Freiburg (KTB)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

• One or more evaluable target lesion according to RECIST (by CT-scan, MRI or calipers), of which at least one evaluable target lesion (proven by CT or MRI) has to be located in the lung.
• Progressive disease as defined by new or progressive lesions on CT-scan, MRI, bone scan or by increase of PSA.
• Histologically or cytologically documented diagnosis of primary or metastatic solid tumors or malignant lymphomas refractory to prior standard therapy or for which no standard therapy exists. Entry will include, but is not limited to patients with prostate and breast cancer refractory to hormone treatment, ovarian cancer, head and neck cancer, non-small cell lung cancer, bladder cancer, colorectal cancer, kidney cancer, malignant melanoma or malignant lymphoma. Patients who have refused standard therapies are also eligible.
• ECOG Performance Status 0-2.
• Acceptable liver, renal and bone marrow function.

Main Exclusion Criteria:

• Prior treatment with other EG5 inhibitors.
• Antineoplastic therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within the last 2 weeks or a longer period depending on the defined characteristics of the agents used (e.g. 6 weeks for mitomycin C or nitrosourea). Patients must have recovered from any treatment-related toxicity (except for alopecia, fatigue and grade 1 neurotoxicity) prior to registration.
• Patients with a history of other malignancies unless having undergone definitive treatment more than 5 years prior to entry into the study and without evidence of recurrent malignant disease, excluding patients with basal cell carcinoma of the skin; superficial carcinoma of the bladder; carcinoma of the prostate with a current PSA < 0.1 ng/ml; or cervical intraepithelial neoplasia.
• Patients with a history of significant cardiovascular, neurological, endocrine, gastrointestinal, respiratory or inflammatory illness.
• Patients with a history of, who were treated for, or who are suspected of having, hepatitis B, hepatitis C or HIV.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 4SC-205	Drug: 4SC-205; Repeated ascending oral doses of 4SC-205.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of repeated ascending oral doses of 4SC-205. Determination of the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT).	6 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics	6 weeks
Anti-cancer activity of 4SC-205 after 6 weeks of treatment.	6 weeks
Effects of EG5 inhibition on biomarker modulation.	6 weeks

Collaborators and Investigators

• Sponsor: 4SC AG
• Investigators: Principal Investigator: Klaus Mross, PD Dr. med., Klinik für Tumorbiologie an der Albert-Ludwigs-Universität Freiburg (KTB)

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (ACTUAL): April 1, 2015
• Study Completion (ACTUAL): April 1, 2015

Study Registration Dates

• First Submitted: February 5, 2010
• First Submitted That Met QC Criteria: February 8, 2010
• First Posted (ESTIMATE): February 9, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): April 13, 2015
• Last Update Submitted That Met QC Criteria: April 10, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Solid tumors; Phase I; Lymphomas; 4SC-205
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma
• Other Study ID Numbers: 4SC-205-1-2009