A Phase 1 Study Evaluating AMG 232 in Advanced Solid Tumors or Multiple Myeloma

Cancer Clinical Trial

Official title:

A Phase 1 First-in-Human Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 232 in Adult Subjects With Advanced Solid Tumors or Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01723020
• Other study ID #: 20120106
• Status: Completed
• Phase: Phase 1
• Start date: December 27, 2012
• Est. completion date: September 25, 2017

Study information

• Verified date: August 2021
• Source: Kartos Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

First in human, open-label, sequential dose escalation and expansion study of AMG 232 in subjects with advanced solid tumors or multiple myeloma

Description:

Study Design: This is an open-label, dose exploration study evaluating AMG 232 in subjects with advanced p53WT solid tumors or multiple myeloma. The study will be conducted in 2 parts: Part 1 - Dose Exploration (parts 1a, 1b and 1c) and Part 2 - Dose Expansion. Part 1a is aimed at evaluating the safety, tolerability, PK and PD of AMG 232 and determining the MTD of a 7-day once daily (QD) dosing schedule in subjects with advanced solid tumors using a practical continuous reassessment method (CRM). Part 1b will evaluate the safety and tolerability of 3-day QD dosing schedule (or alternate dosing schedule based upon emerging data) with a particular emphasis on evaluating the tolerability of daily doses equal to or higher than the part 1a MTD in subjects with solid tumors or multiple myeloma. Part 1c will evaluate the safety and tolerability of 7-day twice daily (BID) dosing schedule with daily cumulative doses equal to or higher than the part 1a MTD in subjects with solid tumors. The dose expansion part of the study (Part 2) can open once the MTD has been determined in Part 1a. Part 2, part 1b and part 1c can be explored in parallel. The dose expansion part will consist of up to 85 additional subjects with specific tumors harboring MDM2 amplification (liposarcoma [LPS], gliobastoma [ GBM ] and all other solid tumors) or potentially harboring MDM2 overexpression (ER+ metastatic breast cancer) and a group of subjects with multiple myeloma.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 107
• Est. completion date: September 25, 2017
• Est. primary completion date: March 15, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Men or women > 18 years old

• Pathologically documented, definitively diagnosed, advanced solid tumor that is refractory to standard treatment, or which no standard therapy is available, or the subject refuses standard therapy or multiple myeloma

• Willing to undergo pre-dose core needle tumor biopsies or bone marrow aspirate for subjects with multiple myeloma.

• Ability to take oral medications and willing to record daily adherance to investigational product

• Adequate hematological, renal, hepatic, and coagulation laboratory assessments

Exclusion Criteria:

• Active brain metastases

• For solid tumor-History or presence of hematological malignancies unless curatively treated with no evidence of disease for greater than or equal to 5 years

• Active infection requiring intravenous (IV) antibiotics

• Anti-tumor therapy

• Therapeutic or palliative radiation therapy within 30 days of starting treatment

• Currently enrolled in another investigational device or drug study

Related Conditions & MeSH terms

• Advanced Malignancy
• Advanced Solid Tumors
• Cancer
• Glioblastoma
• Multiple Myeloma
• Neoplasms
• Neoplasms, Plasma Cell
• Oncology
• Oncology Patients
• Tumors

Intervention

Drug:
• AMG 232
Given an an oral tablet in escalating doses.

Locations

Country	Name	City	State
France	Research Site	Lyon CEDEX 08
France	Research Site	Villejuif
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Rotterdam
Netherlands	Research Site	Utrecht
United States	Research Site	Boston	Massachusetts
United States	Research Site	Boston	Massachusetts
United States	Greenville Hospital System	Greenville	South Carolina
United States	Research Site	Greenville	South Carolina
United States	Research Site	Hackensack	New Jersey
United States	Research Site	New Brunswick	New Jersey
United States	Research Site	New York	New York
United States	Research Site	Norwalk	Connecticut
United States	Research Site	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Kartos Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  France,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of AMG 232	Subject incidence of adverse events, dose limiting toxicities, and clinically significant changes in vital signs, weight, ECGs and clinical laboratory tests	36 months
Secondary	Objective Tumor Response	Duration of overall response and duration of stable disease measured by CT or MRI and assessed per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, for multiple myeloma using IMWG response criteria	36 months

External Links

•   AmgenTrials clinical trials website