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

Sponsor

Kartos Therapeutics, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01723020

Collaborator

(none)

107

Enrollment

Locations

Arm

56.9

Actual Duration (Months)

7.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Advanced Malignancy Advanced Solid Tumors Cancer Oncology Oncology Patients Tumors Glioblastoma Multiple Myeloma	Drug: AMG 232	Phase 1

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

107 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 27, 2012

Actual Primary Completion Date :

Mar 15, 2017

Actual Study Completion Date :

Sep 25, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AMG 232 AMG 232 is an anti-cancer agent.	Drug: AMG 232 Given an an oral tablet in escalating doses.

Arm

Intervention/Treatment

Experimental: AMG 232

AMG 232 is an anti-cancer agent.

Drug: AMG 232

Given an an oral tablet in escalating doses.

Outcome Measures

Primary Outcome Measures

Safety of AMG 232 [36 months]
Subject incidence of adverse events, dose limiting toxicities, and clinically significant changes in vital signs, weight, ECGs and clinical laboratory tests

Secondary Outcome Measures

Objective Tumor Response [36 months]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Santa Monica	California	United States	90403
2	Research Site	Norwalk	Connecticut	United States	06856
3	Research Site	Boston	Massachusetts	United States	02115
4	Research Site	Boston	Massachusetts	United States	02215
5	Research Site	Hackensack	New Jersey	United States	07601
6	Research Site	New Brunswick	New Jersey	United States	08901
7	Research Site	New York	New York	United States	10021
8	Greenville Hospital System	Greenville	South Carolina	United States	29605
9	Research Site	Greenville	South Carolina	United States	29605
10	Research Site	Lyon CEDEX 08		France	69373
11	Research Site	Villejuif		France	94805
12	Research Site	Amsterdam		Netherlands	1066 CX
13	Research Site	Rotterdam		Netherlands	3015 CE
14	Research Site	Utrecht		Netherlands	3584 CX