Dose Escalation Study of Safety and Tolerability of AT-406 in Patients With Advanced Solid Tumors and Lymphomas

December 26, 2018 updated by: Debiopharm International SA

A Phase I, Open Label, Multi-Center, Dose Escalation Study of the Safety, Tolerability, Pharmacodynamic and Pharmacokinetic Properties of Orally Administered AT-406 in Patients With Advanced Solid Tumors and Lymphomas

The purpose of this study is to determine the safety profile and the maximum dose of Debio 1143 (AT-406) that can be given to humans. This study is also designed to measure how much Debio 1143 (AT-406) gets into the blood stream (pharmacokinetics), and how Debio 1143 (AT-406) interacts with proteins related to cancer that the drug is targeted to affect (pharmacodynamics).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Ascenta Therapeutics, Inc. is conducting a clinical trial of the compound Debio 1143 (AT-406), a small molecule second mitochondria-derived activator of caspase C (Smac) mimetic. In vivo and in vitro studies have demonstrated that Debio 1143 (AT-406) induces cell death in several tumor models by inhibiting XIAP (X linked IAP), cIAP-1 (cellular IAP-1) and cIAP-2 (cellular IAP-2), thus releasing initiator and effector caspases to promote apoptosis. This protocol is a Phase I, dose-escalation, open-label, multi-center study conducted in patients with advanced solid tumors and lymphomas to evaluate the safety, tolerability and pharmacology of Debio 1143 (AT-406) in humans when administered orally.

Study Type

Interventional

Enrollment (Actual)

51

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Cancer Center
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically confirmed solid tumor or lymphoma;
  • Locally advanced or metastatic disease for which no life prolonging therapy is available and no standard therapy is judged appropriate by the investigator;
  • Eastern Cooperative Oncology Group Performance Status ≤ 1;
  • Adequate hematologic function as indicated by, ANC ≥ 1,500/mm3, Hgb >9.0 g/dL, platelet count ≥ 100,000/mm3
  • Adequate renal and liver function as indicated by serum creatinine ≤ 1.0 x ULN or creatinine clearance of > 60 cc/min, serum albumin ≥ 3.0 gm/dL, total bilirubin < 1.0 x ULN, AST and ALT ≤ 2.5 x ULN ; Alkaline phosphatase ≤2.5 x ULN
  • Negative Hepatitis B and Hepatitis C testing;
  • QTc interval ≤450ms.

Exclusion Criteria:

  • Radiation within 14 days of study entry, thoracic radiation within 28 days of study entry. Patients who have received prior radiotherapy must have discontinued steroids for 14 days prior to study entry and be clinically stable;
  • Not recovered to ≤ Grade 1 toxicity from prior radiotherapy or chemotherapy agents;
  • Use or requirement for use of aspirin or aspirin containing products with >81 mg of aspirin per day;
  • History of gastrointestinal bleeding within 1 year;
  • History of diabetes mellitus requiring treatment with oral agents or insulin;
  • Active rheumatoid arthritis, active inflammatory bowel disease, chronic infections, or any other disease or condition associated with chronic inflammation;
  • Known or suspected Wilson's Disease, or other conditions that affect copper accumulation or regulation;
  • Prior treatment with IAP inhibitors.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Debio 1143 (AT-406)
Open label study. All patients participating in the study will receive Debio 1143 (AT-406).
Drug: Debio 1143 (AT-406)
Oral Debio 1143 (AT-406) will be administered in a dose escalation study to determine the maximally tolerated dose in humans. Patients will receive Debio 1143 (AT-406) on days 1-5, and 15-19 of a 28 day cycle, or days 1-5 of a 21 day cycle, repeated until progression or unacceptable toxicity occurs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximally Tolerated Dose
Time Frame: 1 cycle, or any time during treatment
The primary endpoint of this study is to characterize the safety, and determine the maximum tolerated dose and schedule of Debio 1143 (AT-406) when administered to patients with advanced cancer. Patients will receive Debio 1143 (AT-406) on days 1-5, and 15-19 of a 28 day cycle, days 1-5 of a 21 day cycle, or days 1-14 of a 21 day cycle. For the purpose of determining the MTD, dose limiting toxicities will be evaluated at any time. For the purpose of dose escalation, dose limiting toxicities will be evaluated through the end of 1 cycle.
1 cycle, or any time during treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetic
Time Frame: Days 1-5 of Cycle 1
A secondary endpoint of this study is to determine the pharmacokinetic parameters of Debio 1143 (AT-406) in plasma and urine, and preliminary metabolism profile of Debio 1143 (AT-406).
Days 1-5 of Cycle 1
Pharmacodynamic
Time Frame: Cycle 1
A secondary endpoint of this study, provided that adequate amounts of tissue are available, is to evaluate the interaction of Debio 1143 (AT-406) with IAP family members (e.g., xIAP, cIAP-1, cIAP-2, etc.). Patient participation in this aspect of the study is optional.
Cycle 1
Efficacy
Time Frame: After a minimum of 2 cycles.
A secondary endpoint to this study is to identify any anti-tumor activity of Debio 1143 (AT-406) that may be observed in the course of the trial. Applicable solid tumor or lymphoma response criteria will be used, accordingly.
After a minimum of 2 cycles.
Correlation of Efficacy to Pharmacokinetic and/or Pharmacodynamic Effects of Debio 1143 (AT-406)
Time Frame: Anytime during Debio 1143 (AT-406) treatment
A secondary endpoint of this study is to correlate pharmacokinetic and pharmacodynamic effects of Debio 1143 (AT-406) with any observed antitumor activity of Debio 1143 (AT-406).
Anytime during Debio 1143 (AT-406) treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Debiopharm International SA

Investigators

  • Study Director: Claudio Zanna, MD, Debiopharm SA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 29, 2010

Primary Completion (Actual)

April 1, 2014

Study Completion (Actual)

April 1, 2014

Study Registration Dates

First Submitted

March 1, 2010

First Submitted That Met QC Criteria

March 1, 2010

First Posted (Estimate)

March 2, 2010

Study Record Updates

Last Update Posted (Actual)

December 27, 2018

Last Update Submitted That Met QC Criteria

December 26, 2018

Last Verified

December 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Debio 1143-101 (AT-406-CS-001)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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