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

Purpose

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).

Condition	Intervention	Phase
Cancer Solid Tumors Lymphoma Malignancy	Drug: Debio 1143 (AT-406)	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lymphoma

U.S. FDA Resources

Further study details as provided by Debiopharm S.A.:

Primary Outcome Measures:

Maximally Tolerated Dose [ Time Frame: 1 cycle, or any time during treatment ] [ Designated as safety issue: Yes ]
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.

Secondary Outcome Measures:

Pharmacokinetic [ Time Frame: Days 1-5 of Cycle 1 ] [ Designated as safety issue: Yes ]
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).
Pharmacodynamic [ Time Frame: Cycle 1 ] [ Designated as safety issue: No ]
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.
Efficacy [ Time Frame: After a minimum of 2 cycles. ] [ Designated as safety issue: No ]
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.
Correlation of Efficacy to Pharmacokinetic and/or Pharmacodynamic Effects of Debio 1143 (AT-406) [ Time Frame: Anytime during Debio 1143 (AT-406) treatment ] [ Designated as safety issue: No ]
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).

Estimated Enrollment:	50
Study Start Date:	February 2010
Estimated Study Completion Date:	August 2013
Estimated Primary Completion Date:	July 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01078649

Contacts

Contact: Jorge Liz

jliz@debiopharm.com

Locations

United States, Michigan
University of Michigan Cancer Center	Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Kim Feldhaus, RN, BSN 734-615-6639 kfeldha@med.umich.edu
Principal Investigator: David Smith, MD
United States, Minnesota
Mayo Clinic	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Office 507-538-7623
Principal Investigator: Henry C Pitot, MD
United States, North Carolina
Duke University Medical Center	Recruiting
Durham, North Carolina, United States, 27710
Contact: Beth Spencer, RN, BSN 919-684-6342 beth.spencer@duke.edu
Principal Investigator: Herbert I Hurwitz, MD

Sponsors and Collaborators

Debiopharm S.A.

Investigators

Study Director:

Claudio Zanna, MD

Debiopharm SA

More Information

No publications provided

Responsible Party:	Debiopharm S.A.
ClinicalTrials.gov Identifier:	NCT01078649 History of Changes
Other Study ID Numbers:	Debio 1143-101 (AT-406-CS-001)
Study First Received:	March 1, 2010
Last Updated:	April 17, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Debiopharm S.A.:

cancer
solid tumors
lymphoma
smac mimetic

IAP inhibitor
Phase I
Dose escalation

Additional relevant MeSH terms:

Neoplasms
Lymphoma
Neoplasms by Histologic Type
Lymphoproliferative Disorders

Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on June 13, 2013