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

NCT ID: NCT01078649

Last Updated: 2018-12-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-29
• Study Completion Date: 2014-04-30

Brief Summary

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).

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.

Conditions

Cancer; Solid Tumors; Lymphoma; Malignancy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Debio 1143 (AT-406)

Open label study. All patients participating in the study will receive Debio 1143 (AT-406).

Group Type: EXPERIMENTAL

Debio 1143 (AT-406)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Debiopharm International SA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Claudio Zanna, MD

Role: STUDY_DIRECTOR

Debiopharm SA

Locations

University of Michigan Cancer Center

Ann Arbor, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

References

Hurwitz HI, Smith DC, Pitot HC, Brill JM, Chugh R, Rouits E, Rubin J, Strickler J, Vuagniaux G, Sorensen JM, Zanna C. Safety, pharmacokinetics, and pharmacodynamic properties of oral DEBIO1143 (AT-406) in patients with advanced cancer: results of a first-in-man study. Cancer Chemother Pharmacol. 2015 Apr;75(4):851-9. doi: 10.1007/s00280-015-2709-8. Epub 2015 Feb 27.

Reference Type: DERIVED

PMID: 25716544 (View on PubMed)

Other Identifiers

Debio 1143-101 (AT-406-CS-001)

Identifier Type: -

Identifier Source: org_study_id