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

NCT01078649 | Completed Phase 1

• 1 other identifier: Debio 1143-101 (AT-406-CS-001)
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 3

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).

Conditions

Cancer; Solid Tumors; Lymphoma; Malignancy

Keywords

cancer; solid tumors; lymphoma; smac mimetic; IAP inhibitor; Phase I; Dose escalation

Outcome Measures

Primary Outcomes (1)

• Maximally Tolerated Dose

  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 Outcomes (4)

• Pharmacokinetic

  Days 1-5 of Cycle 1

• Pharmacodynamic

  Cycle 1

• Efficacy

  After a minimum of 2 cycles.

• Correlation of Efficacy to Pharmacokinetic and/or Pharmacodynamic Effects of Debio 1143 (AT-406)

  Anytime during Debio 1143 (AT-406) treatment

Study Arms (1)

Debio 1143 (AT-406)

EXPERIMENTAL

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

Drug: Debio 1143 (AT-406)

Interventions

Debio 1143 (AT-406) 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.

Debio 1143 (AT-406)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Debiopharm International SA: lead

Study Sites (3)

University of Michigan Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• 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.

  PMID: 25716544 DERIVED

MeSH Terms

Conditions

Neoplasms; Lymphoma

Interventions

N-benzhydryl-5-(2-(methylamino)propanamido)-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo(1,2-a)(1,5)diazocine-8-carboxamide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Claudio Zanna, MD

  Debiopharm SA

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2010
• First Posted: March 2, 2010
• Study Start: March 29, 2010
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: December 27, 2018

Record last verified: 2018-12

Locations

US (3)