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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


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Cancer, Solid Tumors, Lymphoma, Malignancy

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Trial Information

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


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.


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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximally Tolerated Dose

Outcome Description:

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.

Outcome Time Frame:

1 cycle, or any time during treatment

Safety Issue:

Yes

Principal Investigator

Claudio Zanna, MD

Investigator Role:

Study Director

Investigator Affiliation:

Debiopharm SA

Authority:

United States: Food and Drug Administration

Study ID:

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

NCT ID:

NCT01078649

Start Date:

February 2010

Completion Date:

August 2013

Related Keywords:

  • Cancer
  • Solid Tumors
  • Lymphoma
  • Malignancy
  • cancer
  • solid tumors
  • lymphoma
  • smac mimetic
  • IAP inhibitor
  • Phase I
  • Dose escalation
  • Neoplasms
  • Lymphoma

Name

Location

Mayo ClinicRochester, Minnesota  55905
Duke University Medical CenterDurham, North Carolina  27710
University of Michigan Cancer CenterAnn Arbor, Michigan  48109