CancerPhase 1NCT01078649

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

A Phase 1 study testing Debio 1143 (AT-406) in people with Cancer and Solid Tumors, run by Debiopharm International SA at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Cancer, Solid Tumors, Lymphoma
What is being tested?: Debio 1143 (AT-406)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 51 participants
Where: 3 sitesUnited States
Study dates: 29 Mar 2010to Apr 2014
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

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

Other trials in United States

About this study

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

Read the 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
Being tested: Debio 1143 (AT-406)
Keywords: cancer, solid tumors, lymphoma, smac mimetic, IAP inhibitor, Phase I, Dose escalation
Medical subject headings: Neoplasms, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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.

Study groups in NCT01078649
Study group	Role	What they receive
Debio 1143 (AT-406)	Experimental	Open label study. All patients participating in the study will receive Debio 1143 (AT-406). Receives: Drug: Debio 1143 (AT-406)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 1 cycle, or any time during treatment

Secondary outcomes (4)

Pharmacokinetic
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).
Measured: Days 1-5 of Cycle 1
Pharmacodynamic
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.
Measured: Cycle 1
Efficacy
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.
Measured: After a minimum of 2 cycles.
Correlation of Efficacy to Pharmacokinetic and/or Pharmacodynamic Effects of Debio 1143 (AT-406)
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).
Measured: Anytime during Debio 1143 (AT-406) treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

29 Mar 2010Apr 2014

First posted2 Mar 2010 (estimated)
Study start29 Mar 2010
Primary completionApr 2014
Study completionApr 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 51 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01078649
Sponsor's protocol ID: Debio 1143-101 (AT-406-CS-001)
Status last verified: Dec 2018
First submitted: 1 Mar 2010
Last updated: 27 Dec 2018
Results posted: No
Data monitoring committee: No

Publications

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.
PubMed 25716544

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 27 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01078649
Acronym / sponsor ID: Debio 1143-101 (AT-406-CS-001)
Conditions: Cancer, Solid Tumors, Lymphoma, Malignancy
Keywords: cancer, solid tumors, lymphoma, smac mimetic, IAP inhibitor, Phase I, Dose escalation
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 51 participants (actual)
Lead sponsor: Debiopharm International SAIndustry (pharma, biotech, devices)
Study start: 29 Mar 2010 (actual)
Primary completion: Apr 2014 (actual)
Study completion: Apr 2014 (actual)
First posted: 2 Mar 2010 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Debio 1143 (AT-406)	Experimental	Drug: Debio 1143 (AT-406)Open label study. All patients participating in the study will receive Debio 1143 (AT-406).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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

Key exclusion criteria (8 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
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.	Drug	Debio 1143 (AT-406)

Primary outcome

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.

4 secondary outcomes

Pharmacokinetic
Time frame: Days 1-5 of Cycle 1
Pharmacodynamic
Time frame: Cycle 1
Efficacy
Time frame: 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

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2018.
Derived from this study: PubMed 25716544Hurwitz 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Claudio Zanna, MD study director

Debiopharm SA

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Debio 1143 (AT-406) in people with Cancer and Solid Tumors, run by Debiopharm International SA at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximally Tolerated Dose (time frame: 1 cycle, or any time during treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01078649, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2018.