CancerPhase 1/2NCT01188499
Dose Escalation, Combination Chemotherapy Safety Study of Birinapant (TL32711), in Subjects With Advanced or Metastatic Solid Tumors
A Phase 1/2 study testing Birinapant in people with Cancer, run by TetraLogic Pharmaceuticals at 7 sites in United States.
Trial summary
This is a dose escalation safety study of birinapant (TL32711) in combination with chemotherapy in subjects with advanced or metastatic solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- Birinapant
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 176 participants
- Where
- 7 sitesUnited States
- Study dates
- Oct 2010to Mar 2014
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Confirmed advanced or metastatic malignancy for which the proposed chemotherapy regimen is appropriate in the judgment of the Investigator.
- Prior therapy in dose-escalation and expansion cohorts:
- Dose-escalation cohorts: Subjects may be naïve or may have received prior therapy with the specific chemotherapeutic agent(s) being recommended in the combination arm, provided the subject did not experience life-threatening toxicity attributed to the specific agent(s).
- Expansion cohorts: Subjects have advanced colorectal cancer that had been previously determined to be KRAS mutant. Subjects naïve to irinotecan may be enrolled, and the KRAS mutation status may be wild type or mutant. Subjects previously treated with an irinotecan containing regimen may be enrolled only if they have been previously determined to be KRAS wild type. The irinotecan regimen must not have been associated with life threatening adverse events.
- Subjects evaluated for Arm 5 (liposomal doxorubicin) may not have received >300 mg/m2 cumulative dose of anthracycline.
- Life expectancy >3 months.
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- Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
- Adequate renal function
- Adequate hepatic function
- Adequate bone marrow function
- Women of childbearing potential must have a negative serum pregnancy test.
- Women of childbearing potential must agree to use 2 methods of adequate contraception (ie, hormonal and barrier method) prior to enrollment, during the study, and for a period of 30 days following the last dose of TL32711. Males who are sexually active must agree to use a condom during the study and for a period of 30 days following the last dose of TL32711, and if their partner is of childbearing potential, she must agree to use a secondary method of contraception (ie, hormonal, intrauterine device, barrier) during the study and for a period of 30 days following the last dose of TL32711.
Who cannot join
- Recent anti-cancer treatment defined as:
- Standard or investigational anti-cancer therapy within 4 weeks prior to first dose of TL32711. Exception: continued hormonal interventions for prostate cancer.
- Radiation therapy within 2 weeks prior to the first dose of TL32711.
- Major surgery within 4 weeks prior to the first dose of TL32711. Subjects must be well recovered from acute effects of surgery prior to enrollment.
- Known or suspected diagnosis of human immunodeficiency virus or chronic active Hepatitis B or C.
- Symptomatic or uncontrolled brain metastases requiring current treatment.
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- Impaired cardiac function or clinically significant cardiac disease
- QT interval corrected for heart rate (QTcB) >480 msec (including subjects on medication).
- Lack of recovery of prior adverse events to Grade ≤1 severity (NCI CTCAE v4) (except alopecia) due to therapy administered prior to the initiation of study drug dosing.
- Nursing or pregnant women.
- Known allergy to any of the formulation components of TL32711.
- Any concurrent disease and/or medical condition that in the opinion of the Investigator that would prevent the subject's participation, render the subject at excessive risk (including excessive risks due to the toxicity profile of the planned combination chemotherapeutic regimen), or limit the subject's compliance with the protocol's required evaluations.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Roswell Park Cancer Institute
Buffalo, New York, 14263
Mary Crowley Cancer Research Center
Dallas, Texas, 75201
Barbara Ann Karmanos Cancer Center
Detroit, Michigan, 48201
Holy Cross Hospital
Fort Lauderdale, Florida, 33308
University of Pennsylvania Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
South Texas Accelerated Research Therapeutics (START)
San Antonio, Texas, 78229
About this study
Official title: A Phase 1B/2A, Open-label, Non-randomized, Multi-arm Study of TL32711 in Combination With Chemotherapy in Subjects With Advanced or Metastatic Solid Tumors
This is a dose escalation safety study of birinapant (TL32711) in combination with chemotherapy in subjects with advanced or metastatic solid tumors.
Read the detailed description
The purpose of this study is to determine the safety and maximum tolerated dose of birinapant (TL32711) as a 30 minute intravenous infusion once a week, for 2 consecutive weeks, when combined with standard regimens of chemotherapy in subjects with advanced or metastatic solid tumors. Additionally the study will assess anti-tumor activity, pharmacokinetics, and exploratory biomarkers as a measurement of pharmacodynamic effects.
- Conditions
- Cancer
- Being tested
- Birinapant
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BirinapantDrug
Also called TL32711
| Study group | Role | What they receive |
|---|---|---|
| Carboplatin/Paclitaxel + Birinapant | Experimental | Carboplatin (AUC 6/Paclitaxel (175 mg/m2/IV) once every 3 (q3) weeks + birinapant (TL32711) once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). Receives: Drug: Birinapant |
| Irinotecan + Birinapant | Experimental | Irinotecan (350 mg/m2/IV) once every 3 (q3) weeks + birinapant (TL32711) once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). Receives: Drug: Birinapant |
| Docetaxel + Birinapant | Experimental | Docetaxel (75 mg/m2/IV) once every 3 (q3) weeks + birinapant (TL32711) once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). Receives: Drug: Birinapant |
| Gemcitabine + Birinapant | Experimental | Gemcitabine (1000 mg/m2/IV) once weekly (7 days +/- 2 days) for 3 consecutive weeks followed by 1 week off + birinapant (TL32711) once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 week off for each cycle (4 weeks per cycle). Receives: Drug: Birinapant |
| Liposomal Doxorubicin + Birinapant | Experimental | Liposomal doxorubicin (40 mg/m2/IV) every 4 weeks + birinapant (TL32711) once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 weeks off for each cycle (4 weeks per cycle). Receives: Drug: Birinapant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Adverse Events as a Measure of Safety and Tolerability
Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters
Measured: 1 Cycle (3-4 weeks)
Secondary outcomes (2)
Evaluation of Anti-tumor Efficacy
Tumor burden according to Response Evaluation Criteria in Solid Tumors (RECIST) and time to progression
Measured: Every 2 cycles
Evaluation of Pharmacokinetics and Translational Biomarkers
Measurement of TL32711 pharmacokinetics: Maximum plasma concentration (Cmax), area under the curve (AUC), half-life (t1/2) and assessment of translational biomarkers in plasma, PBMC's and tumor biopsies. Gene expression profiling of tumor tissue.
Measured: Cycle 1 and Cycle 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2010 (estimated)
- Study startOct 2010
- Primary completionOct 2013
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 176 participants (actual)
Sponsor and investigators
- Lead sponsor
- TetraLogic Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- John N Nemunaitis, MD, Principal investigator, Mary Crowley Cancer Research CenterRavi Amaravadi, MD, Principal investigator, University of Pennsylvania, Abramson Cancer CenterLainie P Martin, MD, Principal investigator, Fox Chase Cancer CenterAlex Adjei, MD, PhD, Principal investigator, Roswell Park Cancer InstitutePatricia LoRusso, DO, Principal investigator, Barbara Ann Karmanos Cancer CenterKyriakos P Papadopoulos, MD, Principal investigator, South Texas Accelerated Research Therapeutics (START)Zdenka Segota, MD, Principal investigator, Holy Cross Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01188499
- Sponsor's protocol ID
- TL32711-POC-0078-PTL
- Status last verified
- Apr 2016
- First submitted
- 23 Aug 2010
- Last updated
- 30 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1B/2A, Open-label, Non-randomized, Multi-arm Study of TL32711 in Combination With Chemotherapy in Subjects With Advanced or Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT01188499
- Acronym / sponsor ID
- TL32711-POC-0078-PTL
- Conditions
- Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 176 participants (actual)
- Lead sponsor
- TetraLogic PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Oct 2010
- Primary completion
- Oct 2013 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 25 Aug 2010 (estimated)
- Results
- Posted 30 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a dose escalation safety study of birinapant (TL32711) in combination with chemotherapy in subjects with advanced or metastatic solid tumors.
Detailed description
The purpose of this study is to determine the safety and maximum tolerated dose of birinapant (TL32711) as a 30 minute intravenous infusion once a week, for 2 consecutive weeks, when combined with standard regimens of chemotherapy in subjects with advanced or metastatic solid tumors. Additionally the study will assess anti-tumor activity, pharmacokinetics, and exploratory biomarkers as a measurement of pharmacodynamic effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Carboplatin/Paclitaxel + Birinapant | Experimental | Drug: BirinapantCarboplatin (AUC 6/Paclitaxel (175 mg/m2/IV) once every 3 (q3) weeks + birinapant (TL32711) once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). |
| Irinotecan + Birinapant | Experimental | Drug: BirinapantIrinotecan (350 mg/m2/IV) once every 3 (q3) weeks + birinapant (TL32711) once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). |
| Docetaxel + Birinapant | Experimental | Drug: BirinapantDocetaxel (75 mg/m2/IV) once every 3 (q3) weeks + birinapant (TL32711) once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). |
| Gemcitabine + Birinapant | Experimental | Drug: BirinapantGemcitabine (1000 mg/m2/IV) once weekly (7 days +/- 2 days) for 3 consecutive weeks followed by 1 week off + birinapant (TL32711) once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 week off for each cycle (4 weeks per cycle). |
| Liposomal Doxorubicin + Birinapant | Experimental | Drug: BirinapantLiposomal doxorubicin (40 mg/m2/IV) every 4 weeks + birinapant (TL32711) once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 weeks off for each cycle (4 weeks per cycle). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Confirmed advanced or metastatic malignancy for which the proposed chemotherapy regimen is appropriate in the judgment of the Investigator.
- Prior therapy in dose-escalation and expansion cohorts:
- Subjects evaluated for Arm 5 (liposomal doxorubicin) may not have received >300 mg/m2 cumulative dose of anthracycline.
- Life expectancy >3 months.
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
Key exclusion criteria (12 listed)
- Recent anti-cancer treatment defined as:
- Known or suspected diagnosis of human immunodeficiency virus or chronic active Hepatitis B or C.
- Symptomatic or uncontrolled brain metastases requiring current treatment.
- Impaired cardiac function or clinically significant cardiac disease
- QT interval corrected for heart rate (QTcB) >480 msec (including subjects on medication).
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 |
|---|---|---|
| BirinapantAlso: TL32711 | Drug | Carboplatin/Paclitaxel + Birinapant, Docetaxel + Birinapant, Gemcitabine + Birinapant, Irinotecan + Birinapant, Liposomal Doxorubicin + Birinapant |
Primary outcome
Number of Subjects With Adverse Events as a Measure of Safety and Tolerability
Time frame: 1 Cycle (3-4 weeks)
Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters
2 secondary outcomes
Evaluation of Anti-tumor Efficacy
Time frame: Every 2 cycles
Evaluation of Pharmacokinetics and Translational Biomarkers
Time frame: Cycle 1 and Cycle 2
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
John N Nemunaitis, MD principal investigator
Mary Crowley Cancer Research Center
Ravi Amaravadi, MD principal investigator
University of Pennsylvania, Abramson Cancer Center
Lainie P Martin, MD principal investigator
Fox Chase Cancer Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Birinapant in people with Cancer, run by TetraLogic Pharmaceuticals at 7 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 12 inclusion and 12 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 30 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Subjects With Adverse Events as a Measure of Safety and Tolerability (time frame: 1 Cycle (3-4 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 May 2016.