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Dose Escalation, Combination Chemotherapy Safety Study of TL32711, in Subjects With Advanced or Metastatic Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
TetraLogic Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01188499
First received: August 23, 2010
Last updated: May 7, 2014
Last verified: May 2014
  Purpose

This is a dose escalation safety study of TL32711 in combination with chemotherapy in subjects with advanced or metastatic solid tumors.


Condition Intervention Phase
Cancer
Drug: TL32711
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by TetraLogic Pharmaceuticals:

Primary Outcome Measures:
  • Number of subjects with adverse events as a measure of safety and tolerability [ Time Frame: 1 Cycle (3-4 weeks) ] [ Designated as safety issue: Yes ]
    Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters


Secondary Outcome Measures:
  • Evaluation of anti-tumor efficacy [ Time Frame: Every 2 cycles ] [ Designated as safety issue: No ]
    Tumor burden according to Response Evaluation Criteria in Solid Tumors (RECIST) and time to progression

  • Evaluation of pharmacokinetics and translational biomarkers [ Time Frame: Cycle 1 and Cycle 2 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 200
Study Start Date: October 2010
Study Completion Date: May 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Carboplatin/Paclitaxel + TL32711
Carboplatin (AUC 6/Paclitaxel (175 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).
Drug: TL32711
30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
Other Names:
  • Paraplatin
  • Taxol
  • Camptosar
  • Taxotere
Experimental: Irinotecan + TL32711
Irinotecan (350 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).
Drug: TL32711
30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
Other Names:
  • Paraplatin
  • Taxol
  • Camptosar
  • Taxotere
Experimental: Docetaxel + TL32711
Docetaxel (75 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).
Drug: TL32711
30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
Other Names:
  • Paraplatin
  • Taxol
  • Camptosar
  • Taxotere
Experimental: Gemcitabine + TL32711
Gemcitabine (1000 mg/m2/IV) once weekly (7 days +/- 2 days) for 3 consecutive weeks followed by 1 week off + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 week off for each cycle (4 weeks per cycle).
Drug: TL32711
30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy.
Other Names:
  • Gemzar
  • Doxil
Experimental: Liposomal doxorubicin
Liposomal doxorubicin (40 mg/m2/IV) every 4 weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 weeks off for each cycle (4 weeks per cycle).
Drug: TL32711
30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy.
Other Names:
  • Gemzar
  • Doxil

Detailed Description:

The purpose of this study is to determine the safety and maximum tolerated dose of 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 may not have received prior therapy with the specific combination chemotherapeutic agent(s) in the expansion arm. No more than 2 prior cytotoxic chemotherapy regimens for advanced or metastatic disease are allowed.
  • 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.
  • 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.

Exclusion Criteria:

  • 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.
  • Impaired cardiac function or clinically significant cardiac disease including the following:
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01188499

Locations
United States, Michigan
Barbara Ann Karmanos Cancer Center
Detroit, Michigan, United States, 48201
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
University of Pennsylvania Abramson Cancer Center
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Mary Crowley Medical Research Center
Dallas, Texas, United States, 75201
South Texas Accelerated Research Therapeutics (START)
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
TetraLogic Pharmaceuticals
Investigators
Principal Investigator: Neil N Senzer, MD Mary Crowley Medical Research Center
Principal Investigator: Ravi Amaravadi, MD University of Pennsylvania, Abramson Cancer Center
Principal Investigator: Lainie P Martin, MD Fox Chase Cancer Center
Principal Investigator: Alex Adjei, MD, PhD Roswell Park Cancer Institute
Principal Investigator: Patricia LoRusso, DO Barbara Ann Karmanos Cancer Center
Principal Investigator: Kyriakos P Papadopoulos, MD South Texas Accelerated Research Therapeutics (START)
  More Information

No publications provided

Responsible Party: TetraLogic Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01188499     History of Changes
Other Study ID Numbers: TL32711-POC-0078-PTL
Study First Received: August 23, 2010
Last Updated: May 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 20, 2014