Gemcitabine Hydrochloride and Smac Mimetic TL32711 in Treating Patients With Advanced Solid Tumors

NCT01573780 | Terminated Phase 1

• 2 other identifiers: I 210811NCI-2012-00202
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine the dose of smac mimetic TL32711 that is safe and tolerated when given with gemcitabine hydrochloride to patients with advanced cancer

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (1)

• MTD of smac mimetic TL32711

  Defined as the highest dose level at which less than 2 of 6 patients experience study treatment-related dose-limiting toxicity. Summarized with frequencies and descriptive measures, and tabulated according to body system, severity and relation to treatment.

  During the first course (21 days)

Secondary Outcomes (4)

• Overall toxicity profile characterized by type, frequency, severity (according to the NCI CTCAE version 4.0), timing, seriousness, and relationship to study treatment

  Up to 4 weeks post-treatment

• Response rates according to the RECIST v1.1 (solid tumor/dose-finding cohort)

  Up to 4 weeks post-treatment

• Progression-free survival

  Up to 2 years

• Plasma pharmacokinetic parameters of smac mimetic TL32711, gemcitabine hydrochloride and its metabolites

  Days 1 and 8 of course 1 and then day 1 of course 2 (day 22)

Study Arms (1)

Treatment (enzyme inhibitor therapy)

EXPERIMENTAL

Patients receive gemcitabine hydrochloride IV over 30 minutes and smac mimetic TL32711 IV over 30 minutes once weekly for 2 weeks. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Smac mimetic TL32711; Drug: gemcitabine hydrochloride; Other: laboratory biomarker analysis; Other: pharmacological study; Procedure: biopsy

Interventions

Smac mimetic TL32711 DRUG

Given IV

Also known as: TL32711

Treatment (enzyme inhibitor therapy)

gemcitabine hydrochloride DRUG

Given IV

Also known as: dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar

Treatment (enzyme inhibitor therapy)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (enzyme inhibitor therapy)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (enzyme inhibitor therapy)

biopsy PROCEDURE

Optional correlative studies

Also known as: biopsies

Treatment (enzyme inhibitor therapy)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed solid tumors that are advanced or metastatic that gemcitabine-based treatment is considered standard therapy
• Patient must consent to the use of their archival tumor tissue for protocol use if available
• Patient with at least one measurable site of disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 that has not been previously irradiated
• Eastern Cooperative Oncology Group (ECOG) Performance Status =\< 1
• Life expectancy \>= 3 months
• Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3 (system international \[SI\] units 1.5 x 10\^6/L)
• Platelets \>= 100,000 cells/m\^3 (SI units 100 x 10\^6/L)
• Hemoglobin \>= 9.0 g/dL (SI units 90 g/L) (in the absence of transfusion within 24 hours prior to dosing)
• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGPT) and alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =\< 3 x Upper Limit of Normal (ULN); In patients with known hepatic involvement, AST and ALT \< 5 x ULN are allowed
• Total bilirubin =\< 1.5 x ULN; in patients with known hepatic involvement, total bilirubin =\< 1.5 x ULN is allowed
• Serum creatinine =\< 1.5 x ULN, or 24-hr urine creatinine clearance calculation \>= 60 mL/min
• Willing and able to comply with scheduled visits, treatment plan and laboratory tests
• Ability to understand and willingness to sign a written informed consent; a signed informed consent must be obtained prior to any study specific procedures
• Women of childbearing potential must have a negative serum pregnancy test at screening and negative (serum or urine) pregnancy test within 48 hours prior to the first dose of the first cycle of study treatment
• Women of childbearing potential must agree to use 2 methods of adequate contraception (i.e., hormonal and barrier method) prior to enrollment, during the study, and for a period of 30 days following the last dose of study drug(s); males who are sexually active must agree to use a condom during the study for a period of 30 days following the last dose of study drug(s), and if their partner is of childbearing potential, she must agree to use a secondary method of contraception (i.e., hormonal, intrauterine device, barrier) during the study and for a period of 30 days following the last dose of study drug(s)

You may not qualify if:

• Patients who have receive recent anti-cancer therapy defined by:
• Chemotherapy, immunotherapy, hormonal therapy and monoclonal antibodies (but excluding nitrosourea, mitomycin-C, targeted therapy and radiation) =\< 4 weeks prior to starting study drug, or who have not recovered from side effects of such therapy
• Last administration of nitrosourea or mitomycin-C =\< 6 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy; or
• Targeted therapy (e.g. sunitinib, sorafenib, pazopanib) =\< 2 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy; or
• Radiotherapy =\< 4 weeks prior to starting study drug, or =\< 2 weeks prior to starting study drug in the case of localized radiotherapy (e.g. for analgesic purpose or for lytic lesions at risk of fracture), or who have not recovered from radiotherapy toxicities
• Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury =\< 4 weeks prior to starting study treatment, or patients who have had minor procedures, percutaneous biopsies or placement of vascular access device =\< 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury
• Uncontrolled concurrent illness, including but not limited to ongoing or active serious infection requiring systemic antimicrobials (within 2 weeks prior to first dose of TL32711), arterial hypertension (\> 160/100 mm/Hg on antihypertensive medications), uncontrolled endocrine diseases, altered mental status or psychiatric illness/social situations that would limit compliance with protocol requirements and/or obscure study results
• Known or suspected diagnosis of human immunodeficiency virus (HIV) or chronic active Hepatitis B or C; viral testing is not required
• Inability to start prophylactic anti-viral medication
• Clinically significant pulmonary illness resulting in Grade \>= 2 hypoxia (National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE, v4\]) or any requirement for supplemental oxygen, or pulse oximetry less than 90% saturation on room air
• Symptomatic or uncontrolled brain metastases requiring current treatment (less than 4 weeks from last cranial radiation or 4 weeks from last steroids)
• Impaired cardiac function or clinically significant cardiac disease including the following:
• Clinically significant arrhythmias (except chronic well controlled atrial fibrillation)
• New York Heart Association (NYHA) grade II, III, or IV congestive heart failure
• Angina pectoris =\< 6 months prior to dosing with TL32711

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• TetraLogic Pharmaceuticals: collaborator

Study Sites (2)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

MeSH Terms

Interventions

birinapant; Gemcitabine; Biopsy

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Wen Wee Ma

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 13, 2012
• First Posted: April 10, 2012
• Study Start: April 1, 2012
• Primary Completion: September 1, 2013
• Last Updated: August 15, 2022

Record last verified: 2022-08

Locations

US (2)