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Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT01573780

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

A Phase 1 study testing Smac mimetic TL32711, gemcitabine hydrochloride and laboratory biomarker analysis in people with Unspecified Adult Solid Tumor, Protocol Specific, run by Roswell Park Cancer Institute at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Smac mimetic TL32711, gemcitabine hydrochloride and laboratory biomarker analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
2 sitesUnited States
Study dates
Apr 2012to Sep 2013
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 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)
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  • 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)

Who cannot join

  • 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
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  • 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
  • Myocardial infarction within the last 12 months prior to dosing with TL32711
  • QT interval corrected for heart rate (QTc) > 480 msec (including patients on medication); patients with a ventricular pacemaker for whom QT interval is not measurable may be eligible for enrollment after consultation with the Sponsor and the documentation of approval
  • Ongoing auto-immune disease or with history of an auto-immune disease within the past 5 years; a patient with a history of auto-immune disease that is currently in remission must not be receiving medication designed to control the disease and must not have experienced an exacerbation of the disease requiring treatment with immunomodulatory agents in the last 5 years; auto-immune disease includes but are not limited to systemic lupus erythematosis, scleroderma, rheumatoid arthritis, psoriasis, psoriatic arthritis, ulcerative colitis and regional enteritis (Crohn's disease)
  • Systemic or chronic topical corticosteroids or immunosuppressive therapy within 4 weeks prior to study entry or anticipated need of systemic corticosteroids or immunosuppressive therapy during study participation
  • Patients with a healing or open wound
  • Skin lesions of Grade >= 2 severity (NCI CTCAE v4), except alopecia
  • Lack of recovery or prior adverse events to Grade =< 1 severity (NCI CTCAE v4) (except alopecia) due to medications administered prior to the first dose of TL32711
  • Patients with prior history of Bell's Palsy
  • Any other condition or finding that in the opinion of the investigator may render the patient at excessive risk for treatment complications or may not be able to provide evaluable outcome information
  • Pregnant or breast-feeding women
  • Known allergy to any of the formulation components of TL32711 including citric acid monohydrate, sodium citrate dehydrate, and sodium chloride

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

Official title: A Phase I Study of TL32711 In Combination With Gemcitabine in Patients With Advanced Solid Tumors

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

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) and recommended Phase II dose of TL32711 (smac mimetic TL32711) in combination with gemcitabine (gemcitabine hydrochloride) in patients with advanced solid tumors.

SECONDARY OBJECTIVES:

  1. To determine the toxicity and safety profile of TL32711 in combination with gemcitabine in patients with advanced solid tumors.

II. To determine the pharmacokinetic profile of TL32711 and gemcitabine when administered in combination.

III. To determine the preliminary efficacy of the study combination in patients with advanced solid tumors.

IV. To determine the relationship between predictive biomarkers and clinical activity using archival tumor tissue samples for biomarker analysis.

OUTLINE: This is a dose-escalation study of smac mimetic TL32711.

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

After completion of study treatment, patients are followed up for at least 4 weeks.

Being tested
Smac mimetic TL32711, gemcitabine hydrochloride, laboratory biomarker analysis, pharmacological study, biopsy

What participants receive

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

  • Smac mimetic TL32711Drug

    Also called TL32711

    Given IV

  • gemcitabine hydrochlorideDrug

    Also called dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • biopsyProcedure or surgery

    Also called biopsies

    Optional correlative studies

Study groups in NCT01573780
Study groupRoleWhat they receive
Treatment (enzyme inhibitor therapy)ExperimentalPatients 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.
Receives: Drug: Smac mimetic TL32711; Drug: gemcitabine hydrochloride; Other: laboratory biomarker analysis; Other: pharmacological study; Procedure: biopsy

What is being measured

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

  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.

    Measured: During the first course (21 days)

Secondary outcomes (4)

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

    Summarized with frequencies and descriptive measures, and tabulated according to body system, severity and relation to treatment.

    Measured: Up to 4 weeks post-treatment

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

    Data presented in tabular format and summarized descriptively.

    Measured: Up to 4 weeks post-treatment

  3. Progression-free survival

    Measured: Up to 2 years

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

    Comparison of pharmacokinetic parameters among the dose levels and drug-drug interaction performed using non-parametric statistical methods for K-independent samples.

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

Timeline

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

  1. First posted10 Apr 2012 (estimated)
  2. Study startApr 2012
  3. Primary completionSep 2013

Why it stopped: Sponsor did not have funds to continue study

Resources

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
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01573780
Sponsor's protocol ID
I 210811
Other IDs
NCI-2012-00202
Status last verified
Aug 2022
First submitted
13 Mar 2012
Last updated
15 Aug 2022
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Smac mimetic TL32711, gemcitabine hydrochloride and laboratory biomarker analysis in people with Unspecified Adult Solid Tumor, Protocol Specific, run by Roswell Park Cancer Institute at 2 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 15 inclusion and 26 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: stopped early, as of the sponsor's last update on 15 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 was stopped early (reason given: Sponsor did not have funds to continue study). Results are not available in the source record.

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?

MTD of smac mimetic TL32711 (time frame: During the first course (21 days)). 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 NCT01573780.

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 15 Aug 2022.

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