PTC299 in Treating Patients With HIV-Related Kaposi Sarcoma
NCT ID: NCT00686842
Last Updated: 2018-06-06
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
TERMINATED
PHASE1/PHASE2
17 participants
INTERVENTIONAL
2008-09-30
2010-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
PURPOSE: This phase I/II trial is studying the side effects and best dose of PTC299 and to see how well it works in treating patients with HIV-related Kaposi sarcoma.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
EMD 121974 in Treating Patients With HIV-Related Kaposi's Sarcoma
NCT00006222
A Phase II Trial of COL-3 in Patients With HIV Related Kaposi's Sarcoma
NCT00020683
Gamma Secretase Inhibitor PF-03084014 in Treating Patients With AIDS-Associated Kaposi Sarcoma
NCT02137564
Paclitaxel in Treating Patients With AIDS-Related Kaposi's Sarcoma
NCT00003008
BMS-275291 in Treating Patients With HIV-Related Kaposi's Sarcoma
NCT00024024
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Primary
* To define the safety and toxicity of anti-VEGF small molecule PTC299 in patients with HIV-related Kaposi sarcoma.
* To establish the maximum tolerated dose of this drug in these patients.
* To estimate the response rate in patients treated with this drug.
Secondary
* To describe the pharmacokinetics of this drug in these patients.
* To describe the effects of this drug on serum and plasma VEGF, VEGFR, and cytokine profiles in these patients.
* To describe the effects of this drug on HIV and KSHV viral loads in these patients.
* To describe the effects of this drug on T-lymphocyte subsets (i.e., CD4 and CD8) in these patients.
* To describe the effects of this drug on VEGF, VEGFR-2 and -3, phospho-Akt, p53, and HIF-1α expression and tumor cell proliferation, as measured by Ki-67 staining, in tumor biopsy samples obtained from these patients.
* To describe the effects of this drug on viral gene expression and cellular gene transcription, as measured by real-time quantitative PCR-based profiling, in tumor biopsy samples obtained from these patients.
OUTLINE: This is a multicenter, phase I dose-escalation study of anti-VEGF small molecule PTC299 followed by a phase II study.
Patients receive oral anti-VEGF small molecule PTC299 twice daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients who do not demonstrate an objective response of their Kaposi sarcoma (KS) lesions after 6 courses of treatment are removed from the study.
Patients undergo blood sample collection and punch biopsies periodically during study for correlative laboratory studies. Biopsy samples are assessed for VEGF, VEGFR-2, VEGFR-3, phospho-Akt, KSHV LANA, orf59, p53, and HIF-1α expression by IHC; tumor cell proliferation by Ki-67 staining; and viral gene expression at the messenger RNA level and KSHV transcription by real-time quantitative PCR-based profiling. Blood samples are assessed for pharmacokinetics and levels of secreted cytokines or other potential serum markers characteristic for KS.
After completion of study treatment, patients are followed at 30 days.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
VEGF Inhibitor PTC299
Single arm study - all subjects received PTC299
VEGF inhibitor PTC299
20 mg capsules to be taken by mouth BID. Three dose levels will be evaluated: 40 mg, 80mg, and 100mg BID. Subjects will receive PTC299 in consecutive 28-day cycles for a maximum of 12 cycles.
gene expression analysis
To describe the effects of PTC299 on viral gene expression and cellular gene transcription in KS tumor biopsies using real-time QPCR-based profiling.
polymerase chain reaction
To describe the effects of PTC299 on viral gene expression and cellular gene transcription in KS tumor biopsies using real-time QPCR-based profiling.
protein expression analysis
To describe the effects of PTC299 on viral gene expression and cellular gene transcription in KS tumor biopsies using real-time QPCR-based profiling.
immunohistochemistry staining method
To describe the effects of PTC299 on KS tumor biopsies with respect to expression of VEGF, the VEGFR-2 and -3, phospho-Akt, p53, HIF-1α and proliferation, measured by Ki-67 staining.
laboratory biomarker analysis
To describe the effects of PTC299 on KS tumor biopsies with respect to expression of VEGF, the VEGFR-2 and -3, phospho-Akt, p53, HIF-1α and proliferation, measured by Ki-67 staining.
pharmacological study
To describe the pharmacokinetics of PTC299 in patients with HIV-associated KS. To describe the effects of PTC299 on circulating VEGF, VEGFR and cytokine levels in patients with HIV-associated KS.
biopsy
To describe the effects of PTC299 on KS tumor biopsies with respect to expression of VEGF, the VEGFR-2 and -3, phospho-Akt, p53, HIF-1α and proliferation, measured by Ki-67 staining.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
VEGF inhibitor PTC299
20 mg capsules to be taken by mouth BID. Three dose levels will be evaluated: 40 mg, 80mg, and 100mg BID. Subjects will receive PTC299 in consecutive 28-day cycles for a maximum of 12 cycles.
gene expression analysis
To describe the effects of PTC299 on viral gene expression and cellular gene transcription in KS tumor biopsies using real-time QPCR-based profiling.
polymerase chain reaction
To describe the effects of PTC299 on viral gene expression and cellular gene transcription in KS tumor biopsies using real-time QPCR-based profiling.
protein expression analysis
To describe the effects of PTC299 on viral gene expression and cellular gene transcription in KS tumor biopsies using real-time QPCR-based profiling.
immunohistochemistry staining method
To describe the effects of PTC299 on KS tumor biopsies with respect to expression of VEGF, the VEGFR-2 and -3, phospho-Akt, p53, HIF-1α and proliferation, measured by Ki-67 staining.
laboratory biomarker analysis
To describe the effects of PTC299 on KS tumor biopsies with respect to expression of VEGF, the VEGFR-2 and -3, phospho-Akt, p53, HIF-1α and proliferation, measured by Ki-67 staining.
pharmacological study
To describe the pharmacokinetics of PTC299 in patients with HIV-associated KS. To describe the effects of PTC299 on circulating VEGF, VEGFR and cytokine levels in patients with HIV-associated KS.
biopsy
To describe the effects of PTC299 on KS tumor biopsies with respect to expression of VEGF, the VEGFR-2 and -3, phospho-Akt, p53, HIF-1α and proliferation, measured by Ki-67 staining.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
PATIENT CHARACTERISTICS:
* Karnofsky performance status 60-100%
* Life expectancy ≥ 3 months
* Absolute neutrophil count ≥ 1,000/mm³
* Platelet count ≥ 75,000/mm³
* Hemoglobin ≥ 8 g/dL
* Creatinine ≤ 2.0 mg/dL
* Total bilirubin normal (grade 0)
* No specific limit of total serum bilirubin for patient receiveing indinavir or atazanavir therapy AND direct serum bilirubin ≤ 30% of total bilirubin
* AST and ALT ≤ 2.5 times upper limit of normal (grade 1)
* INR and aPTT normal
* Proteinuria \< 2+
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective barrier contraception during and for up to 3 months after completion of study treatment
* Capable of complying with the study, in the opinion of the investigator
* No acute, active opportunistic infection (other than oral thrush or genital herpes) within the past 14 days
* No other concurrent neoplasia requiring cytotoxic therapy
* No history of any of the following:
* Myocardial infarction
* Severe/unstable angina
* Coronary/peripheral artery bypass graft
* Symptomatic congestive heart failure
* Cerebrovascular accident
* Transient ischemic attack
* Pulmonary embolism
* Deep vein thrombosis
* Other significant thromboembolic event
* No known coagulopathy or bleeding diathesis
* No history of CNS, pulmonary, GI, or urinary bleeding
* No known history of drug-induced liver injury
* Resting systolic blood pressure ≤ 160 mm Hg or diastolic blood pressure ≤ 100 mm Hg
* No history of or ongoing clinically significant illness, medical condition, surgical history, physical finding, ECG finding, or laboratory abnormality that, in the opinion of the investigator, could affect the safety of the patient, alter the absorption of the study drug, or impair the assessment of study results
PRIOR CONCURRENT THERAPY:
* More than 4 weeks since prior and no other concurrent anti-neoplastic therapy for KS, including chemotherapy, radiotherapy, local therapy, or biological therapy
* More than 60 days since prior local therapy for any KS-indicator lesion unless the lesion has clearly progressed since treatment
* Any prior local therapy for indicator lesions (regardless of the elapsed time) should not be allowed unless there is evidence of clear-cut progression of that lesion
* More than 28 days since prior and no other concurrent investigational drugs or therapy (other than antiretroviral therapy or agents available on a treatment IND)
* More than 30 days since prior major surgery and recovered
* More than 14 days since prior treatment for an acute infection (other than oral thrush or genital herpes) or other serious medical illness
* No concurrent surgical procedures
* No concurrent systemic corticosteroid therapy, other than replacement doses
* No concurrent anticoagulant therapy, including warfarin, heparin (including low molecular weight heparin), or antiplatelet drugs (e.g., clopidogrel bisulfate)
* Concurrent aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) allowed provided the dose does not exceed the maximum recommended dose
18 Years
120 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Cancer Institute (NCI)
NIH
PTC Therapeutics
INDUSTRY
The Emmes Company, LLC
INDUSTRY
AIDS Malignancy Consortium
NETWORK
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Susan E. Krown, MD
Role: STUDY_CHAIR
Memorial Sloan Kettering Cancer Center
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Rebecca and John Moores UCSD Cancer Center
La Jolla, California, United States
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States
UCLA Clinical AIDS Research and Education (CARE) Center
Los Angeles, California, United States
Cancer Research Center of Hawaii
Honolulu, Hawaii, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Floyd and Delores Jones Cancer Institute at Virginia Mason Medical Center
Seattle, Washington, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Bender Ignacio RA, Lee JY, Rudek MA, Dittmer DP, Ambinder RF, Krown SE; AIDS Malignancy Consortium (AMC)-059 Study Team. Brief Report: A Phase 1b/Pharmacokinetic Trial of PTC299, a Novel PostTranscriptional VEGF Inhibitor, for AIDS-Related Kaposi's Sarcoma: AIDS Malignancy Consortium Trial 059. J Acquir Immune Defic Syndr. 2016 May 1;72(1):52-7. doi: 10.1097/QAI.0000000000000918.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
CDR0000596565
Identifier Type: OTHER
Identifier Source: secondary_id
PTC299-ONC-005-KS
Identifier Type: OTHER
Identifier Source: secondary_id
AMC-059
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.