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Study of TRC105 Combined With Standard-Dose Bevacizumab for Advanced Solid Tumors for Which Bevacizumab is Indicated

7. november 2018 opdateret af: Tracon Pharmaceuticals Inc.

An Open Label Phase 1B Dose-Escalation Study of TRC105 Combined With Standard-Dose Bevacizumab for Advanced Solid Tumors

The purpose of the study is to evaluate safety and tolerability and determine a recommended Phase 2 dose for TRC105 when added to standard dose bevacizumab in patients with advanced solid tumors for which bevacizumab is indicated.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

Bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF) that inhibits angiogenesis and extends survival in patients with a wide variety of solid tumor types. TRC105, a monoclonal antibody to CD105, is a novel angiogenesis inhibitor that complements bevacizumab in preclinical models. Together, these antibodies may result in more effective angiogenesis inhibition and improved clinical efficacy over that seen with bevacizumab alone. The purpose of the study is to evaluate safety and tolerability and determine a recommended Phase 2 dose for TRC105 when added to standard dose bevacizumab in patients with advanced solid tumors for which bevacizumab is indicated.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

38

Fase

  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

    • Alabama
      • Birmingham, Alabama, Forenede Stater, 35249
        • University of Alabama at Birmingham
    • Arizona
      • Scottsdale, Arizona, Forenede Stater, 85258
        • Pinnacle Oncology Hematology
    • California
      • Santa Monica, California, Forenede Stater, 90404
        • UCLA Hematology and Oncology
    • Indiana
      • Indianapolis, Indiana, Forenede Stater, 46202
        • Indiana University Simon Cancer Center

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  1. Histologically proven advanced or metastatic solid cancer
  2. Measurable disease, evaluable disease or elevation of a relevant soluble tumor marker (e.g., CEA, PSA, CA125)
  3. Age of 18 years or older
  4. ECOG performance status of 0 or 1
  5. Resolution of all acute AEs resulting from prior cancer therapies to NCI CTCAE Grade ≤ 1 or baseline (except alopecia)
  6. Adequate organ function
  7. Willing and able to consent for self to participate in study

Exclusion Criteria:

  1. Prior treatment with TRC105
  2. Serious dose-limiting toxicity related to prior bevacizumab
  3. Current treatment on another therapeutic clinical trial
  4. Receipt of an investigational agent within 28 days of starting study treatment
  5. Prior surgery (including open biopsy) within 28 days of starting the study treatment
  6. Prior radiation therapy or systemic therapy within 21 days of starting the study treatment
  7. Minor surgical procedures such as fine needle aspirations, Mediport placement or core biopsies within 7 days of study treatment
  8. Uncontrolled chronic hypertension defined as systolic > 140 or diastolic > 90 despite optimal therapy (initiation or adjustment of BP medication prior to study entry allowed provided that the average of 3 BP readings at a visit prior to enrollment is < 140/90 mm Hg)
  9. Symptomatic pericardial or pleural effusions
  10. Uncontrolled peritoneal effusions requiring paracentesis more frequently than every 2 weeks
  11. History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease (except in the expansion cohort at the MTD where brain metastases or primary brain tumors are eligible)
  12. Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, DVT, PTCA or CABG within the past 6 months
  13. Active bleeding or pathologic condition that carries a high risk of bleeding
  14. Thrombolytic or anticoagulant use (except to maintain i.v. catheters) within 10 days prior to first day of study therapy
  15. Cardiac dysrhythmias of NCI CTCAE Grade ≥ 2 within the last 28 days
  16. Known active viral or nonviral hepatitis
  17. Centrally located non-small cell lung cancer (regardless of histologic sub-type), or non-small cell lung cancer of squamous histology.
  18. History of hemorrhage or hemoptysis (>½ teaspoon bright red blood) within 6 months of starting study treatment
  19. Open wounds or unhealed fractures within 28 days of starting study treatment
  20. History of peptic ulcer disease or erosive gastritis within the past 6 months, unless treated for the condition and complete resolution has been documented by esophagogastroduodenoscopy (EGD) within 28 days of starting study treatment
  21. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
  22. Pregnancy or breastfeeding

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: TRC105 and Bevacizumab
Escalating doses of i.v. TRC105 will be administered weekly beginning with 3 mg/kg in combination with 15 mg/kg bevacizumab given every 3 weeks. Patients will receive TRC105 treatment on Days 1, 8, and 15 and bevacizumab treatment on Day 1 of each 21-day cycle.
Escalating doses of i.v. TRC105 will be administered weekly beginning with 3 mg/kg in combination with 15 mg/kg bevacizumab given every 3 weeks. Patients will receive TRC105 treatment on Days 1, 8, and 15 and bevacizumab treatment on Day 1 of each 21-day cycle.
Andre navne:
  • Avastin
  • Kimært antistof (TRC105) mod CD105

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Determine Maximum Tolerated Dose of TRC105 in Combination With Bevacizumab
Tidsramme: 1.5 years
Three patients will be initially enrolled and treated at each dose level. If none of these 3 patients experiences a dose-limiting toxicity (DLT) during the 28-day evaluation period, dose escalation will proceed following review of safety data with appropriate site staff including the principal investigators at all sites. If 1 of 3 patients experiences DLT, the cohort will be expanded to 6 patients. The maximum tolerated dose (MTD) will have been exceeded if ≥ 33% of patients experience DLT in a given cohort. DLT will have occurred when a patient has 1 or more toxicity listed in the table below that is at least possibly related to the combination of bevacizumab and TRC105 during the first 28 days (cycle 1).
1.5 years

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
TRC105 Pharmacokinetic Concentrations
Tidsramme: 1.5 years
Plasma TRC105 concentrations will be measured at specified timepoints.
1.5 years
Immune Response to TRC105
Tidsramme: 1.5 years
HAMA and HACA titers will be measured at specified time-points.
1.5 years
Objective Response According to RECIST 1.1
Tidsramme: 1.5 years
The best response according to RECIST 1.1 for each patient with measurable disease and who received at least one dose of study drug will be listed by cohort and tumor type
1.5 years

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Efterforskere

  • Studieleder: Charles P Theuer, MD, Tracon Pharmaceuticals Inc.

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. april 2011

Primær færdiggørelse (Faktiske)

1. september 2012

Studieafslutning (Faktiske)

1. december 2013

Datoer for studieregistrering

Først indsendt

7. april 2011

Først indsendt, der opfyldte QC-kriterier

8. april 2011

Først opslået (Skøn)

11. april 2011

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

5. december 2018

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

7. november 2018

Sidst verificeret

1. november 2018

Mere information

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Voksen fast tumor

Kliniske forsøg med TRC105 and Bevacizumab

3
Abonner