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TTAC-0001 and Pembrolizumab Combination phase1b Trial in Recurrent Glioblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03722342
Recruitment Status : Active, not recruiting
First Posted : October 26, 2018
Last Update Posted : January 14, 2020
Sponsor:
Information provided by (Responsible Party):
PharmAbcine

Tracking Information
First Submitted Date  ICMJE July 3, 2018
First Posted Date  ICMJE October 26, 2018
Last Update Posted Date January 14, 2020
Actual Study Start Date  ICMJE January 16, 2019
Actual Primary Completion Date November 4, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 24, 2018)
  • Dose limiting toxicities [ Time Frame: During the first cycle (every cycle is 21 days) of treatment ]
    The frequency and percentage of DLT will be presented by dose level
  • Adverse events [ Time Frame: From the screening visit to the end of treatment visit (time of progressive disease or 2 years) ]
    The frequency and percentage of AEs will be presented by dose level
  • Immunogenicity [ Time Frame: From screening visit to end of treatment visit (time of progressive disease or 2 years) ]
    Presence anti-drug antibody (ADA) will be listed
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2018)
  • Overall response rate [ Time Frame: At every 2nd cycles until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years (every cycle is 21 days) ]
    complete response (CR) or partial response (PR) by RANO criteria
  • Disease control rate [ Time Frame: At every 2nd cycles until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years (every cycle is 21 days) ]
    complete response (CR), partial response (PR) or stable disease (SD) by RANO criteria
  • Progression free survival [ Time Frame: From screening visit to end of treatment visit (time of progressive disease or 2 years) ]
    Period from the date of the drug administration to the disease progression time point
  • Overall survival [ Time Frame: From screening visit to date of patient's death (assessed up to 2 year after end of treatment visit) ]
    Period from the date of the drug administration to the patient's death
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: October 24, 2018)
  • Pharmacokinetic parameters - Cmax [ Time Frame: From screening visit to end of treatment visit (time of progressive disease or 2 years) ]
    Maximum concentration of drug by dose level
  • Pharmacokinetic parameters - Cmin [ Time Frame: From screening visit to end of treatment visit (time of progressive disease or 2 years) ]
    Minimum concentration of drug by dose level
  • Pharmacokinetic parameters - AUC0-t [ Time Frame: From screening visit to end of treatment visit (time of progressive disease or 2 years) ]
    Area under the curve from baseline to each timepoint by dose level
  • Pharmacokinetic parameters - Tmax [ Time Frame: From screening visit to end of treatment visit (time of progressive disease or 2 years) ]
    Time of Cmax by dose level
  • Pharmacokinetic parameters - CL [ Time Frame: From screening visit to end of treatment visit (time of progressive disease or 2 years) ]
    Clearance by dose level
  • Pharmacokinetic parameters - Vd [ Time Frame: From screening visit to end of treatment visit (time of progressive disease or 2 years) ]
    Volume of distribution by dose level
  • Pharmacokinetic parameters - Ke [ Time Frame: From screening visit to end of treatment visit (time of progressive disease or 2 years) ]
    Elimination rate constant by dose level
  • Pharmacokinetic parameters - T½ [ Time Frame: From screening visit to end of treatment visit (time of progressive disease or 2 years) ]
    Half-life by dose level
  • Change in concentration of serum angiogenic factor or receptor [ Time Frame: From screening visit to end of treatment visit (time of progressive disease or 2 years) ]
    VEGF, placental growth factor [PLGF], soluble vascular endothelial growth factor receptor [sVEGFR]-2, sVEGFR-1, etc.
  • DCE-MRI [ Time Frame: From screening visit to end of treatment visit (time of progressive disease or 2 years) ]
    Blood flow parameter - iAUC, K-trans
  • PD-L1, VEGFR-2 expression level [ Time Frame: From screening visit to end of treatment visit (time of progressive disease or 2 years) ]
    PD-L1, VEGFR-2 expression level in tumour environment such as tumour, tumour vessel and parenchymal tissue
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE TTAC-0001 and Pembrolizumab Combination phase1b Trial in Recurrent Glioblastoma
Official Title  ICMJE A Phase 1b, Open-Label, Safety and Tolerability Study of TTAC-0001 in Combination With Pembrolizumab in Patients With Recurrent Glioblastoma
Brief Summary This is a phase 1b, open-Label clinical trial to determine the safety and tolerability and to establish a preliminary recommended Phase 2 dose (RP2D) of TTAC-0001 administered in combination with pembrolizumab in patients with recurrent glioblastoma.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Sequential Assignment
Intervention Model Description:
This was mTPI design to start with optimal dose and next dose level is selected accroding to DLT occurrance
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Recurrent Glioblastoma
Intervention  ICMJE Drug: TTAC-0001 and pembrolizumab combination
  • Investigational product (IP): TTAC-0001 and Pembrolizumab (Merck, Keytruda®)
  • Treatment groups: 3 dose levels

    • Dose level 1 (optimal starting dose): TTAC-0001 12 mg/kg on D1, D8 and D15 + Pembrolizumab 200 mg on D1
    • Dose level 2 (first escalation dose): TTAC-0001 16 mg/kg on D1, D8 and D15 + Pembrolizumab 200 mg on D1
    • Dose level 0 (de-escalation dose): TTAC-0001 8 mg/kg on D1, D8 and D15 + Pembrolizumab 200 mg on D1
  • Cycle: 3 weeks (21 days per cycle)
Study Arms  ICMJE Experimental: TTAC-0001 and pembrolizumab
TTAC-0001 and pembrolizumab combination therapy will be administered.
Intervention: Drug: TTAC-0001 and pembrolizumab combination
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 12, 2020)
9
Original Estimated Enrollment  ICMJE
 (submitted: October 24, 2018)
20
Estimated Study Completion Date  ICMJE April 30, 2020
Actual Primary Completion Date November 4, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Diagnosed with primary glioblastoma by histopathological examination and confirmed recurrent glioblastoma by magnetic resonance imaging (MRI) scans after completing standard of care (Stupp protocol) concomitant temozolomide chemotherapy with radiotherapy (CCRT)
  2. At least one confirmed measurable lesion by RANO criteria
  3. Karnofsky Performance Status (KPS) ≥80
  4. A person who satisfies the following criteria in haematologic, renal, and hepatic function tests performed within 7 days prior to screening:

    1. Haematologic tests

      • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
      • Platelets ≥ 100 x 109/L
      • Haemoglobin ≥ 9.0 g/dL
    2. Blood coagulation tests

      • Prothrombin time (PT) ≤ 1.5 x Upper limit of normal (ULN)
      • Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
    3. Hepatic function tests

      • Total bilirubin ≤ 1.5 x UNL
      • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN in case of liver metastasis)
    4. Renal function test

      • ≤1.5 × ULN or creatinine clearance (CrCl) ≥30 mL/min for patient with creatinine levels >1.5 × institutional ULN
  5. At least 12 weeks of expected survival time
  6. The patient (or legally acceptable representative if applicable) is able and willing to provide written informed consent for the trial

Exclusion Criteria:

  1. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. (Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ [e.g., breast carcinoma, cervical cancer in situ] controlled by curative therapy are not excluded)
  2. Has received prior radiotherapy within 2 weeks of start of study treatment. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease
  3. Has a history of (non-infectious) pneumonitis/interstitial lung diseases that required steroids or current pneumonitis/interstitial lung disease
  4. Has an active infection requiring systemic therapy
  5. Uncontrolled hypertension (systolic blood pressure [SBP]> 150 or diastolic blood pressure [DBP]> 90 mmHg)
  6. Uncontrolled seizures
  7. Class III or IV heart failure by New York Heart Association (NYHA) classification
  8. Has oxygen-dependent chronic disease
  9. Active psychiatric disorder (schizophrenia, major depressive disorder, bipolar disorder etc.). Treated depression with ongoing antidepressant medication is not an exclusion
  10. History of abdominal fistula or gastrointestinal perforation within 6 months prior to start of study drug
  11. History of serious gastrointestinal haemorrhage within 6 months prior to start of study drug
  12. History of severe arterial thromboembolic event within 12 months of start of study drug
  13. Serious grade 4 venous thromboembolic event including pulmonary embolism
  14. History of hypertensive crisis or hypertensive encephalopathy
  15. History of posterior reversible encephalopathy syndrome
  16. Planned surgery within 4 weeks post last dose
  17. Moderate to severe proteinuria as demonstrated by urine dipstick for proteinuria ≥2+. For patients with ≥2+ proteinuria on dipstick urinalysis, a urine protein: creatinine (UPC) ratio will be determined, or a 24-hour urine collection will be done. Patients with a UPC ratio <1 or a 24-hour urine protein <1 gram are eligible
  18. Requiring therapeutic anticoagulation with warfarin at baseline; patients must be off warfarin or warfarin-derivative anticoagulants for at least 7 days prior to starting study drug; however, therapeutic or prophylactic therapy with low-molecular weight heparin is allowed
  19. Not recovered below National Cancer Institute-Common Terminology for Adverse Events (NCI-CTCAE) grade 1 or baseline from AEs due to previous therapy (patient with ≤ Grade 2 neuropathy or alopecia may be eligible)
  20. Treatment with systemic chemotherapy, hormonal therapy, immunotherapy or biologic therapy within 2 weeks prior to the baseline visit
  21. Undergone major surgery requiring general anaesthesia or a respiratory assistance device within 4 weeks prior to the baseline visit (within 2 weeks for video-assisted thoracoscopic surgery [VATS] or open-and-closed [ONC] surgery)
  22. Treated with other investigational drugs within 4 weeks prior to the baseline visit for this study
  23. Pregnant* or lactating females, and females/males of childbearing potential who do not agree to a reliable and adequate method of contraception
  24. A known history of severe drug hypersensitivity or hypersensitivity to a therapy similar to the study drugs
  25. Unable to participate in the trial according to the investigator's decision
  26. Previous therapy with vascular endothelial growth factor (VEGF)-targeted agents including (but not limited to) bevacizumab
  27. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher irAE
  28. Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
  29. Known human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority
  30. Known active hepatitis B or hepatitis C infection. No testing for hepatitis B and hepatitis C is required unless mandated by local health authority
  31. Have received a live vaccine within 30 days prior to enrollment. Seasonal flu vaccines that do not contain live virus are permitted
  32. Have had a serious or non-healing wound, ulcer, or bone fracture within 28 days prior to enrollment
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia
Removed Location Countries Korea, Republic of
 
Administrative Information
NCT Number  ICMJE NCT03722342
Other Study ID Numbers  ICMJE PMC_TTAC-0001_04
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party PharmAbcine
Study Sponsor  ICMJE PharmAbcine
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account PharmAbcine
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP