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Trial record 3 of 6 for:    Targovax

Exploratory Study of TG02-treatment as Monotherapy or in Combination With Pembrolizumab to Assess Safety and Immune Activation in Patients With Locally Advanced Primary and Recurrent Oncogenic RAS Exon 2 Mutant Colorectal Cancer

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ClinicalTrials.gov Identifier: NCT02933944
Recruitment Status : Terminated (Changing priorities)
First Posted : October 14, 2016
Last Update Posted : June 14, 2019
Sponsor:
Information provided by (Responsible Party):
Targovax ASA

Tracking Information
First Submitted Date  ICMJE September 8, 2016
First Posted Date  ICMJE October 14, 2016
Last Update Posted Date June 14, 2019
Study Start Date  ICMJE September 2016
Actual Primary Completion Date February 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 17, 2016)
  • Safety of TG02-treatment by assessment of laboratory parameters (routine haematology and biochemistry), vital signs and recording of adverse events [ Time Frame: From start of study until End of study, which is approximately 4 weeks after surgery and maximum 20 weeks after start of TG02-treatment ]
  • Number of patients with systemic TG02 specific immune response assessed by a Delayed Type Hypersensitivity (DTH) test. [ Time Frame: 8 weeks ]
  • Systemic immune response assessed as change in presence of TG02 specific T-cells in peripheral blood [ Time Frame: 8 weeks ]
  • Immunological activation in tumour mass by assessing number of patients with increased intra-tumoural lymphocytes. [ Time Frame: 8 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 13, 2016)
  • To determine the safety of TG02-treatment by assessment of laboratory parameters (routine haematology and biochemistry), vital signs and recording of adverse events [ Time Frame: From start of study until End of study, which is approximately 4 weeks after surgery and maximum 20 weeks after start of TG02-treatment ]
  • To determine number of patients with systemic TG02 specific immune response assessed by a Delayed Type Hypersensitivity (DTH) test. [ Time Frame: 8 weeks ]
  • To determine systemic immune response assessed as change in presence of TG02 specific T-cells in peripheral blood [ Time Frame: 8 weeks ]
  • To determine immunological activation in tumour mass by assessing number of patients with increased intra-tumoural lymphocytes. [ Time Frame: 8 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 13, 2016)
  • Change of immune suppression factors e.g. PD-1 and T-reg from pre to post treatment [ Time Frame: 8 weeks ]
  • Change in pathological responses and markers of apoptosis in tumour tissue [ Time Frame: 8 weeks ]
  • Changes in standard uptake values (SUV) will be assessed by FDG PET-CT images [ Time Frame: From screening until surgery ]
  • Changes in the tumour marker Carcinoembryonic Antigen (CEA) throughout treatment will be assessed by analysis of blood samples to follow the evolution of disease under treatment [ Time Frame: From screening until surgery ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Exploratory Study of TG02-treatment as Monotherapy or in Combination With Pembrolizumab to Assess Safety and Immune Activation in Patients With Locally Advanced Primary and Recurrent Oncogenic RAS Exon 2 Mutant Colorectal Cancer
Official Title  ICMJE A Non-Randomised Open-Label Phase Ib Exploratory Study of TG02-treatment as Monotherapy or in Combination With Pembrolizumab to Assess Safety and Immune Activation in Patients With Locally Advanced Primary and Recurrent Oncogenic RAS Exon 2 Mutant Colorectal Cancer
Brief Summary

The purpose of this study is to determine safety and anti-tumor immune activation generated by TG02 and Granulocyte macrophage colony stimulating factor (GM-CSF), first as monotherapy (Part I), thereafter in combination with the checkpoint inhibitor pembrolizumab (Part II), in patients with locally advanced primary and recurrent colorectal cancer scheduled to have surgery.

Part I will include 4-6 patients and Part II will include up to 10 patients. Part I and Part II are separate and independent sequential components of the study. Patients will only be able to participate in either the Part I cohort or Part II cohort.

Main objective of the study is to investigate safety and immune response after TG02-treatment.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Rectal Cancer
Intervention  ICMJE
  • Biological: TG02-treatment
  • Drug: Pembrolizumab
Study Arms  ICMJE Experimental: TG02-treatment

Part I: The TG02-treatment consists of an intradermal injection of GM-CSF followed by an injection of TG02. The GM-CSF is to be given 15-30 minutes before TG02. TG02-treatment will be administered on Days 1, 8, 15, 22 and 36. If surgery after week 10, TG02-treatment will also be given at week 10 (Day 64).

Part II: TG02-treatment will be given as described under Part I. In addition pembrolizumab will be administered.

Interventions:
  • Biological: TG02-treatment
  • Drug: Pembrolizumab
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 Terminated
Actual Enrollment  ICMJE
 (submitted: June 13, 2019)
6
Original Estimated Enrollment  ICMJE
 (submitted: October 13, 2016)
20
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date February 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with locally advanced primary and recurrent colorectal cancer (CRC) (histologically or cytologically confirmed adenocarcinoma), with a confirmed oncogenic KRAS exon 2, codon 12 or 13 mutations, eligible for radical pelvic surgery at time of enrolment.
  • Patient is ≥18 years of age and able to consent
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
  • Patient has adequate organ and bone marrow function within 28 days of study

    • Neutrophil count >1.5 x10^9/L
    • Platelets >100 x10^9/L
    • Hb >90g/L
    • Total bilirubin <1.5 upper limit of normal, ULN
    • ALT and AST <3.0 x ULN
    • Serum creatinine <3 x ULN or Creatinine Clearance ≥ 30ml/min (Cockroft-Gault or Nuclear GFR method)
    • PT and APTT <1.3 x ULN
  • The patient is willing to provide study specific pre TG02-treatment biopsy of tumour mass and allow use of archival tumour biopsies. For patients where there are technical reasons a baseline biopsy cannot be performed but who fulfil all the other inclusion criteria, the investigator shall contact the medical monitor to discuss the possibility of including such patient.
  • The patient is willing and able to comply with the protocol, and agrees to return to the hospital for study visits and examinations
  • Men and women of childbearing potential must use adequate contraception to prevent pregnancy during the study. Adequate contraception is defined in the study as any medically recommended method (or combination of methods) as per standard of care. An adequate contraception includes hormonal contraception with implants or combined oral, transdermal or injectable contraceptives, certain intrauterine devices, bilateral tubal ligation, hysterectomy, or vasectomy of partner. A combination of male condom with either cap, diaphragm or sponge with spermicide are also considered acceptable. For women of childbearing potential a negative pregnancy test needs to be confirmed before inclusion.
  • The patient has been fully informed about the study and is willing to participate in the study, and has provided written informed consent form prior to any trial specific screening procedures.

Exclusion Criteria:

  • The patient has previously received an anticancer vaccine or immune checkpoint inhibitor, or participated in a trial involving the use of an anticancer vaccine or immune checkpoint inhibitor
  • Patients where pre-surgery radiotherapy, chemotherapy or other anti-cancer therapy has not been completed ≥ 2 weeks prior to TG02-treatment
  • The patients is receiving anti-cancer therapy for concurrent illness
  • The patient has had a prior different malignancy within the last 3 years (excluding adequately treated basal cell or squamous cell carcinoma of the skin cancer, or localised low grade tumours considered cured and not requiring systemic therapy)
  • The patient has uncontrolled or significant intercurrent or recent illness including:

    • auto-immune disorder or history of autoimmune disease requiring immunosuppressive treatment.
    • cardiac disorder such as uncontrolled cardiac failure, unstable angina or non-ST segment elevation myocardial infarction (NSTEMI) or myocardial infarction, uncontrolled arrhythmia less than 3 months before screening
    • stroke or thromboembolic event within 3 months of study commencement
    • active or uncontrolled severe infection
    • history of solid organ transplantation or any condition requiring chronic treatment with corticosteroids or other immunosuppressive agents
    • active coagulopathy/bleeding diathesis
    • cirrhosis, chronic active or untreated persistent hepatitis
    • history of adverse reactions to peptide vaccines
  • The patient is pregnant or lactating.
  • Has received an investigational drug within 4 weeks prior to study drug administration, or unless other has been agreed with the medical monitor
  • Is currently receiving any agent with a known effect on the immune system, unless at dose levels that are not immunosuppressive (e.g. prednisone at 10 mg/day or less or as inhaled steroid at doses used for the treatment of asthma)
  • Known history of positive tests for HIV/AIDS
  • Are planned to receive yellow fever or other live (attenuated) vaccines during the course of study
  • For Part II - any contraindication to receiving pembrolizumab:

If using the 50 mg lyophilized powder; hypersensitivity to the active substance (pembrolizumab) or to any of the excipients; L-histidine, L-histidine hydrochloride monohydrate, Sucrose, Polysorbate 80.

If using the 100 mg concentrate; hypersensitivity to the active substance (pembrolizumab) or to any of the excipients; L-histidine, Sucrose, Polysorbate 80

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,   New Zealand
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02933944
Other Study ID Numbers  ICMJE CT TG02-01
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Targovax ASA
Study Sponsor  ICMJE Targovax ASA
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Targovax ASA
Verification Date June 2019

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