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Trial record 5 of 5 for:    TG02

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

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ClinicalTrials.gov Identifier: NCT02933944
Recruitment Status : Recruiting
First Posted : October 14, 2016
Last Update Posted : December 19, 2017
Sponsor:
Information provided by (Responsible Party):
Targovax ASA

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 recurrent rectal cancer scheduled to have surgery.

Part I and Part II will include approximately 10 patients each. 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.


Condition or disease Intervention/treatment Phase
Rectal Cancer Biological: TG02-treatment Drug: Pembrolizumab Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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 Recurrent Oncogenic RAS Exon 2 Mutant Rectal Cancer
Study Start Date : September 2016
Estimated Primary Completion Date : December 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
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.

Biological: TG02-treatment Drug: Pembrolizumab



Primary Outcome Measures :
  1. 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 ]
  2. Number of patients with systemic TG02 specific immune response assessed by a Delayed Type Hypersensitivity (DTH) test. [ Time Frame: 8 weeks ]
  3. Systemic immune response assessed as change in presence of TG02 specific T-cells in peripheral blood [ Time Frame: 8 weeks ]
  4. Immunological activation in tumour mass by assessing number of patients with increased intra-tumoural lymphocytes. [ Time Frame: 8 weeks ]

Secondary Outcome Measures :
  1. Change of immune suppression factors e.g. PD-1 and T-reg from pre to post treatment [ Time Frame: 8 weeks ]
  2. Change in pathological responses and markers of apoptosis in tumour tissue [ Time Frame: 8 weeks ]
  3. Changes in standard uptake values (SUV) will be assessed by FDG PET-CT images [ Time Frame: From screening until surgery ]
  4. 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 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with locally recurrent rectal cancer (histologically or cytologically confirmed adenocarcinoma), with a confirmed oncogenic KRAS exon 2, codon 12 or 13 mutations, who are considered suitable for radical resection(R0) (e.g. pelvic exenteration)
  • 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 <1.5 x ULN or Creatinine Clearance ≥ 50ml/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
  • 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 for whom pre-surgery radiotherapy with or without chemotherapy, any other anti-cancer treatment including chemotherapy or localised radiation for severe pain is indicated or planned less than 2 weeks before screening
  • The patient 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, hepatitis B or C
  • Known malignant brain lesion(s)
  • Are planned to receive yellow fever or other live (attenuated) vaccines during the course of study
  • For Part II - any contraindication to receiving pembrolizumab:

Hypersensitivity to the active substance (pembrolizumab) or to any of the excipients; L-histidine, L-histidine hydrochloride monohydrate, Sucrose, Polysorbate 80


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02933944


Contacts
Contact: Karianne Risberg Handeland, PhD +47 900 30 831 karianne.risberg.handeland@targovax.com
Contact: Magnus Jäderberg, MD +447791443820 magnus.jaderberg@targovax.com

Locations
Australia
Royal Brisbane & Women's Hospital (RBWH) Recruiting
Brisbane, Australia
Contact: Matthew Burge, MD         
Peter MacCallum Cancer Centre Recruiting
Melbourne, Australia
Contact: Michael Michael, MD         
Chris O'Brien Lifehouse Recruiting
Sydney, Australia
Contact: Lisa Horvath, MD         
New Zealand
Auckland City Hospital Recruiting
Auckland, New Zealand
Contact: Sanjeev Deva, MD         
Christchurch Hospital Recruiting
Christchurch, New Zealand
Contact: Dean Harris, MD         
Sponsors and Collaborators
Targovax ASA

Responsible Party: Targovax ASA
ClinicalTrials.gov Identifier: NCT02933944     History of Changes
Other Study ID Numbers: CT TG02-01
First Posted: October 14, 2016    Key Record Dates
Last Update Posted: December 19, 2017
Last Verified: December 2017

Keywords provided by Targovax ASA:
locally recurrent

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Pembrolizumab
Antineoplastic Agents