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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02933944




Registration number
NCT02933944
Ethics application status
Date submitted
8/09/2016
Date registered
14/10/2016
Date last updated
14/06/2019

Titles & IDs
Public title
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
Scientific 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 Advanced Primary and Recurrent Oncogenic RAS Exon 2 Mutant Colorectal Cancer
Secondary ID [1] 0 0
CT TG02-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - TG02-treatment
Treatment: Drugs - Pembrolizumab

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.


Other interventions: TG02-treatment


Treatment: Drugs: Pembrolizumab


Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety of TG02-treatment by assessment of laboratory parameters (routine haematology and biochemistry), vital signs and recording of adverse events
Timepoint [1] 0 0
From start of study until End of study, which is approximately 4 weeks after surgery and maximum 20 weeks after start of TG02-treatment
Primary outcome [2] 0 0
Number of patients with systemic TG02 specific immune response assessed by a Delayed Type Hypersensitivity (DTH) test.
Timepoint [2] 0 0
8 weeks
Primary outcome [3] 0 0
Systemic immune response assessed as change in presence of TG02 specific T-cells in peripheral blood
Timepoint [3] 0 0
8 weeks
Primary outcome [4] 0 0
Immunological activation in tumour mass by assessing number of patients with increased intra-tumoural lymphocytes.
Timepoint [4] 0 0
8 weeks
Secondary outcome [1] 0 0
Change of immune suppression factors e.g. PD-1 and T-reg from pre to post treatment
Timepoint [1] 0 0
8 weeks
Secondary outcome [2] 0 0
Change in pathological responses and markers of apoptosis in tumour tissue
Timepoint [2] 0 0
8 weeks
Secondary outcome [3] 0 0
Changes in standard uptake values (SUV) will be assessed by FDG PET-CT images
Timepoint [3] 0 0
From screening until surgery
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
From screening until surgery

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Brisbane & Women's Hospital (RBWH) - Brisbane
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
- Brisbane
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
New Zealand
State/province [2] 0 0
Christchurch

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Targovax ASA
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02933944
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02933944