Rectal CancerPhase 1NCT02933944
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
A Phase 1 study testing TG02-treatment and Pembrolizumab in people with Rectal Cancer, run by Targovax ASA at 4 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- TG02-treatment and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Sep 2016to Sep 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Australia2 sites
Royal Brisbane & Women's Hospital (RBWH)
Brisbane
Peter MacCallum Cancer Centre
Melbourne
New Zealand2 sites
Auckland City Hospital
Auckland
Christchurch Hospital
Christchurch
About this study
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 Advanced Primary and Recurrent Oncogenic RAS Exon 2 Mutant Colorectal Cancer
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.
- Conditions
- Rectal Cancer
- Being tested
- TG02-treatment, Pembrolizumab
- Keywords
- locally recurrent
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TG02-treatmentBiological
PembrolizumabDrug
| Study group | Role | What they receive |
|---|---|---|
| TG02-treatment | Experimental | 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. Receives: Biological: TG02-treatment; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patients Safety During Study
Safety of TG02-treatment by assessment of laboratory parameters (routine haematology and biochemistry), vital signs and recording of adverse events
Measured: From start of study until End of study, which is approximately 4 weeks after surgery and maximum 20 weeks after start of TG02-treatment
Patients' Immune Response Assessed by Delayed Type Hypersensitive (DTH) Test
Number of patients with systemic TG02 specific immune response assessed by a Delayed Type Hypersensitivity (DTH) test
Measured: 8 weeks
Systemic Immune Response: T-cell Response
Systemic immune response assessed as change in presence of TG02 specific T-cells in peripheral blood
Measured: 8 weeks
Immunological Activation in Tumour Mass by Assessing Number of Patients With Increased Intra-tumoural Lymphocytes.
Immunological activation in tumour mass by assessing fold changes from baseline of intra-tumoural lymphocytes.
Measured: 8 weeks
Secondary outcomes (4)
Change of Immune Suppression Factors e.g. PD-1 and T-reg From Pre to Post Treatment
Number of patients with changes from baseline in immune suppression factors (such as PDL1, Treg and MSDC) from tumour samples collected pre TG02/GMCSF treatment
Measured: 8 weeks
Change in Pathological Responses and Markers of Apoptosis in Tumour Tissue
Measured: 8 weeks
Changes in Standard Uptake Values (SUV) Will be Assessed by FDG PET-CT Images
Measured: 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
Measured: From screening until surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2016 (estimated)
- Study startSep 2016
- Primary completionFeb 2019
- Study completionSep 2019
Why it stopped: Changing priorities
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Rectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Targovax ASA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02933944
- Sponsor's protocol ID
- CT TG02-01
- Status last verified
- Jun 2019
- First submitted
- 8 Sep 2016
- Last updated
- 26 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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 Advanced Primary and Recurrent Oncogenic RAS Exon 2 Mutant Colorectal Cancer
- ClinicalTrials.gov ID
- NCT02933944
- Acronym / sponsor ID
- CT TG02-01
- Conditions
- Rectal Cancer
- Keywords
- locally recurrent
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Changing priorities
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Targovax ASAIndustry (pharma, biotech, devices)
- Study start
- Sep 2016
- Primary completion
- Feb 2019 (actual)
- Study completion
- Sep 2019 (actual)
- First posted
- 14 Oct 2016 (estimated)
- Results
- Posted 26 Jan 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TG02-treatment | Experimental | Biological: TG02-treatment, Drug: PembrolizumabPart 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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
- 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.
Key exclusion criteria (21 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TG02-treatment | Biological | TG02-treatment |
| Pembrolizumab | Drug | TG02-treatment |
Primary outcome
Patients Safety During Study
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
Safety of TG02-treatment by assessment of laboratory parameters (routine haematology and biochemistry), vital signs and recording of adverse events
Patients' Immune Response Assessed by Delayed Type Hypersensitive (DTH) Test
Time frame: 8 weeks
Number of patients with systemic TG02 specific immune response assessed by a Delayed Type Hypersensitivity (DTH) test
Systemic Immune Response: T-cell Response
Time frame: 8 weeks
Systemic immune response assessed as change in presence of TG02 specific T-cells in peripheral blood
Immunological Activation in Tumour Mass by Assessing Number of Patients With Increased Intra-tumoural Lymphocytes.
Time frame: 8 weeks
Immunological activation in tumour mass by assessing fold changes from baseline of intra-tumoural lymphocytes.
4 secondary outcomes
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TG02-treatment and Pembrolizumab in people with Rectal Cancer, run by Targovax ASA at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Australia, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patients Safety During Study (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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2022.