Breast Cancer FemalePhase 1TMBANCT03788083
Intratumoral TriMix Injections in Early Breast Cancer Patients
A Phase 1 study testing Trimix in people with Breast Cancer Female and Early-stage Breast Cancer, run by Universitair Ziekenhuis Brussel at 1 site in Belgium.
Trial summary
Patients with early breast cancer and accessible tumor lesions (1.00 to 10 ml volume) that are eligible to either surgical removal of their tumor or neoadjuvant chemotherapy will be injected with the IMP. Read more about this study
- Who is it for?
- Ages 18 to 85 years, women only
- Conditions the study is for
- Breast Cancer Female, Early-stage Breast Cancer
- What is being tested?
- Trimix
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteBelgium
- Study dates
- 12 Nov 2018to 30 Dec 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 to 85 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age greater than or equal to 18 years and less than or equal to 85 yrs
- Histologically proven breast cancer eligible for curative surgery (with or without the need for neoadjuvant chemotherapy) with one or more injection-accessible (allowing ultrasound guidance) nodal tumors.
- Injectable tumor lesions must have a volume between 1.00 and 10 ml, only one lesion per patient will be injected
- ECOG performance status of 0 or 1
- Willing to give informed consent in writing
- Willing and able to attend the scheduled study visits and to comply with the study procedures
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- No prior therapy for ipsilateral breast cancer
- Normal lab parameters: white cell count ≥ 3,000/mm3, hemoglobin ≥ 10mg/dl, platelet count ≥ 100,000/mm3, serum creatinine ≤ 1.5 x institutional ULN, bilirubin ≤ 2.0 mg/dl aspartate aminotransferase/alanine aminotransferase/ alkaline phosphatase ≤ 2 x the upper normal limit (AST< 72 U/l, ALT < 104 U/l, AP < 252 U/l)
- Adequate Coagulation Parameters with: Prothrombin INR < 1.5; Partial Thromboplastin Time < 1.5 x 34.4 sec (51.6 sec)
- Female patients of childbearing potential should have a negative serum pregnancy test at screening visit and should use a highly efficient method of birth control for the duration of treatment and until the first menses after a 4 week period after the last dose of study medication. Highly effective birth control methods include:
- combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation administered oral, intravaginal or transdermal.
- progestogen-only hormonal contraception associated with inhibition of ovulation administered oral, as an injectable or implantable formulation.
- intrauterine device
- intrauterine hormone-releasing system
- bilateral tubal occlusion
- vasectomised partner
- abstinence from sexual intercourse
Who cannot join
- Male patients
- Patients with stage III-IV breast cancer (AJCC 8th edition)
- Patients with highly vascularized tumor or important post-biopsy hematoma
- Previous chemotherapy for breast cancer or other types of cancer within the last five years
- Other malignancies other than non-melanoma skin cancer, or controlled superficial bladder cancer. In the event of prior malignancies treated surgically, the patient must be considered NED (no evidence of disease) for a minimum of 3 years prior to enrolment
- Patients with a history of autoimmune disease (inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, rheumatoid arthritis or multiple sclerosis) other auto-immune or debilitating diseases. Vitiligo is not an exclusion criterion.
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- Patients with serious intercurrent chronic or acute illness such as pulmonary [asthma or chronic obstructive pulmonary disease (COPD)] or cardiac (NYHA class III or IV) or hepatic disease or other illness considered by the P.I. to constitute an unwarranted high risk for investigational drug treatment
- Patients with significant psychiatric disabilities or seizure disorders
- Legal incapacity or limited legal capacity
- Patients on steroid therapy > 10 mg prednisone (or equivalent) or other immunosuppressive agents such as azathioprine or cyclosporine A are excluded on the basis of potential immune suppression. Patients must have had 8 weeks of discontinuation of any steroid therapy exceeding > 10 mg prednisone (or equivalent) prior to enrolment
- Presence of an active acute or chronic infection, including symptomatic urinary tract infection, HIV (as determined by ELISA and confirmed by Western Blot) or viral hepatitis (as determined by HBsAg and Hepatitis C serology)
- Patient is pregnant or is currently breast-feeding
Trial locations and contacts
1 site in 1 country.
Belgium1 site, 1 recruiting
- Recruiting
UZ Brussel
Jette, Brussels Capital, 1090
UZ Brussel, +32 2 477 6015, borstkliniek@uzbrussel.be
Marian Vanhoeij, MD
About this study
Official title: A Phase I Study on the Safety and Immune-modulatory Effect of Intratumoral (i.t.) Administration of mRNA (Messenger RNA) Encoding Dendritic Cell Activating Proteins in Patients With Early, Resectable Breast Cancer
Patients with early breast cancer and accessible tumor lesions (1.00 to 10 ml volume) that are eligible to either surgical removal of their tumor or neoadjuvant chemotherapy will be injected with the IMP. Patients will be either treated with placebo (buffer alone, 12 patients) or with TriMix mRNA at three dose levels [8 at dose level I (1mg/ml), 8 at dose level II (3mg/ml), and 8 at dose level III (6mg/ml). The volume injected in this group will be adjusted to the tumour volume to ensure a perfusion of around 33% of the tumour volume (33% +/- 5%). Therefore, depending on the patients' tumour size, 500, 1000 or 2000 µl of TriMix mRNA solution or placebo solution will be injected into each tumor. Each patient will receive three administrations of TriMix prior to start of general treatment (surgery or neoadjuvant chemotherapy) separated by one week (7 days +/- 2 days) interval. The last administration will be performed 2 days preoperatively or start of neoadjuvant chemotherapy.
The tumor and peripheral blood samples will be analyzed for immunological changes. If it is decided by the multidisciplinary team that neoadjuvant therapy is more appropriate for the patient, a second tumor biopsy (instead of surgical resection) will be taken 2 days after third administration of TriMix mRNA to assess immunological changes within the tumor. Similarly, patients that refuses to undergo surgery or to receive neoadjuvant chemotherapy can be enrolled into the trial, if they accept three administrations of TriMix followed by a second tumor biopsy.
The study will start with recruitment of the placebo group. The enrollment of the first three patients in each cohort with Trimix mRNA will be staggered with at least one day between the first dose of each individual patient. One week after the third patient of a cohort received the third TriMix mRNA administration, an overall evaluation of the safety and tolerability of this cohort will be done by the principal investigator. The results will be reviewed by an in-house dose evaluation committee overseeing the safety and tolerability of TriMix mRNA.
- Conditions
- Breast Cancer Female, Early-stage Breast Cancer
- Being tested
- Trimix, Placebo
- Keywords
- immune therapy, dendritic cells, immune priming
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrimixDrug
Intratumoral TriMix injection
PlaceboDrug
Intratumoral placebo injection
| Study group | Role | What they receive |
|---|---|---|
| placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| TriMix | Active comparator | Not described Receives: Drug: Trimix |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Number of patients with adverse events, total number of adverse events, dose limiting toxicities
Measured: 2 years
Secondary outcomes (3)
Tumor microenvironment changes induced by intratumoral TriMix mRNA
Tumor microenvironment changes induced by intratumoral TriMix mRNA administration from diagnostic biopsy to day 21 (visit 5) assessed by immunohistochemistry.
Measured: 30 days
Tumor microenvironment changes induced by intratumoral TriMix mRNA
Tumor microenvironment changes induced by intratumoral TriMix mRNA administration from diagnostic biopsy to day 21 (visit 5) assessed by nanoString gene profiling
Measured: 30 days
TriMix mRNA induced T-cell responses
TriMix mRNA induced T-cell responses assessed by immunoassays in situ and in peripheral blood
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2018
- Study start12 Nov 2018
- Primary completion30 Sep 2024 (estimated)
- Study completion30 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast Cancer FemaleStudies of the same condition, open and under way.
- More trials run by Universitair Ziekenhuis BrusselThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universitair Ziekenhuis Brussel
- Sponsor type
- University, hospital or other
- Collaborators
- eTheRNA immunotherapies
- Responsible party
- Sponsor
- Investigators
- Marian Vanhoeij, MD, Principal investigator, Universitair Ziekenhuis Brussel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03788083
- Sponsor's protocol ID
- TriMix-Breast
- Acronym
- TMBA
- Status last verified
- May 2022
- First submitted
- 16 Nov 2018
- Last updated
- 19 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study on the Safety and Immune-modulatory Effect of Intratumoral (i.t.) Administration of mRNA (Messenger RNA) Encoding Dendritic Cell Activating Proteins in Patients With Early, Resectable Breast Cancer
- ClinicalTrials.gov ID
- NCT03788083
- Acronym / sponsor ID
- TMBA / TriMix-Breast
- Conditions
- Breast Cancer Female, Early-stage Breast Cancer
- Keywords
- immune therapy, dendritic cells, immune priming
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Universitair Ziekenhuis BrusselUniversity, hospital or other
- Collaborators
- eTheRNA immunotherapies
- Study start
- 12 Nov 2018 (actual)
- Primary completion
- 30 Sep 2024 (estimated)
- Study completion
- 30 Dec 2024 (estimated)
- First posted
- 27 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with early breast cancer and accessible tumor lesions (1.00 to 10 ml volume) that are eligible to either surgical removal of their tumor or neoadjuvant chemotherapy will be injected with the IMP. Patients will be either treated with placebo (buffer alone, 12 patients) or with TriMix mRNA at three dose levels [8 at dose level I (1mg/ml), 8 at dose level II (3mg/ml), and 8 at dose level III (6mg/ml). The volume injected in this group will be adjusted to the tumour volume to ensure a perfusion of around 33% of the tumour volume (33% +/- 5%). Therefore, depending on the patients' tumour size, 500, 1000 or 2000 µl of TriMix mRNA solution or placebo solution will be injected into each tumor. Each patient will receive three administrations of TriMix prior to start of general treatment (surgery or neoadjuvant chemotherapy) separated by one week (7 days +/- 2 days) interval. The last administration will be performed 2 days preoperatively or start of neoadjuvant chemotherapy.
The tumor and peripheral blood samples will be analyzed for immunological changes. If it is decided by the multidisciplinary team that neoadjuvant therapy is more appropriate for the patient, a second tumor biopsy (instead of surgical resection) will be taken 2 days after third administration of TriMix mRNA to assess immunological changes within the tumor. Similarly, patients that refuses to undergo surgery or to receive neoadjuvant chemotherapy can be enrolled into the trial, if they accept three administrations of TriMix followed by a second tumor biopsy.
The study will start with recruitment of the placebo group. The enrollment of the first three patients in each cohort with Trimix mRNA will be staggered with at least one day between the first dose of each individual patient. One week after the third patient of a cohort received the third TriMix mRNA administration, an overall evaluation of the safety and tolerability of this cohort will be done by the principal investigator. The results will be reviewed by an in-house dose evaluation committee overseeing the safety and tolerability of TriMix mRNA.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| placebo | Placebo comparator | Drug: Placebo |
| TriMix | Active comparator | Drug: Trimix |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Age greater than or equal to 18 years and less than or equal to 85 yrs
- Histologically proven breast cancer eligible for curative surgery (with or without the need for neoadjuvant chemotherapy) with one or more injection-accessible (allowing ultrasound guidance) nodal tumors.
- Injectable tumor lesions must have a volume between 1.00 and 10 ml, only one lesion per patient will be injected
- ECOG performance status of 0 or 1
- Willing to give informed consent in writing
Key exclusion criteria (12 listed)
- Male patients
- Patients with stage III-IV breast cancer (AJCC 8th edition)
- Patients with highly vascularized tumor or important post-biopsy hematoma
- Previous chemotherapy for breast cancer or other types of cancer within the last five years
- Other malignancies other than non-melanoma skin cancer, or controlled superficial bladder cancer. In the event of prior malignancies treated surgically, the patient must be considered NED (no evidence of disease) for a minimum of 3 years prior to enrolment
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 |
|---|---|---|
| TrimixIntratumoral TriMix injection | Drug | TriMix |
| PlaceboIntratumoral placebo injection | Drug | placebo |
Primary outcome
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time frame: 2 years
Number of patients with adverse events, total number of adverse events, dose limiting toxicities
3 secondary outcomes
Tumor microenvironment changes induced by intratumoral TriMix mRNA
Time frame: 30 days
Tumor microenvironment changes induced by intratumoral TriMix mRNA
Time frame: 30 days
TriMix mRNA induced T-cell responses
Time frame: 30 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2022.
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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.
Marian Vanhoeij, MD principal investigator
Universitair Ziekenhuis Brussel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Trimix in people with Breast Cancer Female and Early-stage Breast Cancer, run by Universitair Ziekenhuis Brussel at 1 site in Belgium.
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 17 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 19 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. 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. Some participants in this study may receive a placebo. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact UZ Brussel (+32 2 477 6015, borstkliniek@uzbrussel.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 (time frame: 2 years). 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 19 May 2022.