Intratumoral TriMix Injections in Early Breast Cancer Patients (TMBA)
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|ClinicalTrials.gov Identifier: NCT03788083|
Recruitment Status : Recruiting
First Posted : December 27, 2018
Last Update Posted : March 15, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer Female Early-stage Breast Cancer||Drug: Trimix Drug: Placebo||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Sequential Assignment|
|Masking Description:||Subjects will not know whether an active or non-active substance is being injected. The choice for TriMix or placebo will take place according to the predefined schedule and can not be influenced by the patient or the investigator. Only after the comparison of the tumour tissue before (the initial biopsy where the diagnosis was made) and after (obtained at second biopsy or surgery) the intratumoral injection, it will be known whether mRNA or non-active product was used for the injection.|
|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|
|Actual Study Start Date :||November 12, 2018|
|Estimated Primary Completion Date :||September 30, 2020|
|Estimated Study Completion Date :||December 30, 2020|
|Placebo Comparator: placebo||
Intratumoral placebo injection
|Active Comparator: TriMix||
Intratumoral TriMix injection
- 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
- Tumor microenvironment changes induced by intratumoral TriMix mRNA [ Time Frame: 30 days ]Tumor microenvironment changes induced by intratumoral TriMix mRNA administration from diagnostic biopsy to day 21 (visit 5) assessed by immunohistochemistry.
- Tumor microenvironment changes induced by intratumoral TriMix mRNA [ Time Frame: 30 days ]Tumor microenvironment changes induced by intratumoral TriMix mRNA administration from diagnostic biopsy to day 21 (visit 5) assessed by nanoString gene profiling
- TriMix mRNA induced T-cell responses [ Time Frame: 30 days ]TriMix mRNA induced T-cell responses assessed by immunoassays in situ and in peripheral blood
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): NCT03788083
|Contact: UZ Brussel||+32 2 477 firstname.lastname@example.org|
|Jette, Brussel, Belgium, 1090|
|Contact: UZ Brussel +32 2 477 6015 email@example.com|
|Principal Investigator: Marian Vanhoeij, MD|
|Principal Investigator:||Marian Vanhoeij, MD||Universitair Ziekenhuis Brussel|