Intratumoral INT230-6 Followed by Neoadjuvant Immuno-chemotherapy in Patients With Early TNBC. INVINCIBLE-4-SAKK
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorSwiss Cancer Institute
About this trial
About 10-20% of all individuals with breast cancer have a so-called triple-negative tumor (TNBC). This type of breast cancer has a particularly unfavorable course and a higher mortality rate compared to other forms of breast cancer. Research studies show that it is important for individuals with TNBC to achieve a so-called pathologic complete response (pCR) to treatment. In the phase II study SAKK 66/22, it is being investigated whether the administration of the drug INT230-6 before surgery for breast cancer can increase the rate of pCR in the tumor and affected lymph nodes. The tolerability of INT230-6 as well as other factors such as response to treatment and the possibility of breast-conserving surgery are also being examined.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Written informed consent according to country specific law and ICH GCP E6(R2) regulations before registration and prior to any trial specific procedures.
Newly histologically diagnosed, previously untreated locally advanced non-metastatic TNBC as defined by the most recent American Society of Clinical Oncology (ASCO) / College of American Pathologist (CAP) guidelines .
The following stages according to staging per American Joint Committee on Cancer (AJCC) for breast cancer staging criteria version 8 are included: cT1c (1.5-2cm) N1-3 M0 or cT2-4c N0-3 M0.
Multifocal and multicentric primary tumors are allowed and the tumor with the most advanced T stage should be used to assess eligibility. If multifocal or multicentric disease TNBC needs to be confirmed for each focus.
Disqualifiers
Inflammatory Breast Cancer cT4d
Unfavorable relation between tumor size and breast size as determined by judgement of the treating physician, surgeon and/or investigator, where tumor shrinkage during neoadjuvant immunochemotherapy is required for breast conserving surgery to be considered.
Unfavorable tumor location that can potentially result in an unfavorable cosmetic outcome (e.g. high upper inner quadrant) and/or close skin contact by judgment of the treating physician, surgeon and/or investigator.
The following histological subtypes of TNBC are excluded: Classic adenoid cystic carcinoma, secretory carcinoma, low-grade adenosquamous carcinoma, tall cell carcinoma with reversed polarity, high-grade metaplastic
Trial design
Design model
Parallel
Treatments tested in this trial
INT230-6
DrugINT230-6 is a formulation consisting of an proprietary amphiphilic cell penetration enhancer molecule, 8-((2-hydroxybenzoyl)amino)octanoate, also referred to as SHAO, combined with cisplatin and vinblastine sulfate. The IMP is without marketing authorization in Switzerland and anywhere in the world.
neoadjuvant immuno-chemotherapy
Other interventionStandard of care
Treatment groups
61 Participants
are divided into 2 treatment groupsGroup A: Cohort A experimentalExperimental treatment 2 interventions
Group B: Cohort B Standard of CareOther 1 intervention
Trial outcomes
Primary outcomes
1
Pathological complete response (pCR) in the primary tumor (ypT0/Tis) and affected lymph nodes (ypN0).
The two following criteria need to be fulfilled for pCR: No invasive breast cancer in primary tumor (noninvasive breast residuals allowed) ypT0/Tis No invasive breast cancer in affected lymph nodes ypN0 The primary endpoint will be analyzed based on the resected patients set. The endpoint is evaluated according to the assessment of the local pathologist.
Time frame
At the date of tumor assessment after surgery, estimated at 29 to 32 weeks after treatment start for cohort A and at 27 to 30 weeks after treatment start for cohort B.Secondary outcomes
1
pCR (invasive and in-situ, only invasive, respectively) in the breast
No invasive and no in situ breast cancer in primary tumor ypT0 No invasive breast cancer in affected lymph nodes ypN0 The endpoint will be analyzed based on the resected patients set. The endpoint is evaluated according to the assessment of the local pathologist.
Time frame
At the date of tumor assessment after surgery, estimated at 29 to 32 weeks after treatment start for cohort A and at 27 to 30 weeks after treatment start for cohort B.2
pCR in lymph nodes
No invasive and no in situ breast cancer in primary tumor ypT0 No invasive breast cancer in affected lymph nodes ypN0 The endpoint will be analyzed based on the resected patients set. The endpoint is evaluated according to the assessment of the local pathologist.
Time frame
At the date of tumor assessment after surgery, estimated at 29 to 32 weeks after treatment start for cohort A and at 27 to 30 weeks after treatment start for cohort B.3
Pattern of non pCR
Pattern in the remaining tumor is for example visible circle or tumor border, moon shaped residual tumor, islands of tumor in sea of necrosis, tumor streaks radiating from the main tumor into the surrounding tissue, single tumor cells (e.g. in lobulary tumor). This endpoint will be analyzed based on the subset of patients in the resected patients set who did not achieve pCR in the primary tumor (any invasive cancer in primary tumor).
Time frame
At the date of tumor assessment after surgery, estimated at 29 to 32 weeks after treatment start for cohort A and at 27 to 30 weeks after treatment start for cohort B.4
Overall response according to RECIST v1.1
Overall response (OR) is defined as complete response (CR) or partial response (PR) in the last pre-surgery tumor assessment compared with baseline MRI evaluated according to RECIST v1.1. In the subset of patients in cohort A additionally the change from baseline to the MRI between the 2nd injection and start of immunochemotherapy will be evaluated. The Criteria for RECIST v1.1. will be used with one modification: the injected lesion will still be measured/evaluated for this endpoint. Rationale: For a large proportion of the patients the injected lesion will be the only tumor lesion (cT2-4, cN0) or it will contain the majority of the tumor burden (in cN1 cases). Therefore, not evaluating this lesion would result in to many patients lost for this endpoint. This endpoint will be analyzed based on the FAS (Full Analysis Set).
Time frame
At 1 to 4 weeks after last SOC treatment and before surgery, estimated at 27 to 30 weeks after treatment start for cohort A and at 25 to 28 weeks after treatment start for cohort B.Sponsors and contacts
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Source ClinicalTrials.gov