Trial Title:
Intratumoral INT230-6 Followed by Neoadjuvant Immuno-chemotherapy in Patients With Early TNBC. INVINCIBLE-4-SAKK
NCT ID:
NCT06358573
Condition:
Triple-negative Breast Cancer
TNBC - Triple-Negative Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Conditions: Keywords:
triple-negative breast cancer
TNBC
Intratumoral INT230-6
neoadjuvant immuno-chemotherapy
INT230-6
early stage
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
randomized, open-label multicenter phase 2 clinical study to determine the clinical
activity, safety and tolerability of INT230-6 in patients with early stage, operable TNBC
who undergo neoadjuvant systemic treatment.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
INT230-6
Description:
INT230-6 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.
Arm group label:
Cohort A experimental
Intervention type:
Other
Intervention name:
neoadjuvant immuno-chemotherapy
Description:
Standard of care
Arm group label:
Cohort A experimental
Arm group label:
Cohort B Standard of Care
Summary:
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.
Detailed description:
Triple-negative breast cancer (TNBC) poses significant challenges due to its
aggressiveness, high relapse rates, and increased mortality. The Keynote-522 study
revealed a 19.6% incidence of event-free survival (EFS) events in early-stage TNBC
patients over 39 months. Achieving pathological complete response (pCR) and clearing
positive lymph nodes are crucial prognostic factors.
The IMP INT230-6 is a combination of the chemotherapeutic agents cisplatin and
vinblastine, along with a molecule that facilitates their distribution in tumor tissue.
INT230-6, currently in clinical trials, has demonstrated the ability to induce up to 95%
necrosis in T2 breast cancer tumors and it has been observed to stimulate systemic immune
activation during the period between diagnosis and surgery. Moreover, promising results
have been seen in seven refractory breast cancer patients, resulting in decreased Ki67
levels and a median overall survival of 12 months.
Completed and ongoing U.S. clinical trials including 91 patient a window-of-opportunity
trial demonstrate the safety and early activity of INT230-6, both alone and with
checkpoint inhibitors like pembrolizumab and ipilimumab, particularly in resistant cases.
Based on the positive outcomes, it will be assessed within this clinical trial the safety
and early clinical activity of INT230-6 in early TNBC patients, addressing the high unmet
medical need in this challenging subtype.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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: 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 the eligibility. If multifocal or
multicentric disease TNBC needs to be confirmed for each focus.
- Measurable disease in the breast with at least one lesion with a diameter ≥2cm that
is evaluable per RECIST v1.1, visible in ultrasound and injectable.
- Male or female subject Age ≥ 18 years.
- ECOG performance status 0-1
- Adequate bone marrow function (administration of G-CSF, EPO and/or blood transfusion
within 14 days before registration is not allowed):
- neutrophil count ≥ 1.5 x 109/L
- platelet count ≥ 100 x 109/L
- hemoglobin ≥ 90 g/L
- Adequate hepatic function:
- total bilirubin ≤ 1.5 x ULN, or direct bilirubin ≤ ULN for subjects with total
bilirubin levels > 1.5 x ULN
- AST and ALT ≤ 2.5 x ULN,
- Albumin 30 ≥ g/L
- Lactate Dehydrogenase (LDH) <2.5 ULN
- Adequate renal function: estimated glomerular filtration rate (eGFR) ≥ 50
ml/min/1.73 m2 (according to CKD-EPI formula or serum creatinine ≤ 1.5x ULN.
- Adequate cardiac function: Left ventricular Ejection Fraction (LVEF) ≥ 50% as
determined by echocardiography (ECHO)
- Adequate coagulation function:
- INR ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy
- aPTT ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy
- If patient is receiving anticoagulant therapy, the treating physician must
determine that the anticoagulation can be stopped at least 24 hours prior to
injection.
- Women of childbearing potential must use highly effective contraception, are not
pregnant or lactating and agree not to become pregnant during trial treatment and
until 6 months after the last dose of INT230-6 or standard of care treatment. A
negative pregnancy test before inclusion into the trial is required for all women of
childbearing potential. (www.swissmedicinfo.ch).
- Men agree not to donate sperm or to father a child during trial treatment and until
6 months after the last dose of INT230-6 or standard of care treatment
(www.swissmedicinfo.ch).
Exclusion Criteria:
- Inflammatory Breast Cancer cT4d
- 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
- History of invasive malignancy ≤3 years prior to signing informed consent (except
treated basal cell or squamous cell skin cancer or in situ cervical cancer)
- Prior chemotherapy, targeted therapy, radiation therapy or anti-PD-L1 agent for
previous breast cancer or Ductal Carcinoma in Situ (DCIS) on the same side.
- Concurrent bilateral breast cancer
- Concomitant treatment with any other experimental drug for recent breast cancer
diagnosis in another clinical trial.
- Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA II or
IV; unstable angina pectoris, history of myocardial infarction and acute coronary
syndrome requiring stenting/bypass surgery within the last six months, serious
arrhythmias requiring medication (with exception of atrial fibrillation or
paroxysmal supraventricular tachycardia), significant QT-prolongation, uncontrolled
hypertension.
- Known history of human immunodeficiency virus (HIV) or active chronic hepatitis C or
hepatitis B virus infection or any uncontrolled active systemic infection requiring
intravenous (iv) antimicrobial treatment.
- Active autoimmune disease that required systemic treatment in past 2 years (e.g.,
with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
Replacement therapy (e.g., thyroid hormone replacement, insulin, or physiologic
corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not
considered a form of systemic treatment.
- History of (non-infectious) pneumonitis that required steroids or current
pneumonitis.
- Known history of tuberculosis.
- Known history of allogeneic organ or stem cell transplant.
- Receipt of live attenuated vaccine within 30 days prior to registration.
- Diagnosis of immunodeficiency, concomitant or prior use of immunosuppressive
medication within 7 days before registration, with the exceptions of local
(intranasal, topical and inhaled) corticosteroids, or systemic corticosteroids which
must not exceed 10 mg/day of prednisone or a dose equivalent corticosteroid, and the
premedication for chemotherapy.
- Concomitant anticoagulation with warfarin or equivalent vitamin K antagonists (e.g.
phenprocoumon), factor Xa inhibitors (e.g. rivaroxaban, apixaban), direct thrombin
inhibitors (e.g. dabigatran) or platelet inhibitors/antiplatelet agents that cannot
be stopped 24 hours before the administration of INT230-6. Aspirin (up to 300
mg/day) is allowed.
- Any concomitant drugs contraindicated for use with the trial drug according to the
Investigator Brochure (IB) and the immuno-chemotherapy treatment according to the
approved product information.
- Known hypersensitivity to trial drug or to any component of the trial drug or
immuno-chemotherapy treatment.
- Any other serious underlying medical, psychiatric, psychological, familial or
geographical condition, which in the judgment of the investigator may interfere with
the planned staging, treatment and follow-up, affect patient compliance or place the
patient at high risk from treatment-related complications.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Tumor Zentrum Aarau
Address:
City:
Aarau
Zip:
5000
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Razvan Popescu, MD
Phone:
+41 62 836 78 33
Email:
razvan.popescu@hirslanden.ch
Investigator:
Last name:
Razvan Popescu, MD
Email:
Principal Investigator
Facility:
Name:
St. Claraspital
Address:
City:
Basel
Zip:
4058
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Thomas Schmid, MD
Phone:
+41 61 685 88 65
Email:
thomas.schmid@claraspital.ch
Investigator:
Last name:
Thomas Schmid, MD
Email:
Principal Investigator
Facility:
Name:
Istituto Oncologico della Svizzera Italiana (IOSI)
Address:
City:
Bellinzona
Zip:
6500
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Lorenzo Rossi, MD
Phone:
+41 91 811 85 77
Email:
lorenzo.rossi@eoc.ch
Investigator:
Last name:
Lorenzo Rossi, MD
Email:
Principal Investigator
Facility:
Name:
Kantonsspital Graubünden
Address:
City:
Chur
Zip:
7000
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Michael Schwitter, MD
Phone:
+41 81 256 75 68
Email:
michael.schwitter@ksgr.ch
Investigator:
Last name:
Michael Schwitter, MD
Email:
Principal Investigator
Facility:
Name:
Kantonsspital Baselland
Address:
City:
Liestal
Zip:
4410
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Marcus Vetter, MD
Phone:
+41 61 925 2715
Email:
marcus.vetter@ksbl.ch
Investigator:
Last name:
Marcus Vetter, MD
Email:
Principal Investigator
Facility:
Name:
Kantonsspital St. Gallen
Address:
City:
St. Gallen
Zip:
9007
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Markus Jörger, MD
Phone:
+41 76 559 10 70
Email:
markus.joerger@kssg.ch
Investigator:
Last name:
Markus Jörger, MD
Email:
Principal Investigator
Facility:
Name:
TBZO - Tumor- & Brustzentrum Ostschweiz
Address:
City:
St. Gallen
Zip:
9016
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Markus Niemeyer, MD
Phone:
+41 71 243 02 57
Email:
markus.niemeyer@tbz-ost.ch
Investigator:
Last name:
Markus Niemeyer, MD
Email:
Principal Investigator
Facility:
Name:
Kantonsspital Winterthur
Address:
City:
Winterthur
Zip:
8401
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Ursina Zürrer, MD
Phone:
+41 52 266 25 83
Email:
ursina.zuerrer@ksw.ch
Investigator:
Last name:
Ursina Zürrer, MD
Email:
Principal Investigator
Facility:
Name:
Universitätsspital Zürich - Klinik für Gynäkologie
Address:
City:
Zürich
Zip:
8091
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Isabell Witzel, Prof
Phone:
+41 43 253 64 05
Email:
isabell.witzel@usz.ch
Investigator:
Last name:
Isabell Witzel, Prof
Email:
Principal Investigator
Start date:
October 24, 2024
Completion date:
December 2029
Lead sponsor:
Agency:
Swiss Group for Clinical Cancer Research
Agency class:
Other
Source:
Swiss Group for Clinical Cancer Research
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06358573
