BCT 1702 (CHARIOT): Patients with high-risk primary triple negative breast cancer who have had anthracycline-based chemotherapy will receive Ipilimumab and Nivolumab with weekly paclitaxel, followed by definitive surgery and further treatment with Nivolumab to evaluate the safety, feasibility and efficacy of this treatment.
- Conditions
- Primary triple negative breast cancerCancer - Breast
- Registration Number
- ACTRN12617000651381
- Lead Sponsor
- Breast Cancer Trials
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Active, not recruiting
- Sex
- All
- Target Recruitment
- 34
For inclusion in the study, participants must fulfil all of the following criteria:
1) Female or male, age >= 18 years.
2) Non-metastatic, potentially operable, unilateral triple negative breast cancer, histologically defined as:
a) ER negative: with < 1% of tumour cells positive for ER by IHC irrespective of staining intensity; AND
b) PR negative: with < 1% tumour cells positive for PR by IHC irrespective of staining intensity; AND
c) HER2 negative:
i) IHC 1+, as defined by incomplete membrane staining that is faint/barely perceptible and within > 10% of invasive tumour cells; OR
ii) IHC 0, as defined by no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within >= 10% of the invasive tumour cells; OR
iii) ISH (FISH or SISH) negative based on: Single-probe average HER2 copy number < 4.0 signals/cell, OR Dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number < 4.0 signals/cell.
3) At the time of diagnosis, have previously untreated non-metastatic (M0) TNBC fulfilling the following combined primary tumour (T) and regional lymph node (N) staging per AJCC Cancer Staging Manual, 8th Edition (2017) as assessed by the local investigator on the basis of US of the breasts, and US or clinical examination of the axilla, respectively (prior to any anthracycline-based chemotherapy):
a) Ipsilateral multifocal or multicentric primary disease is allowed and the tumour focus with the most advanced T stage should be used to assess eligibility; all tumours must be confirmed TN phenotype;
b) Participants undergoing a sentinel lymph node biopsy prior to study entry will not be eligible;
c) Residual tumour requirements (post anthracycline-based chemotherapy):
i) Node Negative: The residual primary tumour (or at least one of the primary tumours in the presence of multifocal ro multicentric disease ( must be at least 15mm prior to study treatment commencement, or
ii) Residual invasive skin disease measuring >= 10 mm, or
iii) Node positive: Residual primary tumour at least 10 mm for patients with clear remaining node positive disease (at least one persisting abnormal node).
d) Invasive disease must be detectable in the post-anthrcycline biopsy taken from the breast or lymph node.
e) An assessment of tumour response prior to study entry is required by serial US and clinical examination;
f) The tumour measurement at study entry (pre-C1) can be used and compared to measurements from the diagnostic imaging performed at diagnosis (prior to the start of anthracycline-based chemotherapy).
4) Computed tomography (CT) scan of chest/abdomen (and bone scan if clinically indicated) or PET CT at diagnosis or any time prior to study entry to exclude metastases. Those participants with equivocal finding on staging at diagnosis should have staging repeated prior to study entry. Biopsies should be performed to confirm or exclude metastatic disease if possible.
5) A FFPE tumour block or representative 15-20 sections from the diagnstic core biopsy prior to anthracycline-based chemotherapy must be available.
6) The participant must have completed 4 cycles of anthracycline-based chemotherapy (AC (or EC) x 4 (3 weekly or dose dense) at standard dosing; FEC X 4). First dose of study therapy must be planned to commence within 4 weeks of last dose of anthracycline based chemotherapy. It is recommended that patients who have received dose dense anthracycline chemotherapy wait at least 3 weeks
Any one of the following is regarded as a criterion for exclusion from the study:
1) Has evidence of metastatic breast cancer or concurrent bilateral invasive breast cancer. Staging must be performed as clinically appropriate. Biopsies should be performed to confirm or exclude metastatic disease if possible.
2) Inoperable breast cancer at completion of 4 cycles of anthracycline-based chemotherapy.
3) Patients planned to receive neoadjuvant breast radiation therapy
4) Has received prior chemotherapy (apart from pre-study anthracycline component), targeted therapy, radiation therapy, immunotherapy that target immune checkpoints, co-stimulatory or co-inhibitory pathways for T cell receptors within the past 12 months.
a) Participants who are planned to receive further chemotherapy post-surgery if residual disease is present are ineligible.
5) Is currently participating and receiving study therapy, or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study treatment.
Note: participant will be excluded if she received an investigational agent with anticancer or anti-proliferative intent within the last 12 months.
6) Has received a live vaccine within 30 days of the first dose of study treatment.
Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed, however are strongly cautioned against; intranasal influenza vaccines (e.g. FluMist(R)) are live attenuated vaccines, and are not allowed.
7) Has received an inactivated influenza vaccines within 6 weeks of study treatment commencement.
8) Participants must have recovered from the effects of any major surgery for causes unrelated to breast cancer or significant traumatic injury at least 14 days before registration.
9) Participants with previous malignancies (except non-melanoma skin cancer, melanoma in situ, and in situ cancers of the following: stomach, colon, cervix, endometrium, or breast) are excluded unless a complete remission was achieved at least 2 years prior to registration and no additional therapy is required or anticipated to be required during the study period.
10) Other active malignancy requiring concurrent intervention.
11) Participants with an active, known or suspected autoimmune disease are excluded. The following are permitted to participate:
* Participants with type I diabetes mellitus
* hypothyroidism only requiring hormone replacement
* skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or
* conditions not expected to recur in the absence of an external trigger.
12) Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomisation. Inhaled or topical steroids, and adrenal replacement steroid > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed. Patients requiring steroids as a once-off, short term anti-emetics (such as that prescribed with chemotherapy) are allowed.
13) Participants with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary tox
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The rate of pathological complete response (pCR) in the breast and axilla as defined by no histologic evidence of residual invasive cancer cells on haematoxylin and eosin (H&E) evaluation of the resected breast and lymph node specimens.[Definitive surgery.]
- Secondary Outcome Measures
Name Time Method