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New treatment option for Triple Negative Breast Cancer Metastatic
Official title Restoring Sensitivity To Immunotherapy In Advanced Triple Negative Breast Cancer Exploiting Ceralasertib Priming Followed By Combined Durvalumab/Nab-Paclitaxel
ClinicalTrials.gov ID: NCT05582538
What this study is testing
What is Ceralasertib?
Ceralasertib is an investigational medicine, given as a pill taken by mouth, being studied as a potential treatment for triple negative breast cancer metastatic.
Also referred to as AZD6738.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This study will evaluate the efficacy and safety of ceralasertib followed by durvalumab plus nab-paclitaxel in 37 patients with TNBC, whose tumor relapsed following treatment with curative intent for early disease, which must have included immunotherapy and chemotherapy as part of the radical locoregional therapy (either adjuvant, neoadjuvant or both).
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- ATRiBRAVE trial written informed consent, prior to any study specific procedures
- Age ≥18 years old
- Ability to comply with the study protocol in the investigator's judgment.
- Ability to swallow and retain oral medication
- Availability of a formalin-fixed, paraffin-embedded block (FFPE) containing primary tumor tissue or at least 10-20 unstained tumor slides
You likely can't join if
- Diagnosis of ataxia telangiectasia.
- Any previous treatment with ATR inhibitors, DNA-damage repair inhibitors.
- Patients, who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4 therapy:
- Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
- All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study.
- Must not have experienced a ≥ Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior...
See the full eligibility criteria
Who can join
- ATRiBRAVE trial written informed consent, prior to any study specific procedures
- Age ≥18 years old
- Ability to comply with the study protocol in the investigator's judgment.
- Ability to swallow and retain oral medication
- Availability of a formalin-fixed, paraffin-embedded block (FFPE) containing primary tumor tissue or at least 10-20 unstained tumor slides
- Metastatic TNBC patients who have not received prior systemic cytotoxic therapy in the advanced setting and whose tumor have relapsed from treatment with curative intent for early disease, which must have included ICI...
- Documented disease progression (e.g., with biopsy sample, pathology or imaging report) since the last treatment in the early setting with curative intent (neo/adjuvant regimen)
- Negative ER/PgR (defined as \<10% of tumor cells expressing ER and PgR hormonal receptors) and HER2 status (HER2 IHC score 0, 1+ or 2+ non-amplified by in situ hybridization) must be confirmed in the most recent tumor...
- Evaluable disease, as defined by RECIST 1.1
- ECOG performance status 0-1 (refer to Appendix 1)
- Patients must have a life expectancy ≥ 3 months from proposed first dose date.
- Patients must have acceptable bone marrow, liver and renal functions measured within 28 days prior to administration of study treatment
- Body weight \> 30kg
- Women with childbearing potential should complete a pregnancy test with negative result within 28 days of study treatment and be willing to use effective contraceptive methods from screening to 90 days after the last...
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm from screening to 90 days after the last dose of durvalumab.
What rules you out
- Diagnosis of ataxia telangiectasia.
- Any previous treatment with ATR inhibitors, DNA-damage repair inhibitors.
- Patients, who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4 therapy:
- Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
- All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study.
- Must not have experienced a ≥ Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE: Patients with endocrine AE of ≤ Grade 2 are permitted to...
- Must not have required the use of additional immunosuppression other than corticosteroids infliximab or Cellcept for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently...
- Treatment with any investigational product during the last 28 days before the enrollment.
- Patients must have had a washout period of 3 weeks for any prior cancer therapy prior to the start of study drug. The following intervals between the end of the prior treatment and first dose of study drug must be...
- Current or prior use of immunosuppressive medication within 4 weeks prior to the first dose of durvalumab, with the exceptions of intranasal, topical, inhaled corticosteroids, and systemic corticosteroids ≤ 10 mg...
- Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, or other solid tumours curatively treated with no evidence of disease for ≤3 years.
- Any gastrointestinal condition that would preclude adequate absorption of ceralasertib, including but not limited to inability to swallow oral medication, refractory nausea and vomiting, chronic gastrointestinal...
- Active or prior documented autoimmune or inflammatory disorders (including IBD [e.g. Crohn's disease, ulcerative colitis or diverticulitis], SLE, sarcoidosis syndrome, tuberculosis, Wegener syndrome, myasthenia gravis...
- Known active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc), at screening. Participants with a past or resolved HBV...
- Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and...
- Receipt of a live, attenuated vaccine within 30 days prior to the first dose of study treatment.
- Patients with confirmed COVID-19 infection by PCR test who have not made a full recovery
- History of allogeneic organ transplantation.
- Untreated central nervous system (CNS) metastatic disease or cord compression. Note: Patients with asymptomatic central nervous system (CNS) metastases are eligible, provided that all of the following criteria are met...
- History of leptomeningeal disease
- Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia or vitiligo
- Resting ECG with measurable QTcF \> 470 msec on 2 or more time points within a 24-hour period or family history of long QT syndrome.
- Patients with cardiac problem as follows: uncontrolled hypertension or hypotension (BP ≥150/95 mmHg despite medical therapy, BP \ 20 mmHg), Left ventricular ejection fraction \ 100 bpm on ECG at rest or any clinically...
- Stroke or transient ischemic attack in the last 6 months prior to screening.
- Uncontrolled symptomatic pleural effusion, pericardial effusion, or ascites.
- Uncontrolled hypercalcemia (\> 1.5 mmol/L ionized calcium or calcium \> 12 mg/dL or corrected serum calcium \> ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy.
- Severe infection within 4 weeks prior to the first dose of study treatment (Cycle 1, Day 1), including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
- Treatment with oral or IV antibiotics within 2 weeks prior to initiation of study treatment (Cycle 1, Day 1).
- Patients receiving routine antibiotic prophylaxis (e.g., to prevent chronic obstructive pulmonary disease exacerbation, urinary tract infection or for dental extraction) are eligible.
- As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases that places the patient at unacceptable risk of toxicity or non-compliance. Examples include, but are not limited to, diabetes type...
- Concomitant use of known potent cytochrome P (CYP) 3A inhibitors (e.g., ketoconazole,itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir...
- Concomitant use of known strong CYP3A inducers (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort). The required washout period prior to...
- Receiving or having received, concomitant medications, herbal supplements, and/or foods that significantly modulate Pgp activity (washout periods of 5 half-lives).
- Known hypersensitivity to ceralasertib, durvalumab or nab-paclitaxel or any of their excipients
The study team makes the final eligibility decision.
Where it's taking place
- Novara, Novara, Italy
- Bergamo, Italy
- Milan, Italy
- Naples, Italy
- Padova, Italy
- Reggio Emilia, Italy
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Novara, Novara, Italy; Bergamo, Italy; Milan, Italy; Naples, Italy; Padova, Italy; Reggio Emilia, Italy. Enter your location above to see the nearest site and check your eligibility.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.