A Phase II Trial of Atezolizumab Plus CArboplatin Plus Nab-paclitaxel as First-line Therapy in Metastatic Triple-negative PD-L1 Positive Breast Cancer Patients - the GIM25-CAPT Trial

Consorzio Oncotech15 sites in 1 country49 target enrollmentJuly 3, 2020

ConditionsMetastatic Breast Cancer Triple Negative Breast Cancer PD-L1 Gene Mutation

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Metastatic Breast Cancer
Sponsor: Consorzio Oncotech
Enrollment: 49
Locations: 15
Primary Endpoint: Overall survival
Status: Active, not recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

Primary objective:

To provide preliminary evidence on the efficacy of atezolizumab plus carboplatin plus paclitaxel as first-line therapy in metastatic triple-negative PD-L1 positive breast cancer patients as evaluated by % 2years OS.

Secondary objective:

To provide preliminary evidence on the efficacy of atezolizumab plus carboplatin plus paclitaxel as first-line therapy in metastatic triple-negative PD-L1 positive breast cancer patients in terms of % OS at 2.5 years
To provide preliminary evidence on the efficacy of atezolizumab plus carboplatin plus paclitaxel as first-line therapy in metastatic triple-negative PD-L1 positive breast cancer patients in terms of % OS at 2 years in hormonal receptor (HR) between 1% and 10%
To provide preliminary evidence on the efficacy of atezolizumab plus carboplatin plus paclitaxel as first-line therapy in metastatic triple-negative PD-L1 positive breast cancer patients in terms of post-progression survival
To assess the activity of atezolizumab plus carboplatin plus paclitaxel as first-line therapy in metastatic triple-negative PD-L1 positive breast cancer patients in terms of ORR, and time to treatment failure
To assess the safety of atezolizumab plus carboplatin plus paclitaxel as first-line therapy in metastatic triple-negative PD-L1 positive breast cancer patients

Exploratory Objectives:

Exploratory objectives will be focused on the assessment of both tumor-centered characteristics through the NGS analysis of circulating tumor DNA (ctDNA) and immune-centric features through the evaluation of a multiparametric Cancer agnostic circuLating ImmunOsignature (CLIO):

To assess the association between patients' characteristics, treatment activity, efficacy and safety and through a CLIO in metastatic triple-negative breast cancer patients receiving atezolizumab plus carboplatin plus paclitaxel as first-line therapy
To explore the association between the CLIO and treatment activity, efficacy and safety
To explore the dynamics of circulating tumor DNA (ctDNA) levels and detectable aberrations with respect to treatment activity and efficacy Concomitant timepoints will not be used for cross-validations between the two methodologies.

Detailed Description

All eligible patients will receive carboplatin Area Under the Curve (AUC) 2 dd 1,8,15 q 28 dd, paclitaxel 90 mg/m2 dd 1,8,15 q 28 dd and atezolizumab 840 mg dd 1,15 q 28 dd and they will continue this treatment until progression of disease, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, or study termination by the Sponsor. In case of interruption of one of the three drugs for unacceptable toxicity and/or medical decision, the patient may continue to receive one or more of the remaining drugs until progression per RECIST v1.1. If the investigator decides to interrupt carboplatin and paclitaxel (for toxicity and/or medical decision), atezolizumab may be continued as maintenance therapy until disease progression or unacceptable toxicity. All patients who discontinue study treatment (including due to PD) will be followed for survival approximately every 3 months for 2 years from last patient enrolled or until death, withdrawal of consent, loss to follow-up, or study termination by the Sponsor. Imaging tumor evaluation will be performed every 12 weeks.

Registry

clinicaltrials.gov

Start Date

July 3, 2020

End Date

July 3, 2024

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Consorzio Oncotech

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Signed Informed Consent Form
•Women or men aged ≥18 years
•Histologically or cytologically confirmed adenocarcinoma of the breast with metastatic disease
•Hormone receptor-negative (ER and PgR \< 10%) and HER2-negative (IHC 0,1+ or 2+ ISH not amplified) breast cancer, based on the status of the primary tumor and/or the biopsy of metastatic disease before starting first-line therapy and assessed by local laboratory.
•Patients ER and PgR \< 1% eligible to receive atezolizumab in combination with nab-paclitaxel as standard of care treatment for metastatic triple-negative breast cancer (TNBC), regardless of study participation.
•PD-L1 positive defined as expression on tumor-infiltrating immune cells ≥1% (SP142 PD-L1 immunohistochemical assay, Ventana Medical Systems), based on the status of the primary tumor and/or the biopsy of metastatic disease before starting first-line therapy and assessed by local laboratory
•Availability of a representative tumor specimen for translational research
•Eligible for first-line taxane and carboplatin chemotherapy
•No prior chemotherapy or targeted systemic therapy (including endocrine therapy) for inoperable locally advanced or metastatic TNBC. Prior radiation therapy for metastatic disease is permitted. There is no required minimum washout period for radiation therapy; however, patients should have recovered from the effects of radiation before enrollment
•Previous chemotherapy with taxanes and/or carboplatin for early breast cancer (neoadjuvant or adjuvant setting) is permitted if completed ≥12 months before study entry

Exclusion Criteria

•Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for at least 2 weeks prior to enrollment.
•Known central nervous system (CNS) disease, except for treated asymptomatic CNS metastases, provided all of the following criteria are met:
•No ongoing requirement for corticosteroids as therapy for CNS disease (anticonvulsants at a stable dose are allowed)
•No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to enrollment
•No evidence of progression or hemorrhage after completion of CNS directed therapy Note: Patients with new asymptomatic CNS metastases detected at the screening scan must receive radiation therapy and/or surgery for CNS metastases. Following treatment, these patients may then be eligible, if all other criteria above are met.
•Uncontrolled pleural effusion, pericardial effusion, or ascites (Note: patients with indwelling catheters, such as PleurX® are allowed)
•Uncontrolled tumor-related pain
•Patients requiring narcotic pain medication must be on a stable regimen at study entry.
•Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period.
•Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not presently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment.

Outcomes

Primary Outcomes

Overall survival

Time Frame: 2 years

% Overall survival

Secondary Outcomes

Overall survival(2,5 years)
Post-progression survival(up 24 months from LPFV (from tumor progression until death or is censored on the date of the last follow-up consultation up to 24 months))
Overall survival in HR(2 years)
Incidence and severity od AEs and SAEs(up to 24 months)
Objective response rate(from 12 weeks to 24 months (An objective response is defined for patients with measurable disease at baseline as either a partial response (PR) or a complete response (CR) using RECIST v1.1 up to 24 months))
Time to treatment failure(from 4 weeks to 24 months (Time to treatment failure (TTF) is defined as the time from enrollment to treatment discontinuation for any reason, including disease progression, treatment toxicity, patient preference, or death up to 24 months))