Atezolizumab Plus CArboplatin Plus Nab-paclitaxel

NCT05266937 | Unknown Phase 2

• 1 other identifier: GIM25-CAPT
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 15

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.

Conditions

Metastatic Breast Cancer; Triple Negative Breast Cancer; PD-L1 Gene Mutation

Outcome Measures

Primary Outcomes (1)

• Overall survival

  % Overall survival

  2 years

Secondary Outcomes (6)

• Overall survival

  2,5 years

• Overall survival in HR

  2 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)

• 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)

Other Outcomes (1)

• Exploratory outcome

  continuosly during the study up to 24 months from LPFV

Study Arms (1)

Single Arm

EXPERIMENTAL

Single-arm study with the primary objective of providing preliminary evidence on the efficacy of atezolizumab plus carboplatin plus nab-paclitaxel as first-line therapy in metastatic triple-negative PD-L1 positive breast cancer patients as evaluated by % 2years OS.

Combination Product: Atezolizumab,Paclitaxel, Carboplatin

Interventions

Atezolizumab,Paclitaxel, Carboplatin COMBINATION_PRODUCT

Atezolizumab at a fixed dose of 840 milligrams via intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle + Carboplatin area under the curve 2 via IV infusion on Days 1, 8, and 15 of each 28-day cycle + nab-Paclitaxel at a dose of 100 milligrams per square meter via IV infusion on Days 1, 8, and 15 of each 28-day cycle. In the absence of disease progression or unacceptable toxicity, study treatments will continue until the end of the study (2 years from last patient enrolled or study termination by the Sponsor).

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Previous therapy with immune checkpoint inhibitors for early breast cancer (neoadjuvant or adjuvant setting) is permitted if completed ≥12 months before study entry
• ECOG performance status of 0 or 1
• Life expectancy ≥ 12 weeks
• Measurable or evaluable disease as defined by RECIST v1.1.
• Adequate hematologic and end-organ function, defined by laboratory results obtained within 2 weeks prior to the first study treatment (Cycle 1, Day 1)

You may not qualify if:

• 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.
• Uncontrolled hypercalcemia (\>1.5 mmol/L \[\>6 mg/dL\] ionized calcium or serum calcium \[uncorrected for albumin\] \>3 mmol/L \[\>12 mg/dL\] or corrected serum calcium \>ULN) or clinically significant (symptomatic) hypercalcemia
• a) Patients who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who do not have a history of clinically significant (symptomatic) hypercalcemia are eligible.
• Malignancies other than TNBC within 5 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer)
• Pregnant or lactating women, or intending to become pregnant during the study
• Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome)

Sponsors & Collaborators

• Consorzio Oncotech: lead

Study Sites (15)

Centro di Riferimento oncologico

Aviano, Pordenone, 33081, Italy

Location

A.O. Ospedale Papa Giovanni XXIII - Oncologia

Bergamo, Italy

Location

Policlinico S. Orsola Malpighi - Oncologia Medica

Bologna, MD, Italy

Location

Azienda Ospedaliera S. Croce e Carle - Oncologia

Cuneo, Italy

Location

Arcispedaliera S. Anna di Ferrara U.O. Oncologia Clinica

Ferrara, 44121, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - Oncologia ed ematologia clinica e sperimentale

Meldola, 47014, Italy

Location

Istituto Nazionale dei Tumori - Fondazione G. Pascale U.O. Oncologia Medica Senologica

Napoli, 80131, Italy

Location

Università di Napoli Federico II - Facoltà di Medicina Dipartimento di Medicina Clinica e Chirurgia - Oncologia

Napoli, 80131, Italy

Location

Azienda Ospedaliera Universitaria di Parma - Oncologia Medica

Parma, 43126, Italy

Location

IRCCS Arcispedale Santa Maria Nuova - Oncologia Medica

Reggio Emilia, 42123, Italy

Location

Istituto Nazionale Tumori Regina Elena - Oncologia Medica 1

Roma, 00144, Italy

Location

AZIENDA OSPEDALIERA SANTA MARIA TERNI - Oncologia Medica

Terni, 05100, Italy

Location

Presidio San Lazzaro - A.O.U. San Giovanni Battista di Torino (Molinette) - Oncologia

Torino, 10126, Italy

Location

Ospedale Mauriziano Umberto I - Oncologia

Torino, 10128, Italy

Location

ULSS 8 Berica- Ospedale San Bortolo di Vicenza - Oncologia

Vicenza, 36100, Italy

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

atezolizumab; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Study Officials

• Lucia Del Mastro, MD

  San Martino Hospital, Genova

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a Phase II, multicentre, single-arm study

Study Record Dates

• First Submitted: February 10, 2020
• First Posted: March 4, 2022
• Study Start: July 3, 2020
• Primary Completion: July 3, 2024
• Study Completion: July 3, 2024
• Last Updated: February 1, 2024

Record last verified: 2024-01

Locations

IT (15)