Revisions for A Study of the Efficacy and Safety of Atezolizumab Plus Chemotherapy for Patients With Early Relapsing Recurrent Triple-Negative Breast Cancer. | Registro Público Cubano de Ensayos Clínicos

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Revision of 19 July 2023 - 4:03pm:

A Study of the Efficacy and Safety of Atezolizumab Plus Chemotherapy for Patients With Early Relapsing Recurrent Triple-Negative Breast Cancer.

General information

Section to complete general information about the trial: scientific and public title, protocol identifiers, sponsors and Source(s) of Monetary or Material Support.

Acronym of Public Title:

IMPassion 132 (MO39193)

Scientific title:

A PHASE III, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTRE STUDY OF THE EFFICACY AND SAFETY OF ATEZOLIZUMAB PLUS CHEMOTHERAPY FOR PATIENTS WITH EARLY RELAPSING RECURRENT (INOPERABLE LOCALLY ADVANCED OR METASTATIC) TRIPLE-NEGATIVE BREAST CANCER

Acronym of Scientific Title:

IMPassion 132

Secondary indentifying numbers:

MO39193

NCT03371017

Issuing authority of the secondary identifying numbers:

Roche Servicios S.A.

ClinicalTrials.gov

Source(s) of monetary or material support:

Primary Sponsor - Roche Servicios S.A.

Authorization for beginning

Section to complete information about the regulatory approval of clinical trial: regulatory agency name, approval date and reference number in the agency.

Regulatory instance to authorize the initiation of the study:

Center for State Control of Drugs, Medical Devices and Equipment (CECMED)

Authorization date :

17/11/2017

Reference number:

00009

Principal investigator

Section to complete information about Email address, telephone number and postal address of the Principal Investigator.

First name:

Elias

Midle name:

Antonio

Last name:

Gracia Medina

Medical Specialty :

Medical Doctor, First degree specialist in oncology

Affiliation:

National Institute of Oncology and Radiobiology (INOR)

Postal address:

Calle 29 esquina. F, Vedado, Plaza de la Revolucion

City:

Havana

Country:

Cuba

Zip Code:

10400

Telephone:

+53-53309067

Email address:

eliasg@inor.sld.cu

Clinical sites to participate

Section to complete the data related to the clinical sites involved in the trial: site and responsible investigator for every site.

Countries of recruitment:

Algeria

Bosnia and Herzegovina

Brazil

Cuba

Finland

France

Germany

Humgary

Italy

Kazakhstan

Republic of Korea

Mexico

Morocco

Panama

Russian Federation

Serbia

Singapore

South Africa

Spain

Turkey

United Kingdom

United States

Clinical sites:

Havana, Hospital Hermanos Ameijeiras, Dr. Jorge Luis Soriano Garcia, Medical Doctor, First degree specialist in oncology

Research ethics committees:

Comité de Ética de Investigación del Instituto Nacional de Oncología y Radiología (INOR), in review

Comité de Ética de Investigación del Hospital Clínico Quirúrgico Hermanos Ameijeiras (CEIHHA), in review

Recruitment status

Section to complete information about the recruitment status and the date of first enrolment subject

Recruitment status:

Recruiting

Date of first enrollment:

11/01/2018

Health condition and Intervention

Section to complete information about the primary medical condition(s) or problem(s) studied and, a characteristics of the intervention(s).

Health condition(s) or Problem(s) studied:

Triple Negative Breast Neoplasms

Health condition(s) code:

Triple Negative Breast Neoplasms

Breast Neoplasms

Breast Diseases

Skin Diseases

Skin and Connective Tissue Diseases

Intervention(s):

Atezolizumab group (Experimental): Atezolizumab + Gemcitabine/Carboplatin or Capecitabine Atezolizumab will be administered, 1200 mg by Intravenous (IV) infusion with Gemcitabine 1000 mg/m2, followed by Carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by intravenous (IV) infusion on Days 1 and 8 of each 3-week treatment cycle or with Capecitabine 1000 mg/m2, twice daily orally on Days 1 to 14, followed by a 7-day rest period in each 3-week treatment cycle Placebo group (Control): Placebo + Gemcitabine/Carboplatin or Capecitabine. Placebo will be administered, 1200 mg by Intravenous (IV) infusion with Gemcitabine 1000 mg/m2, followed by Carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by intravenous (IV) infusion on Days 1 and 8 of each 3-week treatment cycle or with Capecitabine 1000 mg/m2, twice daily orally on Days 1 to 14, followed by a 7-day rest period in each 3-week treatment cycle.

Intervention code:

Antibodies, Monoclonal, Humanized

Antineoplastic Agents

Gentamicins

Carboplatin

Capecitabine

Placebos

Infusions, Intravenous

Administration, Oral

Intervention keyword:

Atezolizumab

Outcomes and Timepoint

Section to complete information about primary and secondary outcomes including. It includes the metric or method of measurement used and, the time point for every outcome.

Primary outcome(s):

Overall survival-OS (Time form randomization until death from any cause). Measurement time: 30 months post First Patient In (FPI)

Key secondary outcomes:

1. Proportion of patients alive 12 months. Measurement time: Randomization; 12 months post randomization 2. Proportion of patients alive 18 months. Measurement time: Randomization; 18 months post randomization 3. Progression-free survival-PFS (Time from randomization until to the first occurrence of disease progression or death. It will determined by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)). Measurement time: Randomization to the first occurrence of disease progression or death (through the end of study, approximately 36 months). 4. Objective response rate-ORR (Proportion of patients with an objective response, defined as a complete response (CR) or a partial response (PR), as determined by the investigator according to RECIST 1.1). Measurement time: Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until PD, withdrawal of consent, death, or study termination (approximately 36 months). 5. Duration of objective response-DoR (Time from the first occurrence of a documented objective response to disease progression or death Determined by the investigator according to RECIST 1.1). Measurement time: Through the end of study, approximately 36 months. 6. Clinical benefit rate-CBR (Proportion of patients with a complete response (CR), Partial Response (PR) or Stable Disease (SD) as determined by the investigator according to RECIST 1.1). Measurement time: 8 weeks for the first 12 months after treatment initiation and every 12 weeks thereafter until disease progression (through the end of study, approximately 36 months). 7. Time to deterioration (TTD) of the GHS / HRQoL, defined by a minimally significant decrease of ≥10 points on the GHS / HRQoL scale (points 29, 30) of the EORTC QLQ-C30 at two consecutive evaluations time points. 8. Average and average changes from the baseline point in the function (physical, emotional, social and cognitive function) and the symptoms related to the disease / treatment per treatment cycle, as assessed by the functional scales and all the items / symptoms scales of the EORTC QLQ-C30 and the QLQ-BR23. 9. Proportion of patients reporting each response option at each point of the evaluation time of item GP5 of the FACT-G. 10. Scores of the health services of the EQ-5D-5L questionnaire. 11. Incidence, nature and severity of adverse events (AEs), severity determined in accordance with version 4.0 of the Common Terminology Criteria for Adverse Events of the National Cancer Institute (NCI CTCAE v4.0). 12. Change from baseline in vital signs and objective physical findings. 13. Change with respect to the baseline in the results of the objective clinical laboratory tests. 14. Peak and minimum value of serum atezolizumab concentrations (Cmax and Cmin.) At specific time points during treatment. 15. Incidence of anti- drug antibodies (ADA) during the study compared to the prevalence of ADA at baseline. 16. Relationship between the state of ADA and the points of measurement of effectiveness, safety or PK. 17. Relationship between the expression of PD-L1 protein by immunohistochemistry (SP142 Ventana® assay) in the tumor tissue obtained in the selection and clinical outcomes (predefined analysis according to the stratification groups of PD-L1, that is, CI0 compared to CI1 / 2/3). 18. Relationship between tumor biomarkers related to the immune system or related to the type of disease (including but not limited to TIL and the CD8 differentiation group) by immunohistochemistry in tumor tissues and clinical outcomes. 19. Relationship between PD-L1 status measured by different immunohistochemical assays and clinical outcomes. 20. Relationship between some molecular subgroups and characteristic patterns of predefined genes through the analysis of ribonucleic acid (RNA) expression in tumor tissues and clinical outcomes. 21. Relationship between deoxyribonucleic acid (DNA) mutations, the mutation load evaluated in tumor tissues and clinical outcomes. 22. Relationship between exploratory biomarkers (including but not limited to DNA, proteins and circulating free cytokines) in plasma taken before treatment, during treatment and in the progression of the disease, and clinical outcomes. 23. Changes in blood and tissue biomarkers under treatment with chemotherapy +/- atezolizumab in relation to the clinical outcome. 24. Correlation of the findings of immune biomarkers in blood and tissue samples from this study with the findings of other studies in TNMC and other types of tumors.

Selection criterias

Section to complete information about the inclusion and exclusion criteria for participant selection, including age and gender.

Gender:

Male/Female

Minimum age:

18 years old

Maximum age:

None

Inclusion criteria:

1. Histologically confirmed triple negative breast cancer(TNBC) that is either locally recurrent, inoperable and cannot be treated with curative intent or is metastatic 2. Documented disease progression occurring within 12 months from the last treatment with curative intent 3. Have not received prior chemotherapy or targeted systemic therapy for their locally advanced inoperable or metastatic recurrence. 4. Prior radiation therapy for recurrent disease is permitted 4. Measurable or non-measurable disease, as defined by RECIST 1.1 5. Availability of a representative formalin-fixed paraffin-embedded (FFPE) tumour block (preferred) or at least 25 unstained slides with an associated pathology report, if available 6. Eastern Cooperative Oncology Group performance status 0-1 7. Life expectancy ≥ 12 weeks 8. Adequate haematologic and end-organ function 9. Negative human immunodeficiency virus (HIV) test ---Negative hepatitis B surface antigen (HBsAg) test at screening 10. Negative total hepatitis B core antibody (HBcAb) test at screening, or positive HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening. The HBV DNA test will be performed only for patients who have a positive HBcAb test 11. Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening. 12. Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of ≤1% per year during the treatment period and for at least 5 months after the last dose of study treatment 13. Men must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm

Exclusion criteria:

1. 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 > 2 weeks prior to randomisation 2. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases. 3. Symptomatic or rapid visceral progression 4. No prior treatment with an anthracycline and taxane 5. History of leptomeningeal disease 6. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) (patients with indwelling catheters such as PleurX® are allowed) 7. Uncontrolled tumour-related pain 8. Uncontrolled or symptomatic hypercalcemia 9. Malignancies other than TNBC within 5 years prior to randomisation) 10. Significant cardiovascular disease, within 3 months prior to randomisation, unstable arrhythmias, or unstable angina 11. Presence of an abnormal ECG 12. Severe infection requiring oral or IV antibiotics within 4 weeks prior to randomisation, including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia. 13. Current treatment with anti-viral therapy for HBV. 14. Major surgical procedure within 4 weeks prior to randomisation or anticipation of the need for a major surgical procedure during the course of the study other than for diagnosis 15. Treatment with investigational therapy within 28 days prior to randomisation 16. Pregnant or lactating, or intending to become pregnant during or within 5 months after the last dose of study treatment Related to Atezolizumab: 17. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanised antibodies or fusion proteins 18. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or to any component of the atezolizumab formulation 19. History of autoimmune disease 20. Prior allogeneic stem cell or solid organ transplantation 21. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computerised tomography (CT) scan History of radiation pneumonitis in the radiation field (fibrosis) is permitted. 22. Active tuberculosis 23. Receipt of a live, attenuated vaccine within 4 weeks prior to randomisation or anticipation that a live, attenuated vaccine will be required during atezolizumab/placebo treatment or within 5 months after the last dose of atezolizumab/placebo 24. Prior treatment with CD137 agonists, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway targeting agents 25. Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL]-2) within 4 weeks or five half-lives of the drug (whichever is longer) prior to randomisation 26. Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to randomisation, or anticipated requirement for systemic immunosuppressive medications during the trial Related to Capecitabine: 27. Inability to swallow pills 28. Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, or ulcerative colitis 29. Known dihydropyrimidine dehydrogenase (DPD) deficiency or history of severe and unexpected reactions to fluoropyrimidine therapy in patients selected to receive capecitabine Related to Carboplatin/Gemcitabine: 30. Hypersensitivity to platinum containing compounds or any component of carboplatin or gemcitabine drug formulations in patients selected to receive carboplatin and Gemcitabine.

Type of population:

Adults

Type of participant:

Patients

Study design

Section to complete information about the characteristics of the study design.

Type study:

Interventional

Purpose:

Treatment

Allocation:

Randomized controlled trial

Masking:

Double Blind

Control group:

Placebo

Study design:

Parallel

Phase:

3

Target sample size:

350 global, 6 in Cuba

Contact for public queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to general queries, including information about current recruitment status

First Name:

María Fernanda

Last Name:

Manavella

Specialty:

Nutrition

Affiliation:

F. Hoffmann-La Roche Ltd

Postal Address:

Ultrapark Free Zone, Building 4.

City:

La Aurora de Heredia.

Country:

Costa Rica

Zip Code:

3438-1000

Telephone:

+506 2298-0000

Email :

maria_fernanda.manavella@roche.com

Contact for scientific queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to scientific queries.

First Name:

María Fernanda

Last Name:

Manavella

Specialty:

Nutritionist

Affiliation:

F. Hoffmann-La Roche Ltd

Postal Address:

Ultrapark, Building 4, La Aurora de Heredia, Costa Rica

City:

Heredia

Country:

Costa Rica

Zip Code:

3438-1000

Telephone:

+506 2298-0000

Email :

maria_fernanda.manavella@roche.com

About study completion

Section to complete the data related to the study completion.

Final enrolment number:

3 in Cuba

Study completion date:

30/06/2022

Date of available results:

25/05/2023

Date of first publication:

25/12/2023

Registration and Update

Section to complete information about the name of Primary Registry, date of registration and the unique ID number assigned by the registry (RPCEC).

Primary registry:

RPCEC

Unique ID number:

RPCEC00000280

Date of Registration in Primary Registry:

10/07/2018

Record Verification Date:

2021/08/18

Next update date:

2022/08/18

Link to the spanish version:

Click here

Registered Trials

Registration process

A Study of the Efficacy and Safety of Atezolizumab Plus Chemotherapy for Patients With Early Relapsing Recurrent Triple-Negative Breast Cancer.

About the RPCEC

Useful resources