Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202201721209443 Date of Approval: 24/01/2022
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title The purpose of this study is to compare the effects, good or bad, of atezolizumab plus trastuzumab emtansine versus placebo plus trastuzumab emtansine in patients with HER2-positive early breast cancer.
Official scientific title A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED CLINICAL TRIAL TO EVALUATE THE EFFICACY AND SAFETY OF ADJUVANT ATEZOLIZUMAB OR PLACEBO AND TRASTUZUMAB EMTANSINE FOR HER2-POSITIVE BREAST CANCER AT HIGH RISK OF RECURRENCE FOLLOWING PREOPERATIVE THERAPY
Brief summary describing the background and objectives of the trial In this study, the trial subjects will get either atezolizumab plus trastuzumab emtansine or placebo plus trastuzumab emtansine. A placebo looks like a drug but has no active ingredient. Atezolizumab is a cancer immunotherapy and binds to a protein called PD-L1, blocking the usual function of PD-L1, in order to help your immune system to recognize and fight off cancer cells. Atezolizumab (Tecentriq→) is approved for the treatment of urothelial carcinoma (a type of bladder cancer), some lung cancers, hepatocellular carcinoma (a type of liver cancer), melanoma (a type of skin cancer), as well as triple-negative breast cancer (which is a breast cancer that is different from the breast cancer you have). However, in this study, atezolizumab is an experimental drug, which means that health authorities have not approved atezolizumab either alone or in combination with trastuzumab emtansine for the treatment of HER2-positive breast cancer. Trastuzumab emtansine is a drug that combines trastuzumab (Herceptin→), a drug that attaches to HER2 proteins on the surface of cancer cells, and a chemotherapy drug. Combining these drugs means that the chemotherapy drug is delivered specifically to cancer cells with HER2 on their surface and destroys them. Trastuzumab emtansine (Kadcyla®) has been approved for the treatment of HER2-positive breast cancer. However, trastuzumab emtansine is not approved in combination with atezolizumab which is the combination tested in this clinical trial. This study will evaluate the efficacy, safety, and pharmacokinetics of adjuvant atezolizumab when given in combination with trastuzumab emtansine compared with placebo and trastuzumab emtansine for patients with residual invasive HER2-positive breast cancer following neoadjuvant taxane-based and HER2-targeted therapy including trastuzumab, who are at high risk of disease recurrence.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) ASTEFANIA
Disease(s) or condition(s) being studied Cancer
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/03/2022
Actual trial start date
Anticipated date of last follow up 31/10/2034
Actual Last follow-up date
Anticipated target sample size (number of participants) 1700
Actual target sample size (number of participants)
Recruitment status Active, not recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Central randomisation by phone/fax Masking/blinding used Care giver/Provider,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group placebo plus trastuzumab emtansine Atezolizumab placebo 1200 mg IV Q3W and trastuzumab emtansine 3.6 mg/kg IV Q3W for 14 cycles 14 cycles One infusion of Atezolizumab placebo 1200 mg IV Q3W and trastuzumab emtansine 3.6 mg/kg IV Q3W 850 Placebo
Experimental Group Atezolizumab plus trastuzumab emtansine Atezolizumab 1200 mg IV Q3W and trastuzumab emtansine 3.6 mg/kg IV Q3W for 14 cycles 14 cycles Atezolizumab 1200 mg IV Q3W and trastuzumab emtansine 3.6 mg/kg IV Q3W 850
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
-Histologically confirmed invasive breast carcinoma -Centrally-confirmed human epidermal growth factor receptor 2 (HER2)-positive invasive breast cancer -Centrally confirmed PD-L1 and hormone receptor status -Clinical stage at disease presentation: cT4/anyN/M0, any cT/N2-3/M0, or cT1-3/N0-1/M0 (participants with cT1mi/T1a/T1b/N0 are not eligible) -Completion of pre-operative systemic chemotherapy including at least 9 weeks of taxane and 9 weeks of trastuzumab (anthracycline and/or additional HER2-targeted agents are permitted) <=12 weeks between primary surgery and randomization -Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 -Screening left ventricular ejection fraction (LVEF) >= 50% and no decrease in LVEF by >15% from the pre-chemotherapy LVEF. If no pre-chemotherapy LVEF, screening LVEF >= 55% -Life expectancy >= 6 months -Adequate hematologic and end organ function -Stage IV breast cancer -An overall response of disease progression according to the investigator at the conclusion of preoperative systemic therapy -Prior treatment with T-DM1, or atezolizumab, or other immune checkpoint inhibitors -History of exposure to various cumulative doses of anthracyclines -History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or ductal carcinoma in situ (DCIS) -Current grade >=2 peripheral neuropathy -History of idiopathic pulmonary fibrosis, organizing pneumonia, or pneumonitis -History of or active autoimmune disease or immune deficiency -Treatment with immunostimulatory or immunosuppressive agents -Cardiopulmonary dysfunction -Any known active liver disease 80 and over: 80+ Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 100 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 19/11/2021 The Aga Khan University Hospital
Ethics Committee Address
Street address City Postal code Country
3rd Parklands Avenue, Off Limuru Road P.O. Box 30270, Nairobi 00100 Nairobi 00100 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Invasive Disease-free Survival (IDFS) IDFS event is defined as the time from randomization to the first occurrence of the following events: ipsilateral invasive breast tumor recurrence, ipsilateral local-regional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, death from any cause. From randomization up to approximately 6 years
Secondary Outcome IDFS Including Second Primary Non-breast Invasive Cancer [ Time Frame: From baseline up to 10 years ] Disease-free Survival (DFS) [ Time Frame: From baseline up to 10 years ] Overall Survival (OS) [ Time Frame: From baseline up to 10 years ] Distant Recurrence-free Interval (DRFI) [ Time Frame: From baseline up to 10 years ] Number of Participants with Clinically Meaningful Deterioration in Global Health Status/Quality of Life (GHS/QoL) Physical, Role, and Cognitive Function [ Time Frame: From baseline until 2 years after study treatment completion/discontinuation visit (approximately 3 years) ] Clinically Meaningful Deterioration will be Measured by Scales of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer (EORTC QLQ C30) Mean Absolute Scores in GHS/QoL, Physical, Role, and Cognitive Function, as Assessed Using the EORTC QLQ-C30 [ Time Frame: From baseline until 2 years after study treatment completion/discontinuation visit (approximately 3 years) ] The European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30) is a self-reported measure. Functioning and symptoms items are scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. GHS and QoL items are scored on a 7-point scale: 1=Very poor, 2, 3, 4, 5, 6, 7=Excellent. Scores will be transformed to a range of 0 to 100, with higher scores (i.e. closer to 100) reflecting better functioning, better GHS/QoL, and worse symptoms. Respective timepoints have been listed above
Secondary Outcome Mean Change From Baseline Scores in GHS/QoL, Physical, Role, and Cognitive Function, as Assessed Using the EORTC QLQ-C30 [ Time Frame: From baseline until 2 years after study treatment completion/discontinuation visit (approximately 3 years) ] The European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30) is a self-reported measure. Functioning and symptoms items are scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. GHS and QoL items are scored on a 7-point scale: 1=Very poor, 2, 3, 4, 5, 6, 7=Excellent. Scores will be transformed to a range of 0 to 100, with higher scores (i.e. closer to 100) reflecting better functioning, better GHS/QoL, and worse symptoms. Percentage of Participants with Adverse Events (AEs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) [ Time Frame: From baseline up to 10 years ] Maximum Serum Concentrations (Cmax) for Atezolizumab [ Time Frame: Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, Day 1 of Cycles 2, 3 and 8 pre-infusion (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1) ] Cmax for Trastuzumab Emtansine [ Time Frame: Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1) ] Respective timepoints have been listed above
Secondary Outcome Cmax for Total Trastuzumab [ Time Frame: Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1) ] Cmax for DM1 [ Time Frame: Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1) ] DM1 = a thiol-containing maytansinoid anti-microtubule agent; N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)-maytansine Minimum Serum Concentrations (Cmin) for Atezolizumab [ Time Frame: Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, Day 1 of Cycles 2, 3 and 8 (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1) ] Percentage of Participants with Anti-drug Antibodies (ADAs) to Atezolizumab [ Time Frame: Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, Day 1 of Cycles 2, 3 and 8 (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1) ] Percentage of Participants with ADAs to Trastuzumab Emtansine [ Time Frame: Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1) ] Respective timepoints have been listed above.
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Aga Khan University Hospital Nairobi 3rd Parklands Avenue, Off Limuru Road Nairobi 00100 Kenya
International Cancer Institute Nandi Road 8/10, Eldoret, Kenya, 8088-30100 Eldoret 30100 Kenya
Uganda Cancer Institute P.O.BOX 3935, Kampala, Uganda Upper Mulago Hill Road Kampala Uganda
FUNDING SOURCES
Name of source Street address City Postal code Country
Hoffmann La Roche The Atrium, 6th Floor Chaka Road, off Lenana Road P.O. Box 44212-00100 Nairobi, Kenya Nairobi 00100 Switzerland
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Hoffmann La Roche The Atrium, 6th Floor Chaka Road, off Lenana Road P.O. Box 44212-00100 Nairobi, Kenya Nairobi 00100 Switzerland Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Saleh Mansoor mansoor.saleh@aku.edu +254709931500 Aga Khan University, Nairobi, 3rd Parklands Avenue, Nairobi-Kenya
City Postal code Country Position/Affiliation
Nairobi 00100 Kenya Professor of Hematology and Oncology
Role Name Email Phone Street address
Public Enquiries Eileen Koske eileen.koske@roche.com +254721375237 The Atrium, 6th Floor Chaka Road, off Lenana Road P.O. Box 44212-00100 Nairobi, Kenya
City Postal code Country Position/Affiliation
Nairobi Kenya Country Study and SSU Manager East Africa
Role Name Email Phone Street address
Scientific Enquiries Beatrice Nyawira beatrice.nyawira@roche.com +41795039138 F Hoffmann-La Roche Ltd, Bldg. 1 Grenzacherstrasse 124-CH 4070 Basel, Switzerland
City Postal code Country Position/Affiliation
Basel Switzerland Switzerland Medical Director HER2 Breast Cancer Portfolio
Role Name Email Phone Street address
Principal Investigator Fredrick Asirwa director@intercancer.com +254700522149 International Cancer Institute, Nandi Road 8/10, Eldoret, Kenya, 8088-30100
City Postal code Country Position/Affiliation
Eldoret 30100 Kenya Professor of Hematology and Oncology
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes There is a plan to share IPD. Plan description: -Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). -Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). --For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).There are no publications yet Clinical Study Report Roche commits to submit a manuscript to a peer-reviewed journal reporting primary clinical trials results no later than 18 months after the first product approval or decision to discontinue development of the product. Available studies are listed and available on the Vivli platform. Data requestors should use the Vivli data request form to request companies data Package(s). If approved requestors will need to sign a Data Use Agreement and the anonymized data will be shared in the Vivli secure research environment.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://vivli.org/ourmember/roche/ No
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Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
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