Study to determine effectiveness of T-DXd (on its own or with another medication) in treating patients with HER2-positive metastatic breast cancer who have not received treatment for metastatic breast cancer
- Conditions
- Health Condition 1: C509- Malignant neoplasm of breast of unspecified site
- Registration Number
- CTRI/2021/05/033819
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- Not specified
- Target Recruitment
- 0
Age
1.Participant must be = 18 years at the time of screening (= 20 years for participants enrolled in Japan).
Type of Participant and Disease Characteristics
2.Pathologically documented breast cancer that:
(a)Is advanced or metastatic (participants who can be treated with curative intent are not eligible)
(b)Is locally assessed HER2-positive (IHC 3+ or ISH+) according to the American Society of Clinical Oncology – College of American Pathologists (ASCO-CAP) guidelines based on a tumour sample obtained in the metastatic setting.
(c)Is prospectively centrally confirmed as HER2-positive based on a tumour sample obtained in metastatic setting
(d)Is documented by local testing as HR-positive (either estrogen receptor [ER] and/or progesterone receptor [PgR] positive [ER or PgR =1%]) or HR-negative per ASCO CAP guidelines in the metastatic setting.
(e)Is centrally prospectively assessed for PIK3CA mutation status based on a tumour sample preferably obtained in the metastatic setting
7Must have an adequate tumour tissue sample available for assessment of HER2 and PIK3CA status by central laboratory (based on most recent available tumour tissue sample). An adequate sample of tumour tissue from the metastatic setting must be provided from either a newly-acquired biopsy from a region that has not been previously irradiated or the most recent archival sample. Specimens with limited tumour content and fine needle aspirates for defining tumour HER2 and PIK3CA status are not allowed. Additional details on sample requirement will be provided in the laboratory manual
8No prior chemotherapy or HER2-targeted therapy for advanced or mBC (1 prior line of endocrine therapy is allowed for mBC). Participants who have received chemotherapy or HER2-targeted therapy in the neoadjuvant or adjuvant setting are eligible, with a DFI from completion of systemic chemotherapy or HER2-targeted therapy to advanced or metastatic diagnosis of > 6 months ( > 183 days).
9Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
10At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as = 10 mm in the longest diameter (except lymph nodes, which must have short axis = 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and is suitable for accurate repeated measurements.
11Adequate organ and bone marrow function within 14 days before randomisation as follows:
Adequate bone marrow function
- = 100000/mm3. (Platelet transfusion is not allowed within 1 week prior to screening assessment)
Haemoglobin - = 9.0 g/dL NOTE: Participants requiring ongoing transfusions or growth factor support to maintain haemoglobin = 9.0 g/dL are not eligible. (Red blood cell transfusion is not allowed within 1 week prior to screening assessment)
Absolute neutrophil count= 1500/mm3. (Granulocyte-colony stimulating factor administration is not allowed within 1 week prior to screening assessment)
Adequate hepatic function
Alanine aminotransferase and aspartate aminotransferase - = 3 × ULN ( < 5 × ULN in participants with liver metastases)
Total bilirubin - = 1.5 × ULN if no liver metastases or < 3 × ULN in the presence of documented Gilbert s syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline
Serum albumin - = 2.5 g/dL
Adequate renal function <br
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1.Ineligible for any of the agents on the study. Participants with contraindications to pertuzumab, taxanes, or trastuzumab per local prescribing information or to T-DXd per the T-DXd IB cannot be enrolled to the study.
2.Has substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the subjects participation in the clinical study or evaluation of the clinical study results.
3.History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study treatment and of low potential risk for recurrence. Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that has undergone potentially curative therapy, adequately resected non-melanoma skin cancer, curatively treated in situ disease, other solid tumours curatively treated.
4.Persistent toxicities caused by previous anti-cancer therapy (excluding alopecia), not yet resolved to grade < 1 or baseline. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study treatment may be included (eg, hearing loss) after consultation with the AstraZeneca Study Physician. Participants with chronic Grade 2 toxicities may be eligible per the discretion of the investigator after consultation with the sponsor medical monitor or designee (eg, Grade 2 chemotherapy-induced neuropathy).
5.Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive brain metastases may be included in the study. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy or stereotactic radiotherapy and study enrolment.
6.Active primary immunodeficiency, known HIV infection, or active hepatitis B or C infection. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Participants should be tested for HIV prior to randomisation/enrolment if required by local regulations or IRB/EC.
7.Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
8.Receipt of live, attenuated vaccine within 30 days prior to the first dose of study drug. Note: Participants, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of study treatment.
9.Participants with a medical history of myocardial infarction within 6 months before randomisation or symptomatic CHF (NYHA Class II to IV). Participants with troponin levels above upper limit of normal (ULN) at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before enrolment to rule out myocardial infarction.
10.Investigator judgment of 1 or more of the following:
(a)Q
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method