A Study of Dato-DXd Versus ICC in Inoperable or Metastatic HR-positive, HER2-negative Breast Cancer
- Conditions
- Breast Cancer
- Registration Number
- JPRN-jRCT2031210440
- Lead Sponsor
- Inoguchi Akihiro
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 700
Age
1. Participant must be >= 18 years
Type of Participant and Disease Characteristics
2. Inoperable or metastatic HR-positive, HER2-negative breast cancer (per ASCO/CAP guidelines, on local laboratory results); ie, is documented as HR-positive (either ER and/or PgR positive [ER or PgR >= 1%]) and HER2-negative. If a participant had multiple results after metastatic disease, the most recent local test result will be used to confirm eligibility.
3. Progressed on or not suitable for endocrine therapy per investigator assessment, and treated with 1 to 2 lines of prior standard of care chemotherapy in the inoperable/metastatic setting. Participant must have documented progression on their most recent line of chemotherapy.
Note: If a chemotherapy drug is changed within 28 days of use to another drug in the same class (ie, antimetabolite to antimetabolite) for any reason, the first drug is not counted as a line. Targeted agents (such as mTOR inhibitors, PD-1/PD-L1 inhibitors, PARP inhibitors), endocrine therapies, and CDK4/6 inhibitors on their own do not contribute to the count of prior lines of chemotherapy; however, regimens with such agents in combination with metastatic chemotherapy should be classified as one line of chemotherapy.
4. Eligible for one of the chemotherapy options listed as ICC (eribulin, capecitabine, vinorelbine, gemcitabine), per investigator assessment. Note: Participants who previously received any of these agents are eligible for enrolment to another ICC agent in this study.
5. ECOG PS of 0 or 1, with no deterioration over the previous 2 weeks prior to day of first dosing.
6. At least 1 measurable lesion not previously irradiated that qualifies as a RECIST 1.1. Target Lesion at baseline and can be accurately measured at baseline as >= 10 mm in the longest diameter (except lymph nodes, which must have short axis >= 15 mm) with CT or MRI, which is suitable for accurate repeated measurements.
Note: Participants with bone-only metastases are not permitted.
7. Participants with a history of previously treated neoplastic spinal cord compression, or clinically inactive brain metastases, 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 radiotherapy and study enrolment.
8. Adequate organ and bone marrow function within 7 days before day of first dosing as
follows:
- Hemoglobin: >= 9.0 g/dL. Red blood cell/plasma transfusion is not permitted within 1 week prior to screening assessment.
- Absolute neutrophil count:>= 1500/mm^3
. Granulocyte colony-stimulating factor administration is not permitted within 1 week prior to screening assessment.
- Platelet count: >= 100000/mm^3. Platelet transfusion is not permitted within 1 week prior to screening assessment.
- Total bilirubin: <= 1.5 x ULN if no liver metastases; or <=3 x ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline.
- ALT and AST: <= 3 x ULN for AST/ALT; however, if elevation is due to liver metastases, <= 5.0 x ULN is allowed.
- Calculated creatinine clearance: >= 30 mL/min as calculated using the Cockcroft- Gault equation (using actual body weight): Female: CrCl = Weight (kg) x (140 - Age) x 0.85 (mL/min) 72 x serum creatinine (mg/dL)
Male: CrCl = Weight (kg) x (140 - Age) (mL/min) 72 x serum creatinine (mg/dL)
9. LVEF >= 50%
1. As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, uncontrolled hypertension, history of allogeneic organ transplant, and active bleeding diseases, ongoing or active infection, or significant or cardiac or psychological conditions) which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.
2. 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 intervention 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, or other solid tumors curatively treated.
3. Persistent toxicities caused by previous anticancer therapy (excluding alopecia), not yet improved to CTCAE Version 5.0 Grade <= 1 or baseline. Note: participants may be enrolled with some chronic, stable Grade 2 toxicities (defined as no worsening to > Grade 2 for at least 3 months prior to first dosing and managed with SoC treatment) which the investigator deems related to previous anticancer therapy, including (but not limited to):
- Chemotherapy-induced neuropathy.
- Fatigue.
- Residual toxicities from prior immunotherapy treatment: Grade 1 or Grade 2
endocrinopathies which may include:
o Hypothyroidism/hyperthyroidism.
o Type I diabetes.
o Hyperglycaemia.
o Adrenal insufficiency
o Adrenalitis.
- Skin hypopigmentation (vitiligo).
4. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections.
Note: Participants with localized fungal infections of skin or nails are eligible.
5. Known active or uncontrolled hepatitis B or C infection. Participants are eligible if they:
a. Have been curatively treated for HCV infection as demonstrated clinically and by viral serologies
b. Have received HBV vaccination with only anti-HBs positivity and no clinical signs of hepatitis
c. Are HBsAg- and anti-HBc+ (i.e., those who have cleared HBV after infection) and meet conditions i-iii below:
d. Are HBsAg+ with chronic HBV infection (lasting 6 months or longer) and meet conditions i-iii below:
i. HBV DNA viral load < 2000 IU/mL
ii. Have normal transaminase values, or, if liver metastases are present, abnormal transaminases, with a result of AST/ALT <3 x ULN, which are not attributable to HBV infection
iii. Start or maintain antiviral treatment if clinically indicated as per the investigator
6. Known HIV infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA, CD4+ count > 350 cells/mm3, no history of AIDs-defining opportunistic infection within the past 12 months, and stable for at least 4 weeks on same anti-HIV retroviral medications (meaning there are no expected further changes in that time to the number or type of antiretroviral drugs in the regimen). If an HIV infection meets the above criteria, monitoring of viral RNA load and CD4+ count is recommended. Participants must be tested for HIV if acceptable by local regulations or an IRB/EC.
7. Uncontrolled or significant cardiac disease, including myocardial infarction or uncon
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1. Progression Free Survival [ Time Frame: From randomization until progression as assessed by BICR or death due to any cause (anticipated to be 21 months) ]<br>PFS is defined as time from randomization until progression per RECIST 1.1, as assessed by BICR, or death due to any cause. The analysis will include all randomized participants as randomized regardless of whether the participant withdraws from therapy, receives another anti-cancer therapy, or clinically progresses prior to RECIST 1.1. The measure of interest is the hazard ratio of PFS.<br><br>2. Overall Survival [ Time Frame: Approximately 44 months ]<br>OS is defined as time from randomization until the date of death due to any cause. The comparison will include all randomized participants as randomized, regardless of whether the participant withdraws from therapy or receives another anti-cancer therapy. The measure of interest is the hazard ratio of OS.
- Secondary Outcome Measures
Name Time Method