A Phase II, Randomized, Open-Label Study Evaluating Two Inavolisib Dose Levels in Combination with Fulvestrant in Participants with PIK3CA-Mutated, HR-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 8
- 主要终点
- Confirmed Objective Response Rate (ORR), defined as the proportion of participants with a complete response or partial response on at least two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1
研究概览
简要总结
To evaluate the efficacy and safety of inavolisib 9 mg once a day (QD) in combination with fulvestrant compared with inavolisib 6 mg QD in combination with fulvestrant
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Documented ER+ or PR+ tumor, per ASCO/CAP guidelines
- •Documented HER2-negative tumor, per ASCO/CAP guidelines
- •Disease progression during or after treatment with a combination of cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) and endocrine therapy (ET) in the metastatic setting – Participants must have received no more than one prior line of systemic therapy in the locally advanced (recurrent or progressed) or metastatic setting
- •Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) – Participants with evaluable bone-only disease are not eligible; disease that is limited to bone but has lytic or mixed lytic/blastic lesions and at least one measurable soft tissue component per RECIST v1.1 may be eligible
- •Participants for whom endocrine-based therapy is recommended and treatment with cytotoxic chemotherapy is not indicated (e.g., participants with visceral crisis) at time of entry into the study, as per national or local treatment guidelines
- •Confirmation of biomarker eligibility: presence of ≥ 1 study-eligible PIK3CA mutation
- •Life expectancy of > 6 months
- •Ability, in the investigator’s judgment, and willingness to comply with all study -related procedures, including completion of patient-reported outcomes
排除标准
- •Metaplastic breast cancer
- •Prior treatment with chemotherapy in the recurrent locally advanced/metastatic setting
- •Type 1 diabetes, or Type 2 diabetes requiring ongoing systemic therapy
- •Prior treatment with PI3K/Akt/mTOR inhibitors in the recurrent locally advanced/metastatic setting
- •Symptomatic active lung disease, including pneumonitis
- •Requirement for daily supplemental oxygen
结局指标
主要结局
Confirmed Objective Response Rate (ORR), defined as the proportion of participants with a complete response or partial response on at least two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1
Confirmed Objective Response Rate (ORR), defined as the proportion of participants with a complete response or partial response on at least two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1
Incidence of key inavolisib-associated adverse events, including hyperglycemia, stomatitis/oral mucositis, and diarrhea.
Incidence of key inavolisib-associated adverse events, including hyperglycemia, stomatitis/oral mucositis, and diarrhea.
Severity of key PI3K-inhibition associated adverse events, including hyperglycemia, stomatitis/oral mucositis, and diarrhea as per Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Severity of key PI3K-inhibition associated adverse events, including hyperglycemia, stomatitis/oral mucositis, and diarrhea as per Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
次要结局
- DOR, duration of response, defined as the time from the first occurrence of a confirmed objective response to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1
- TTR, time to response, defined as the time from randomization to first occurrence of a documented objective response as determined by the investigator according to RECIST v1.1
- PFS, progression-free survival, defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first)
- Incidence of treatment discontinuations due to adverse events
- Change from baseline in targeted clinical laboratory test results
- Presence, frequency of occurrence, severity, and/or degree of interference with daily activities of symptomatic treatment toxicities (i.e., diarrhea, nausea, vomiting, decreased appetite, fatigue, mouth sores, and rash), as assessed through use of the National Cancer Institute Patient-Reported outcomes Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE) instrument
- Presence and frequency of occurrence of selected hyperglycemia symptoms (i.e. increased thirst and frequent urination), as assessed through the European Organisation for Research and Treatment of Cancer (EORTC) IL382
- Proportion of participants reporting each response option at each assessment timepoint by treatment arm for treatment side effect bother single-item General Population Question 5 (GP5) from the Functional Assessment of Cancer Therapy-General questionnaire (FACT-G)
- Change from baseline/worsening in symptomatic treatment toxicities and treatment side effect bother as assessed through use of the PRO-CTCAE, EORTC IL382, and FACT-G GP5 item, respectively
研究者
Trial Information System - TISL
Scientific
F. Hoffmann-La Roche AG