A Phase II Randomized Window of Opportunity Trial Evaluating Clinical and Biological Effects of Intratumoral INT230-6 in Early Stage Breast Cancer: The INVINCIBLE Trial
试验速览
- 阶段
- 2 期
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- The proportion of patients achieving a CCCA defined as a reduction in the proportion of cells staining positive for Ki67 as assessed by immunohistochemistry to less than a natural logarithm, or ≤2.7%, at the post-treatment specimen.
研究概览
简要总结
This is a phase II, randomized, multi-center, parallel design, window of opportunity trial evaluating intratumoral INT230-6 in up to 90 patients with early stage breast cancer. In a 2:1 randomization, patients on the treatment arm will receive intratumoral INT230-6 injections prior to breast surgery.
详细描述
The study comprises 2 consecutive parts. The first part will be to test safety and feasibility of the dosing procedures. Results from Part I of the study will standardise the optimal dose and frequency of INT230-6 for participants in Part II.
Part I: Open-label 2:1 randomized study of up to 30 patients. Treatment arm patients will be given up to 3 doses of INT230-6 injected weekly prior to breast surgery, at a dose based on longest diameter. The control arm patients receive no treatment.
Part II: Double-blind, 2:1 randomized study of up to an additional 60 patients. The placebo arm includes a saline injection of similar dose and frequency as the treatment arm (up to 2 doses of INT230-6/saline injected weekly prior to breast surgery).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Female patients with newly diagnosed histologically confirmed primary invasive breast cancer currently not undergoing any treatment while awaiting surgery.
- •Patients with early, operable stage I to II breast cancer amendable for complete surgical resection as assessed by treating surgical oncologist.
- •Tumors must be clinically palpable by surgeon. Part I: ≥ 1.0 cm by palpation or on imaging. Part II: ≥ 1.5 cm by palpation or on imaging.
- •Histologic Bloom Richardson grade ≥
- •Invasive ductal or lobular carcinoma, invasive carcinoma Not Otherwise Specified (NOS).
- •ECOG PS 0-2 (Appendix A).
- •The participant (or legally acceptable representative if applicable) is able to provide written informed consent for the study.
排除标准
- •Locally advanced or metastatic breast cancer.
- •Prior therapy with chemotherapy or planned neoadjuvant chemotherapy.
- •Pre-dominant histology other than invasive ductal or lobular carcinoma or invasive carcinoma NOS.
- •Patients with an active infection.
- •Absolute Neutrophil Count < 1.5 x 10^9/L.
- •Patients with pre-existing renal impairment, Creatinine clearance calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation of less than 50 mL/min/1.73m
- •Any serious known immediate or delayed hypersensitivity reaction(s) to vinblastine or cisplatin or idiosyncrasy to drugs chemically related to the investigational drugs.
- •Known allergic reaction to local anesthetic (Xylocaine, Marcaine).
- •Concurrent medical condition requiring the use of immunosuppressive medications, or systemic corticosteroids at doses of greater than 10 mg Prednisone-equivalent Topical steroids and other localized corticosteroids are permitted. Use of steroids as prophylactic treatment for subjects with contrast allergies to diagnostic imaging contrast dyes will be permitted.
- •Concurrent use of a prohibited medication or planned use of any forbidden medications during treatment with INT230-6, or within 4 weeks prior to study drug administration, which include chemotherapy, immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer: systemic or intratumoral), other biologic therapy, investigational therapy, or hormonal therapy, cisplatin containing agents, and vinblastine containing agents while on treatment in this study. Other prohibited concomitant medications that will interact with vinblastine and cisplatin include mitomycin, phenytoin, CYP3A4 inhibitors (ketoconazole, voriconazole, clarithromycin, erythromycin), nephrotoxic drugs (aminoglycosides, amphotericin), or pure pyridoxine (pyridoxine contained in multivitamin is permitted). Use of other investigational drugs (drugs not marketed for any indication) within 4 weeks prior to study drug administration not permitted.
- •Pregnancy if patient is of childbearing age) or breast feeding.
- •Subjects with signs/symptoms suggestive of COVID-19 or known COVID-19 positive contacts in the past 14 days would be tested as per local Public Health and/or Institutional Guidelines. If patients are COVID-19 positive at the time of screening, they would be excluded from the trial.
- •Any underlying medical condition that, in the Principal Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity determination or adverse events, or renders the patient ineligible to be on study.
研究组 & 干预措施
INT230-6 Treated Arm
Part I: Patients will receive up to 3 doses of INT230-6 injected weekly prior to breast surgery
Part II: Patients will receive up to 2 intratumoral doses of INT230-6 (over a 15-day period) prior to breast surgery
干预措施: Saline injection (Other)
INT230-6 Treated Arm
Part I: Patients will receive up to 3 doses of INT230-6 injected weekly prior to breast surgery
Part II: Patients will receive up to 2 intratumoral doses of INT230-6 (over a 15-day period) prior to breast surgery
干预措施: INT230-6 (Drug)
Control Arm
Part I: No intervention while awaiting surgery
Part II: Placebo saline injection
干预措施: Saline injection (Other)
结局指标
主要结局
The proportion of patients achieving a CCCA defined as a reduction in the proportion of cells staining positive for Ki67 as assessed by immunohistochemistry to less than a natural logarithm, or ≤2.7%, at the post-treatment specimen.
时间窗: presurgical window (period from diagnosis to surgery window of 3-6 weeks)
Tumor's viable plus necrotic tissue, at the post-treatment specimen.
次要结局
- Adverse effects of INT230-6 injected to breast cancers in healthy patients prior to surgery.(presurgical window (period from diagnosis to surgery of 3-6 weeks))
- Markers of immunomodulation including macrophages, NK, DC, CD4 T-cells, CD8 T-cells, regulatory T-cells.(presurgical window (period from diagnosis to surgery of 3-6 weeks))
- The proportion of patients that achieved a complete pathologic response on surgical pathology as measured by the residual cancer burden index(presurgical window (period from diagnosis to surgery of 3-6 weeks))
- Immunohistochemical and gene expression markers of necrosis, apoptosis and tumor proliferation pathways.(presurgical window (period from diagnosis to surgery of 3-6 weeks))