A Phase II Randomized Trial of Neoadjuvant Chemotherapy With or Without Triple Oral Metronomic Chemotherapy and Low-Dose Immunotherapy in Resectable Locally Advanced Penile Squamous Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Pathological complete response rate (pCR)
研究概览
简要总结
Aim: To evaluate the efficacy and impact on survival with neoadjuvant chemotherapy with or without triple oral metronomic chemotherapy and low-dose immunotherapy in resectablelocally advanced penile squamous cell carcinoma
**Primary Objective:**Pathological complete response rate (pCR)
Secondary Objectives**:** Event free survival (EFS), Overall Survival (OS), Lymph node pathological complete response rate, Patterns of treatment failure, Quality of Life (QOL), Safety, Treatment completion rates, Objective Response Rate (ORR), R0 resection rates, Postoperative complication rates
**Tertiary Objectives:**Exploring biomarkers
**Treatment Plan:**Eligible patients will be randomized in a 1:1 manner to doublet neoadjuvant chemotherapy (Paclitaxel, Carboplatin) plus triple oral metronomic chemotherapy (methotrexate, erlotinib, celecoxib), and low-dose immunotherapy (nivolumab) or neoadjuvant doublet or triplet chemotherapy (taxane and platinum, or taxane, platinum, and ifosfamide) alone. Patients will be assessed for definitive therapy (surgery and/or radiation) after completion of neoadjuvant therapy. After definitive therapy, patients will be followed-up every 2-3 months until progressive disease or unacceptable treatment related toxicity. Following progression or discontinuation, patients will be followed up and treated as per the discretion of the treating physician or as per standard institutional protocol.
**Interim analysis (If recommended by the ethics committee):**A single interim analysis will be conducted after ~50 patients have evaluable pCR data. Early stopping for efficacy will be considered if the one-sided p value is less than or equal to 0.005. Futility will be declared if conditional power is less than 20% under both planned and observed assumptions (or is less than or equal to 10% under observed trend). The trial may be paused/stopped for safety if the absolute increase in grade is more than or equal to3 AE rate in Arm A vs Arm B exceeds 25 percentage points and is judged clinically unacceptable.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 80.00 Year(s)（—）
- 性别
- Male
入选标准
- •Subjects must be treatment naïve and have histologically proven squamous cell carcinoma of the penis.
- •The tumour should be surgically resectable, and patients referred for neoadjuvant treatment after a multidisciplinary joint clinic decision will be included.
- •Prior local treatment for the primary tumour will be permitted if deemed appropriate by the multidisciplinary team.
- •Male or transgender subjects aged 18 years and above.
- •Eastern Cooperative Oncology Group (ECOG) performance status between 0 and
- •Subjects must have normal organ and marrow function and all the counts are in the normal range Patients with HIV are eligible if their CD4 count is above 200, they are on HAART therapy, and there are no active AIDS-defining conditions.
- •Subjects must agree to use effective contraception during the study and for three months after completion of treatment.
- •Men of all races and ethnic groups are eligible for this study.
- •Ability to understand and willingness to sign a written informed consent document.
- •Subjects must agree to use highly effective contraception throughout the study and for at least 30 days after the last dose of Nivolumab, as the drug may be harmful to a developing foetus.
- •Willingness to comply with all study requirements and procedures.
排除标准
- •Subjects who are receiving any other investigational agents.
- •Presence of clinical or radiological evidence of metastatic disease.
- •Patients who are unfit for curative surgery for any reason.
- •Active infection requiring systemic therapy.
- •Hepatitis B or C infection at screening with a raised viral load (HBV DNA or HCV RNA).
- •Known severe hypersensitivity to the study drug or its components.
- •Clinically significant cardiovascular disease such as unstable angina, congestive heart failure of New York Heart Association Class II or higher, serious uncontrolled arrhythmia, or an ejection fraction less than 50 percent.
- •Presence of severe acute or chronic medical or psychiatric conditions such as inflammatory bowel disease, pneumonitis, chronic kidney disease, chronic liver disease, pulmonary fibrosis, peripheral neuropathy of grade more than one, or active suicidal ideation or behaviour.
- •History of any other malignancy within the past three years except curatively treated basal cell carcinoma of the skin.
- •Current use of immunosuppressive medication except for local, inhaled, or topical steroids, systemic corticosteroids at physiologic doses of ten milligrams or less of prednisone or equivalent, steroids as premedication for scans or emesis, or steroids used for raised intracranial pressure due to disease.
- •Active autoimmune disease that could worsen with chemotherapy.
- •Patients with type 1 diabetes, vitiligo, psoriasis, or thyroid disorders not requiring immunosuppressive treatment are eligible.
- •History of organ or allogeneic stem-cell transplantation.
- •Vaccination within four weeks prior to the first dose of Nivolumab and during the study period, except for administration of inactivated vaccines.
结局指标
主要结局
Pathological complete response rate (pCR)
时间窗: 4 years
次要结局
- Event free survival (EFS), Overall Survival (OS), Lymph node pathological complete response rate, Patterns of treatment failure, Quality of Life (QOL), Safety, Treatment completion rates, Objective Response Rate (ORR), R0 resection rates, Postoperative complication rates(4 years)
研究者
Dr Minit Shah
Tata Memorial Hospital