Efficacy of metronomic oral capecitabine, methotrexate and cyclophosphamide in locally advanced operable oral cavity squamous cell carcinoma - A Phase II study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Among patients diagnosed with operable locally advanced oral cavity squamous cell cancer and receiving metronomic chemotherapy
研究概览
简要总结
Background
Head and neck squamous cell carcinoma (HNSCC) is one of the country’s most common cancers[1]. More than half of the patients present in the advanced stage[2,3]. HNSCC can be treated with surgery and/or chemoradiotherapy in about two thirds of cases. For oral cavity cancers, the preferred modality of treatment is primary surgery. Subsequently patients receive adjuvant radiation or chemoradiation depending on the risk status. Currently, locally advanced tumor stages III and IV, local recurrences or distant metastases occur in about 40-60% of patients.
Metronomic chemotherapy, continuous and dose-dense administration of chemotherapeutic drugs with lowered doses, is being evaluated for substituting, augmenting, or appending conventional maximum tolerated dose regimens, with preclinical and clinical studies for the past few decades. To date, the principle mechanisms of its action include impeding tumoral angiogenesis and modulation of hosts’ immune system, directly affecting tumor cells, their progenitors, and neighboring stromal cells. Its better toxicity profile, lower cost, and easier use are main advantages over conventional therapies. The evidence of metronomic chemotherapy for personalized medicine is growing.
Rationale
Neoadjuvant chemotherapy has been tried in HNSCC in multiple settings, but has never been consistently shown to improve survival. In locally advanced/borderline resectable head and neck cancers, neoadjuvant chemotherapy followed by reassessment for surgery is an option as in developing countries like India due to huge patient burden all patients can not be accommodated for surgery in time and there is a long waiting period. But the usual platinum-based neoadjuvant chemotherapy is also not a standard treatment option and it has a high toxicity profile and significant mortality. It also causes nutritional depletion of patients.
Novelty
The effect of metronomic chemotherapy in a form of oral capecitabine, methotrexate and cyclophosphamide in a preoperative setting has not been explored earlier.
Expected Outcome
This study aims to evaluate the clinical response of locally advanced oral cavity cancer after administering two cycles of oral metronomic chemotherapy in a form of oral capecitabine, methotrexate and cyclophosphamide, toxicities of the oral metronomic chemotherapy schedule and also its effect on the post surgery 30 days morbidity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Not Applicable
- 盲法
- Not Applicable
入排标准
- 年龄范围
- 18.00 Year(s) 至 90.00 Year(s)（—）
- 性别
- All
入选标准
- •Age > 18 years Biopsy proven Operable locally advanced oral cavity squamous cell carcinoma(T4a/4b NanyM0) ECOG performance status 0-2 WBC count≥ 3 × 109 /L with neutrophils ≥ 1.5 × 109/L , platelet count ≥ 1 lakh/mL and Hb ≥ 9 gm/dL Total Bilirubin ≤ 1.5 times the upper limit of normal range AST & ALT ≤ 5 times the upper limit of normal range Patients with measurable disease by RECIST 1.1 criteria.
排除标准
- •Inoperable oral cavity carcinoma [Skull base invasion, prevertebral fascia involvement or carotid encasement] Metastatic oral cavity carcinoma Recurrent oral cavity carcinoma.
结局指标
主要结局
Among patients diagnosed with operable locally advanced oral cavity squamous cell cancer and receiving metronomic chemotherapy
时间窗: In every 2 weeks of therapy response will be assessed clinically as per RECIST 1.1. | Toxicity will be assessed at Day 8, Day 15, Day 28, and Day 56 of the therapy.
To assess the clinical benefit rate
时间窗: In every 2 weeks of therapy response will be assessed clinically as per RECIST 1.1. | Toxicity will be assessed at Day 8, Day 15, Day 28, and Day 56 of the therapy.
To assess the toxicity as graded by CTCAE ver 5.0
时间窗: In every 2 weeks of therapy response will be assessed clinically as per RECIST 1.1. | Toxicity will be assessed at Day 8, Day 15, Day 28, and Day 56 of the therapy.
次要结局
- 1.To assess the 30 days post surgical morbidity as graded by Clavien Dindo classification(2.To assess the clinicopathological factors and pre-treatment VEGF gene expression with response)