A Phase II Trial Evaluating the Combination of Carboplatin, Gemcitabine, and Capecitabine in Patients With Carcinoma of Unknown Primary Site
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 试验地点
- 2
研究概览
简要总结
This study is for patients with a type of cancer called carcinoma of unknown primary site (CUP), meaning that the site of the body where the tumor has originated is not clear. Currently, carcinoma of unknown primary site (CUP) accounts for about 5% of all newly diagnosed malignancies. The stage of the tumor is such that it is not treatable by surgery. Currently, the standard treatment for such a type of cancer at that stage is chemotherapy. However, the overall prognosis for patients with metastatic CUP remains poor, even if treated with conventional chemotherapy. Through ongoing research at medical centers around the world, doctors are trying to improve on the presently available chemotherapy regimens. The purpose of the investigators' study is similar: it is trying to determine whether a combination of three chemotherapy drugs - carboplatin, gemcitabine, and capecitabine - will improve the treatment of patients with metastatic CUP. The reason the investigators are interested in the above combination of chemotherapy agents is that each one of them is already used in patients with a variety of specific tumors, such as lung cancer, breast cancer, pancreatic cancer, colon cancer, etc.
This research study will help determine whether the combination of carboplatin, gemcitabine and capecitabine can be used and is effective in patients with carcinoma of unknown primary site.
详细描述
Carcinoma of unknown primary site (CUP) accounts for approximately 5% of all newly diagnosed malignancies. The overall prognosis for patients with CUP remains poor, with median survival less than one year with modern chemotherapy combinations and virtually no long-term survivors.
It has been recognized that patients with CUP represent a heterogeneous group of tumors. Managing patients with CUP requires a complete medical history, careful consideration of findings on physical exam, targeted radiologic studies and pathologic analysis of biopsy and/or surgical specimens. Within this heterogeneous group there exist at least four subsets of patients with CUP, that based on clinicopathologic features are treated with regimens which have demonstrated efficacy in tumors originating in the most likely primary site of that CUP; squamous carcinoma involving mid or high levels of cervical lymph nodes, women with isolated axillary adenopathy containing adenocarcinoma, women with a predominant presentation of peritoneal carcinomatosis and young men with extragonadal germ cell syndrome.
Unfortunately, a majority of patients with CUP do not fall into any of the above subsets and these represent a therapeutic dilemma, as there is no single regimen to date that has shown significant activity or has resulted in prolonged survival for these patients with particularly poor prognosis. Thus, new therapeutic combinations need to be investigated for treatment of these patients with CUP.
Platinum compounds have been the cornerstone of chemotherapy regimens for a wide variety of solid tumors, including lung, urothelial, head and neck, ovarian and endometrial carcinomas, as well as testicular carcinomas. Cisplatin and its analog carboplatin are currently used in chemotherapy combinations to treat CUP. Carboplatin has fewer non-hematologic side effects compared to cisplatin including less nausea and vomiting, peripheral neuropathy, nephrotoxicity and ototoxicity making it an attractive agent to combine with other drugs.
In recent years, new agents active in solid malignancies have been developed. Gemcitabine is one such agent. It is a deoxycytidine analogue structurally related to cytosine arabinoside. Gemcitabine is activated by deoxycytidine kinase in three steps of phosphorylation into difluorodeoxycytidine triphosphate, which when incorporated into DNA, leads to chain termination. Gemcitabine has been shown to have activity in pancreatic, breast, non-small cell lung carcinomas as well as in carcinomas of unknown primary site. Because of its mild toxicity profile, gemcitabine has been used in combination with other chemotherapy agents. There is evidence of in vitro and in vivo synergy between gemcitabine and the platinum compounds.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologic or cytologic diagnosis of carcinoma, with clinical evidence of metastasis and the primary site not clear after the following work-up:
- •Complete history and physical
- •Laboratory evaluation including serum beta-human chorionic gonadotropin (HCG), serum alpha-fetoprotein for undifferentiated or poorly differentiated carcinomas and serum prostate specific antigen (PSA) in men.
- •Directed radiologic evaluation including, at a minimum, computerized tomography (CT) of chest, abdomen and pelvis and bilateral mammography for female patients.
- •Pathologic immunohistochemistry studies of the surgical or biopsy specimen, including studies for estrogen receptor/progesterone receptor and PSA stains when clinically appropriate.
- •Patients must be at least 18 years of age and have a Zubrod performance status 0-
- •Adequate organ function, defined as absolute neutrophil count (ANC) > 1500/ul, platelet count of > 100,000/ul, serum creatinine less than or equal to 2.0 mg/dl, serum bilirubin less than or equal to 1.5 mg/dl.
- •Patients must have measurable disease. (Partial response [PR] - at least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum LD.)
- •Patients may be previously untreated or have received one chemotherapy regimen provided it did not include carboplatin, gemcitabine or capecitabine.
- •Patients must have no serious intercurrent medical or psychiatric illness that would limit their ability to provide informed consent or receive protocol therapy.
- •Patients must be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to the initiation of therapy.
排除标准
- •Patients with previous invasive malignancy within the preceding 5 years are ineligible unless clinicopathologic information regarding the current neoplasm is clearly discordant from prior disease. Patients with non-melanoma skin cancer or in situ cancer of any site are eligible.
- •Patients with brain metastasis are not eligible.
- •No concurrent chemotherapy, biological or radiotherapy is allowed.
- •Pregnant or lactating women are not eligible. Women and men of childbearing potential must agree to use effective contraception throughout the treatment period, and for six months after treatment has been discontinued.
- •The following groups of patients will not be eligible for the study as they represent populations of patients with CUP for whom more specific treatment approaches are available:
- •Patients presenting with squamous carcinoma isolated to middle and high cervical lymph nodes
- •Women presenting with isolated axillary lymphadenopathy
- •Women presenting with predominant peritoneal carcinomatosis
- •Men < 50 years of age presenting with predominant mediastinal and/or retroperitoneal nodal involvement and biopsy showing undifferentiated or poorly differentiated carcinoma.