A Pilot Trial of Platinum, Gemcitabine, or Pemetrexed Single- or Multi-Agent Therapy With Serial Tumor Specimen Collection in Patients With Advanced Non-Small-Cell Lung Cancer
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Baseline Marker Measurement
研究概览
简要总结
This pilot clinical trial studies whether the levels of certain genes in the tissue and blood are related to how well patients with stage IV non-small cell lung cancer respond to chemotherapy. Genes may affect how sensitive or resistant tumors are to chemotherapy. Studying the levels of genes related to tumor response before and after chemotherapy may help doctors learn whether they can predict how well patients will respond to treatment.
详细描述
PRIMARY OBJECTIVES:
I. To describe the association between baseline gene expression levels at the protein and messenger ribonucleic acid (mRNA) level and best treatment response after two cycles of single-agent or multi-agent chemotherapy
SECONDARY OBJECTIVES:
I. To describe changes in protein and mRNA levels of ribonucleotide reductase M1 (RRM1), thymidylate synthetase (TS), and excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1) in serial biopsies obtained from patients being treated with gemcitabine (gemcitabine hydrochloride), pemetrexed (pemetrexed disodium), and platinum.
II. To describe the association between changes in marker levels and changes in tumor diameters.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 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
- •Patients with advanced stage NSCLC who are candidates for single or multi-agent first-line therapy.
- •Second-line or higher therapy for any patients with NSCLC with performance status (PS) 0-2
- •Maintenance therapy for patients after completion of four cycles of dual-agent platinum-based chemotherapy
- •Stage IV, histologically or cytologically confirmed NSCLC; confirmation may be obtained with the first protocol-specified tumor biopsy
- •White blood cell count > 3000/mm^3
- •Platelet count > 100,000/mm^3
- •Hemoglobin > 9.0 g/dl
- •A tumor lesion that can be safely biopsied as judged by the treating oncologist and physician performing the procedure and has not been radiated
- •At least one unidimensionally measurable tumor lesion >= 1 cm in longest diameter using spiral CT (>= 2 cm in longest diameter by any other technique) that has not been radiated and is not located in a bone
- •Performance status 0-2 by Eastern Cooperative Oncology Group criteria
- •Life expectancy of >= 3 months
- •Able to understand and sign the informed consent document
排除标准
- •Therapy that does not include cisplatin, carboplatin, gemcitabine, and/or pemetrexed
- •Concomitant medical or psychiatric illness that is likely to interfere with a reasonably safe execution of the treatment plan
- •Concomitant malignancy other than NSCLC that requires active therapy; prior malignancies are allowed as long as the disease is controlled and does not require ongoing therapy of any kind; prior therapy must have concluded at least 1 year before treatment initiation on this protocol; exceptions are non-melanoma skin cancer, prostate cancer and prostatic intraepithelial neoplasia (PIN) treated with local intervention and deemed cured, cervical cancer and carcinoma in situ (CIS) treated with local intervention and deemed cured, and laryngeal cancer and CIS treated with local intervention and deemed cured
- •Carcinomatous meningitis
- •Uncontrolled central nervous system (CNS) disease
- •The time interval between CNS radiation, whole brain radiation, spinal cord radiation, or radiosurgery, and initiation of protocol specified chemotherapy must be at least 1 week
- •Malignant pleural, pericardial, or peritoneal effusion if it is the only site of disease activity; i.e., if no other measurable tumor lesions exist
- •Coagulopathy or anticoagulation therapy that cannot be safely corrected or interrupted for tumor biopsy
- •Significant hepatic dysfunction, renal dysfunction, or metabolic derangement that precludes full-dose chemotherapy at the specified starting doses
- •Concomitant treatment with chemotherapeutic agents for diseases other than malignancy
- •Pregnancy or lactation
研究组 & 干预措施
Treatment (chemotherapy regimen)
Patients receive 1 of 4 chemotherapy regimens at the discretion of the primary oncologist following institutional guidelines, including cisplatin, carboplatin, pemetrexed disodium IV on day 1, or gemcitabine hydrochloride IV on days 1 and 8. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. After course 2, patients may continue treatment off-study at the discretion of the treating physician.
干预措施: docetaxel (Drug)
Treatment (chemotherapy regimen)
Patients receive 1 of 4 chemotherapy regimens at the discretion of the primary oncologist following institutional guidelines, including cisplatin, carboplatin, pemetrexed disodium IV on day 1, or gemcitabine hydrochloride IV on days 1 and 8. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. After course 2, patients may continue treatment off-study at the discretion of the treating physician.
干预措施: pemetrexed disodium (Drug)
Treatment (chemotherapy regimen)
Patients receive 1 of 4 chemotherapy regimens at the discretion of the primary oncologist following institutional guidelines, including cisplatin, carboplatin, pemetrexed disodium IV on day 1, or gemcitabine hydrochloride IV on days 1 and 8. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. After course 2, patients may continue treatment off-study at the discretion of the treating physician.
干预措施: gemcitabine hydrochloride (Drug)
Treatment (chemotherapy regimen)
Patients receive 1 of 4 chemotherapy regimens at the discretion of the primary oncologist following institutional guidelines, including cisplatin, carboplatin, pemetrexed disodium IV on day 1, or gemcitabine hydrochloride IV on days 1 and 8. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. After course 2, patients may continue treatment off-study at the discretion of the treating physician.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Baseline Marker Measurement
时间窗: Baseline
A univariable regression of continuous disease response on baseline marker value will be performed. A multivariable regression model adjusted for clinical covariates will be evaluated as well. Expression levels of RRM1, TS, BRCA1, and other molecules and disease response after course 2 will be log-transformed.
次要结局
- Change in Biomarker Expression Levels(Baseline to up to 8 weeks (after course 2))
- Overall Survival (OS)(From the date of protocol-specified treatment initiation to the date of death or last observation, assessed up to 12 months)
- Expression Levels of Biomarkers and Other Molecules(Up to 8 weeks (end of course 2))
- Progression-free Survival (PFS)(From the date of protocol-specified treatment initiation to the date of progression, death, or last observation, assessed up to 12 months)
研究者
Gerold Bepler
Principal Investigator
Barbara Ann Karmanos Cancer Institute