A Phase IB Randomized Translational Study of Fenretinide (4-HPR) in Combination With SCH66336, a Farnesyl Transferase Inhibitor, in Patients With Advanced or Recurrent Head and Neck Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
The primary objective of this study is to estimate the modulation of intermediate biological endpoints of the combination of 4-HPR and SCH66336, a farnesyl transferase inhibitor (FTI), across 4 randomly assigned dose levels in patients with locally advanced or recurrent head and neck cancer. We will also assess the activity, safety, tolerability and side effects of 4-HPR/SCH66336 and hope to establish a phase II regimen.
详细描述
The drug fenretinide is a retinoid that is similar to vitamin A. It is believed that fenretinide can cause cancer cells to die. SCH66336 is a drug that blocks farnesyl protein transferase (a substance needed by cancer cells to grow). It is believed that SCH66336 may selectively stop cancer cells from growing while not affecting normal cells.
Both SCH66336 and fenretinide are taken orally and must be swallowed whole (i.e., the drugs may not be broken to make swallowing easier). Individuals who cannot take the study medications whole by mouth cannot enroll in this study.
In this study participants will receive SCH66336 twice a day for each day of a 21-day cycle. Participants will also take fenretinide twice a day on Days 1-7 of the same cycle. Before beginning treatment, participants will have a complete physical exam, including measurement of height, weight, and vital signs. Participants will have blood and urine tests, a chest x-ray, and an ECG (heart function test). Females who are able to become pregnant must have a negative blood pregnancy test. In addition, all participants will have a neurological exam and will complete a questionnaire about their night vision. Some individuals may need an eye exam.
Before beginning treatment, participants will have a biopsy of their tumor and will provide a sample of their buccal mucosa (inner cheek). In the biopsy, a sample of tumor tissue will be removed with a large needle. The buccal mucosa sample will be obtained by scraping the inside of the cheek. Participants will also have an extra blood sample (about 2 tablespoons) drawn. The tumor, buccal mucosa, and blood samples are all being obtained for research purposes only and will not directly benefit the participant.
During the study, a physician will examine participants at least once a week for the first cycle of treatment. A treatment cycle is 3 weeks. Participants will also have weekly blood tests. After the first cycle of treatment, participants will have exams every 3 weeks. In addition, participants will have urine tests every 3 weeks, a neurological exam after the first 3 weeks and then as needed, and a chest x-ray every 3 weeks. Every 3 months, participants will complete a questionnaire about their night vision and will have an eye exam, if needed.
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
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient has histologically proven squamous cell carcinoma of the head and neck which is biopsy accessible and is not considered curable by standard measures.
- •Patient has a Karnofsky performance status >/= 70%
- •Patient has adequate bone marrow function: *WBC >/= 3,000 cells/mm^3, *ANC >/= 1,500 cells/mm^3, *platelet count >/= 100,000 cells/mm^3, *Hgb >/= 9.0 g/dL.
- •Patient has adequate liver function: *total bilirubin level </= 2.0 mg/dL, *albumin >/= 2.5 g/dL.
- •Transaminases (SGOT and/or SGPT) may be up to 2.5 x ULN if alkaline phosphatase is </= ULN, or alkaline phosphatase may be up to 4 x ULN if transaminases are </= ULN.
- •Patient has adequate renal function: a serum creatinine < 2 mg/dl
- •Patient has signed a written informed consent.
- •Patient has received no more than 2 prior chemotherapeutic regimens for recurrent or metastatic disease. Prior biologic therapy is not included.
排除标准
- •Patient has received 3 or more prior chemotherapeutic regimens for recurrent/metastatic disease.
- •No biopsy accessible tissue.
- •Patient has received radiation therapy within the past 6 months.
- •Prior radiation to the biopsy site.
- •Patient has signs or symptoms of acute infection requiring systemic therapy.
- •Patient exhibits confusion, disorientation, or has a history of major psychiatric illness which may impair patient's understanding of the informed consent.
- •Patient has grade 3 or 4 neurotoxicity from previous anticancer treatment or significant neuropathy from any cause.
- •Patient requires total parenteral nutrition with lipids.
- •Surgery is anticipated to leave patient unable to swallow the SCH66336 or 4-HPR daily.
- •Patient has a history of uncontrolled heart disease (including arrhythmia, angina, congestive heart failure, or any heart condition that cannot be controlled with regular ongoing medication)
- •Because of the known teratogenic effect of retinoids, pregnant women and women who are currently breast-feeding may not participate in this study. All women of childbearing potential must have a negative pregnancy test within 24 hours prior to enrolling in the study.
- •Serious infection or other intercurrent illness requiring immediate therapy.
- •Inability to swallow oral medications, or other medical or social factors interfering with compliance.
- •Patients may not take high dose synthetic or natural Vitamin A derivatives (>10,000 IU per day). Patients may not be taking high-dose vitamin A within 30 days of study entry.
- •Patients should not take any anti-oxidants such as Vitamin E or Vitamin C
- •Patients with pre-existing retinopathy
研究组 & 干预措施
4-HPR + FTI
SCH66336 daily for 21 days each cycle and with 4-HPR daily on days 1-7 only. On day 1 of cycle 1, 4-HPR only beginning SCH66336 on day 2 of cycle 1.
干预措施: Fenretinide (4-HPR) (Drug)
4-HPR + FTI
SCH66336 daily for 21 days each cycle and with 4-HPR daily on days 1-7 only. On day 1 of cycle 1, 4-HPR only beginning SCH66336 on day 2 of cycle 1.
干预措施: SCH66336 (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: 21 day courses
MTD derived from lack of dose limiting toxicities (DLT) in 4 differing dose levels.
次要结局
未报告次要终点