NCT02113878已完成1 期
A Phase Ib Study of BKM120 With Weekly Cisplatin and Radiotherapy in High Risk Locally Advanced Squamous Cell Cancer of the Head and Neck
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose of Cisplatin
研究概览
简要总结
This research study is evaluating a drug called buparlisib (BKM120) as a possible treatment for locally advanced head and neck squamous cell cancer.
详细描述
- This phase Ib study is combining standard chemoradiotherapy with weekly cisplatin and BKM120 to assess tolerability of this combination in high risk patients with locally advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN). The investigators will also obtain preliminary information about the efficacy of this treatment.
- The participant will receive the study drug buparlisib once daily, by mouth, for 45 days. The participant will be given a study drug-dosing diary for each cycle. It will include special instructions for taking the study drug at home.
- The investigators are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects, not everyone who participates in this research study will receive the same dose of the study drug. The dose given will depend on the number of participants who have been enrolled in the study before and how well they have tolerated their doses.
- All participants will receive weekly cisplatin injection. Cisplatin will be given intra-venously (IV) on days: (1, 8, 15, 22, 29, 36 and 43) at DFCI.
- All participants will receive daily radiotherapy with intensity-modulated radiotherapy (IMRT) for 7 weeks, delivered at DFCI. IMRT is a type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor. Thin beams of radiation of different intensities are aimed at the tumor from many angles. This type of radiation therapy reduces the damage to healthy tissue near the tumor.
- The investigators would like to keep track of the participant's medical condition. Follow-up will continue every 4 to 12 weeks after the end of treatment for the first year and at the investigator's discretion thereafter.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Stage III/IV, locally advanced, biopsy proven squamous cell cancer of the head and neck that undergo chemoradiation as their primary treatment with curative intent.
- •Oropharynx (HPV positive and HPV negative), hypopharynx, larynx primaries, nasopharynx as well as those with documented SCC of the cervical lymph nodes, with unknown primaries.
- •>10 pack years of tobacco use
- •Age ≥ 18 years
- •ECOG performance status ≤ 2
- •At least one site of measurable disease
- •Adequate bone marrow function as shown by: ANC > 1.5 x 109/L, Platelets >100 x 109/L, Hb >9 g/dL
- •Total calcium (corrected for serum albumin) within normal limits
- •Magnesium ≥ the lower limit of normal
- •Potassium within normal limits for the institution.
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range
- •Serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases are present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome)
- •Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min
- •Serum amylase ≤ ULN
- •Serum lipase ≤ ULN
- •Fasting plasma glucose ≤ 120 mg/dL (6.7 mmol/L)
- •Signed informed consent
排除标准
- •Distant metastatic disease
- •Less than or equal to 10 pack years of tobacco history
- •Received prior chemotherapy
- •Received prior radiation to the head and neck or adjacent anatomical site
- •Received prior treatment with a P13K inhibitor.
- •Known hypersensitivity to BKM120 or to its excipients
- •Acute or chronic liver, renal disease or pancreatitis
- •Mood disorders ≥ CTCAE grade 3
- •Diarrhea ≥ CTCAE grade 2
- •Active cardiac disease
- •History of cardiac dysfunction including any of the following:
- •Patient has poorly
- •Impairment of gastrointestinal (GI) function
- •Currently receiving treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug.
- •Chronic treatment with steroids or another immunosuppressive agent.
- •Herbal medications and certain fruits within 7 days prior to starting study drug.
- •Currently treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug. Please refer to Appendix B for a list of prohibited inhibitors and inducers of CYP3A (Please note that co-treatment with weak inhibitors of CYP3A is allowed).
- •Undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
- •Currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant.
- •Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control.
- •Known diagnosis of human immunodeficiency virus (HIV) infection
- •History of another malignancy within 3 years, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix
研究组 & 干预措施
Dose Level 1
Experimental
- 40 mg BKM120 will be administered orally daily for 45 days. Starting dose 40 mg.
- Cisplatin: Starting Dose 30 mg/m2, given IV, weekly on days: (1, 8, 15, 22, 29, 36 and 43).
- Radiotherapy: All participants will receive daily radiotherapy with intensity-modulated radiotherapy (IMRT) for 7 weeks.
干预措施: BKM120 (Drug)
Dose Level 1
Experimental
- 40 mg BKM120 will be administered orally daily for 45 days. Starting dose 40 mg.
- Cisplatin: Starting Dose 30 mg/m2, given IV, weekly on days: (1, 8, 15, 22, 29, 36 and 43).
- Radiotherapy: All participants will receive daily radiotherapy with intensity-modulated radiotherapy (IMRT) for 7 weeks.
干预措施: Cisplatin (Drug)
Dose Level 1
Experimental
- 40 mg BKM120 will be administered orally daily for 45 days. Starting dose 40 mg.
- Cisplatin: Starting Dose 30 mg/m2, given IV, weekly on days: (1, 8, 15, 22, 29, 36 and 43).
- Radiotherapy: All participants will receive daily radiotherapy with intensity-modulated radiotherapy (IMRT) for 7 weeks.
干预措施: Intensity-modulated radiotherapy (IMRT) (Radiation)
Dose Level 2
Experimental
- 40 mg BKM120 will be administered orally daily for 45 days.
- Cisplatin: Starting Dose 35 mg/m2, given IV, weekly on days: (1, 8, 15, 22, 29, 36 and 43).
- Radiotherapy: All participants will receive daily radiotherapy with intensity-modulated radiotherapy (IMRT) for 7 weeks.
干预措施: BKM120 (Drug)
Dose Level 2
Experimental
- 40 mg BKM120 will be administered orally daily for 45 days.
- Cisplatin: Starting Dose 35 mg/m2, given IV, weekly on days: (1, 8, 15, 22, 29, 36 and 43).
- Radiotherapy: All participants will receive daily radiotherapy with intensity-modulated radiotherapy (IMRT) for 7 weeks.
干预措施: Cisplatin (Drug)
Dose Level 2
Experimental
- 40 mg BKM120 will be administered orally daily for 45 days.
- Cisplatin: Starting Dose 35 mg/m2, given IV, weekly on days: (1, 8, 15, 22, 29, 36 and 43).
- Radiotherapy: All participants will receive daily radiotherapy with intensity-modulated radiotherapy (IMRT) for 7 weeks.
干预措施: Intensity-modulated radiotherapy (IMRT) (Radiation)
结局指标
主要结局
Maximum Tolerated Dose of Cisplatin
时间窗: While on treatment, up to 66 days
The trial uses 3+3 design to determine maximum tolerated dose (MTD).
Maximum Tolerated Dose of BKM120
时间窗: While on treatment, up to 66 days
The trial uses 3+3 design to determine maximum tolerated dose (MTD).
次要结局
- 24 Month Overall Survival(Up to 24 months)
- Median Depression Score Change(From baseline to cycle 9, up to 66 days.)
- Best Overall Response(Measured at end of treatment, up to 66 days)
- Median Anxiety Score Change(From baseline to cycle 9, up to 66 days.)
- P13K Status by Response(Biopsies drawn up to 10 days from registration. Response measured at from baseline to cycle 9, up to 66 days.)
- Median Time to Progression(Up to 24 months (Progression is defined using RECIST v1.0 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions))
研究者
Glenn J. Hanna
Principal Investigator
Dana-Farber Cancer Institute
研究点 (1)
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