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临床试验/NCT03389477
NCT03389477
进行中（未招募）
2 期

Los Tres Paso Trial: Step One - Neoadjuvant Palbociclib Monotherapy, Step Two - Concurrent Chemoradiation Therapy, and Step Three - Adjuvant Palbociclib Monotherapy in Patients With p16INK4a Negative, HPV-Unrelated Head and Neck Squamous Cell Carcinoma

Washington University School of Medicine2 个研究点 分布在 1 个国家目标入组 26 人开始时间: 2018年4月27日最近更新:
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适应症Head and Neck Squamous Cell Carcinoma
干预措施Intensity-Modulated Radiation TherapyPeripheral blood drawTumor biopsyPalbociclibCisplatinCetuximab
相关药物PalbociclibCetuximabCisplatin

概览

阶段
2 期
状态
进行中（未招募）
入组人数
26
试验地点
2
主要终点
Tumor Response Rate of Newly Diagnosed p16INK4a Negative, HPV-unrelated HNSCC to Neoadjuvant Palbociclib Monotherapy
概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

概览

简要总结

The purpose of this study is to evaluate the results of treating patients with HPV-unrelated head and neck squamous cell carcinoma with neoadjuvant single-agent palbociclib, followed by chemoradiation (either cisplatin + IMRT or cetuximab + IMRT depending on patient characteristics), followed by adjuvant single-agent palbociclib.

研究设计

研究类型
Interventional
分配方式
Non Randomized
干预模型
Parallel
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

  • •Larynx SCC, hypopharynx SCC, or oral cavity SCC. HPV-unrelated OPSCC \[defined as p16INK4a negative by IHC (staining in \< 70% of cells) or HPV High Risk (Type 16 or 18) negative by ISH\]. P16INK4a positive larynx SCC, hypopharynx SCC, and oral cavity SCC are eligible given the unknown effect of this on the biology of SCC of these subsites.
  • •Overall Stage III, IVA, or IVB disease per AJCC version 7.0
  • •Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
  • •At least 18 years of age.
  • •Normal bone marrow function as defined below:
  • •Absolute neutrophil count ≥ 1,000/mcL
  • •Platelets ≥ 100,000/mcL
  • •Hemoglobin ≥ 9.0 g/dL
  • •QTc \< 500 msec by Fridericia
  • •Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 90 days after completion of treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.

排除标准

  • •Diagnosis of cutaneous, paranasal sinus, salivary, or nasopharynx SCC, or diagnosis of neck nodes with unknown primary.
  • •Diagnosis of P16/HPV-ISH positive OPSCC.
  • •Presence of distant metastatic disease.
  • •Prior systemic therapy for current diagnosis of HNSCC.
  • •A history of other malignancy ≤ 2 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or low risk/curatively treated prostate, thyroid, and cervical cancers.
  • •Currently receiving any other investigational agents.
  • •Treated within the last 7 days prior to Day 1 of protocol therapy with:
  • •Food or drugs that are known to be STRONG CYP3A4 inhibitors (e.g. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, telithromycin, indinavir, ritonavir, nelfinavir, atazanavir, amprenavir, nefazodone, diltiazem, and delavirdine) or inducers (e.g. glucocorticoids, progesterone, rifampin, phenobarbital, St. John's wort) \[moderate CYP3A4 inhibitors/inducers are okay\]
  • •Drugs that are known to prolong the QT interval
  • •Drugs that are proton pump inhibitors

研究组 & 干预措施

Cohort 1: 1: palbociclib, 2: Cisplatin & IMRT, 3: palbociclib

Experimental
  • Step 1: Neoadjuvant palbociclib monotherapy (125 mg/day, Days 1-21 of a 28-day cycle for two cycles)
  • Step 2: Cisplatin 100 mg/m^2 given on Days 1 and 22 with accelerated IMRT 70 Gy to be administered over 6 weeks
  • Step 3: Adjuvant palbociclib 125 mg/day, days 1-21 of each 28-day cycle for six cycles. Adjuvant palbociclib will begin 16 to 22 weeks following completion of cisplatin & IMRT

干预措施: Intensity-Modulated Radiation Therapy (Radiation)

Cohort 1: 1: palbociclib, 2: Cisplatin & IMRT, 3: palbociclib

Experimental
  • Step 1: Neoadjuvant palbociclib monotherapy (125 mg/day, Days 1-21 of a 28-day cycle for two cycles)
  • Step 2: Cisplatin 100 mg/m^2 given on Days 1 and 22 with accelerated IMRT 70 Gy to be administered over 6 weeks
  • Step 3: Adjuvant palbociclib 125 mg/day, days 1-21 of each 28-day cycle for six cycles. Adjuvant palbociclib will begin 16 to 22 weeks following completion of cisplatin & IMRT

干预措施: Peripheral blood draw (Procedure)

Cohort 2: 1: palbociclib, 2: Cetuximab & IMRT, 3: palbociclib

Experimental
  • Step 1: Neoadjuvant palbociclib monotherapy (125 mg/day, Days 1-21 of a 28-day cycle for two cycles)
  • Step 2: Cetuximab given one week before RT and then weekly with accelerated IMRT 70 Gy to be administered over 6 weeks
  • Step 3: Adjuvant palbociclib 125 mg/day, days 1-21 of each 28-day cycle for six cycles. Adjuvant palbociclib will begin 16 to 22 weeks following completion of cetuximab & IMRT

干预措施: Peripheral blood draw (Procedure)

Cohort 1: 1: palbociclib, 2: Cisplatin & IMRT, 3: palbociclib

Experimental
  • Step 1: Neoadjuvant palbociclib monotherapy (125 mg/day, Days 1-21 of a 28-day cycle for two cycles)
  • Step 2: Cisplatin 100 mg/m^2 given on Days 1 and 22 with accelerated IMRT 70 Gy to be administered over 6 weeks
  • Step 3: Adjuvant palbociclib 125 mg/day, days 1-21 of each 28-day cycle for six cycles. Adjuvant palbociclib will begin 16 to 22 weeks following completion of cisplatin & IMRT

干预措施: Tumor biopsy (Procedure)

Cohort 2: 1: palbociclib, 2: Cetuximab & IMRT, 3: palbociclib

Experimental
  • Step 1: Neoadjuvant palbociclib monotherapy (125 mg/day, Days 1-21 of a 28-day cycle for two cycles)
  • Step 2: Cetuximab given one week before RT and then weekly with accelerated IMRT 70 Gy to be administered over 6 weeks
  • Step 3: Adjuvant palbociclib 125 mg/day, days 1-21 of each 28-day cycle for six cycles. Adjuvant palbociclib will begin 16 to 22 weeks following completion of cetuximab & IMRT

干预措施: Intensity-Modulated Radiation Therapy (Radiation)

Cohort 2: 1: palbociclib, 2: Cetuximab & IMRT, 3: palbociclib

Experimental
  • Step 1: Neoadjuvant palbociclib monotherapy (125 mg/day, Days 1-21 of a 28-day cycle for two cycles)
  • Step 2: Cetuximab given one week before RT and then weekly with accelerated IMRT 70 Gy to be administered over 6 weeks
  • Step 3: Adjuvant palbociclib 125 mg/day, days 1-21 of each 28-day cycle for six cycles. Adjuvant palbociclib will begin 16 to 22 weeks following completion of cetuximab & IMRT

干预措施: Tumor biopsy (Procedure)

Cohort 1: 1: palbociclib, 2: Cisplatin & IMRT, 3: palbociclib

Experimental
  • Step 1: Neoadjuvant palbociclib monotherapy (125 mg/day, Days 1-21 of a 28-day cycle for two cycles)
  • Step 2: Cisplatin 100 mg/m^2 given on Days 1 and 22 with accelerated IMRT 70 Gy to be administered over 6 weeks
  • Step 3: Adjuvant palbociclib 125 mg/day, days 1-21 of each 28-day cycle for six cycles. Adjuvant palbociclib will begin 16 to 22 weeks following completion of cisplatin & IMRT

干预措施: Palbociclib (Drug)

Cohort 1: 1: palbociclib, 2: Cisplatin & IMRT, 3: palbociclib

Experimental
  • Step 1: Neoadjuvant palbociclib monotherapy (125 mg/day, Days 1-21 of a 28-day cycle for two cycles)
  • Step 2: Cisplatin 100 mg/m^2 given on Days 1 and 22 with accelerated IMRT 70 Gy to be administered over 6 weeks
  • Step 3: Adjuvant palbociclib 125 mg/day, days 1-21 of each 28-day cycle for six cycles. Adjuvant palbociclib will begin 16 to 22 weeks following completion of cisplatin & IMRT

干预措施: Cisplatin (Drug)

Cohort 2: 1: palbociclib, 2: Cetuximab & IMRT, 3: palbociclib

Experimental
  • Step 1: Neoadjuvant palbociclib monotherapy (125 mg/day, Days 1-21 of a 28-day cycle for two cycles)
  • Step 2: Cetuximab given one week before RT and then weekly with accelerated IMRT 70 Gy to be administered over 6 weeks
  • Step 3: Adjuvant palbociclib 125 mg/day, days 1-21 of each 28-day cycle for six cycles. Adjuvant palbociclib will begin 16 to 22 weeks following completion of cetuximab & IMRT

干预措施: Palbociclib (Drug)

Cohort 2: 1: palbociclib, 2: Cetuximab & IMRT, 3: palbociclib

Experimental
  • Step 1: Neoadjuvant palbociclib monotherapy (125 mg/day, Days 1-21 of a 28-day cycle for two cycles)
  • Step 2: Cetuximab given one week before RT and then weekly with accelerated IMRT 70 Gy to be administered over 6 weeks
  • Step 3: Adjuvant palbociclib 125 mg/day, days 1-21 of each 28-day cycle for six cycles. Adjuvant palbociclib will begin 16 to 22 weeks following completion of cetuximab & IMRT

干预措施: Cetuximab (Drug)

结局指标

主要结局

Tumor Response Rate of Newly Diagnosed p16INK4a Negative, HPV-unrelated HNSCC to Neoadjuvant Palbociclib Monotherapy

时间窗: 2 cycles (56 days)

* Tumor response rate is defined as the proportion of subjects who achieve a complete response (CR) or partial response (PR) based on RECIST criteria * CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). * PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

次要结局

  • Combined Local-regional Disease Relapse Risk and Distant Metastases Risk Following Completion of CRT(Through 18 months after completion of step 2)
  • Median Progression-free Survival (PFS) (Stratified by Cohort) of Patients Treated With the Three Step Sequence of Palbociclib Monotherapy, CRT, and Adjuvant Palbociclib Monotherapy(Through 5 years after completion of step 2)
  • Progression-free Survival (PFS) of Patients Treated With the Three Step Sequence of Palbociclib Monotherapy, CRT, and Adjuvant Palbociclib Monotherapy(Through 2 years after completion of step 2)
  • Median Overall Survival (OS) of Patients Treated With the Three Step Sequence of Palbociclib Monotherapy, CRT, and Adjuvant Palbociclib Monotherapy(Through 5 years after completion of step 2)
  • Overall Survival of Patients Treated With the Three Step Sequence of Palbociclib Monotherapy, CRT, and Adjuvant Palbociclib Monotherapy(Through 2 years after completion of step 2)
  • Change in Genomic Alterations in Tumor Tissue(At baseline and at time of disease relapse (up to 5 years))
  • Association Between Baseline Tumor CDKN2A and CCND1 Alterations and Tumor Response to Palbociclib Given Before CRT and Relapse After CRT(At baseline and at time of disease relapse (up to 5 years))

研究者

申办方类型
Other
责任方
Sponsor

研究点 (2)

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