Phase 2 Study of Pemetrexed in Combination With Cisplatin and Cetuximab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
The purpose of this trial is to estimate progression free survival in patients with recurrent or metastatic head and neck cancer that have not received chemotherapy in this setting.
详细描述
A 12 patient safety lead will evaluate side effects in patients receiving at least 2 cycles of the combination pemetrexed, cisplatin and cetuximab.
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
- •Histologically confirmed diagnosis of squamous cell carcinoma of head and neck (SCCHN)
- •Recurrent or metastatic SCCHN, not amenable to local therapy
- •At least 6 months since completion of systemic therapy (chemotherapy or biological anticancer therapy)
- •No more than 1 prior systemic therapy, given as part of multimodal treatment for locally advanced disease;
- •No prior systemic therapy for metastatic disease
- •Radiation therapy must be completed at least 4 weeks before study enrollment.
- •For palliative therapy, prior radiation therapy allowed to <25% of the bone marrow (Cristy and Eckerman 1987), and prior radiation to the whole pelvis is not allowed.
- •Surgery (excluding prior diagnostic biopsy) must be completed at least 4 weeks before study enrollment.
- •An estimated life expectancy of at least 12 weeks.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Oken et al. 1982).
- •Biological tissue available for biomarker analysis on tumor tissue.
- •Disease status may be measurable or nonmeasurable as defined by Response Evaluation Criteria in Solid Tumors
- •Patient compliance and geographic proximity that allow for adequate follow-up.
- •Adequate organ function
- •Willingness to comply with Contraceptive Regimen
- •For women: Must be surgically sterile, postmenopausal, or compliant with a medically approved contraceptive regimen [for example, intrauterine device (IUD), birth control pills, or barrier device] during and for 6 months after the treatment period; must have a negative serum or urine pregnancy test within 7 days before study enrollment, and must not be breast-feeding. For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 6 months after the treatment period.
排除标准
- •Nasopharyngeal, paranasal sinus, lip, or salivary gland cancer.
- •Previously received treatment with monoclonal antibody therapy, or other signal transduction inhibitors of Epidermal Growth Factor Receptor therapy.
- •Are receiving concurrent chronic systemic immune therapy, or chemotherapy for a disease other than cancer.
- •Serious concomitant systemic disorder (for example, active infection) or psychiatric disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study.
- •Have serious cardiac disease, such as symptomatic , unstable angina, or the history of myocardial infarction in the previous 12 months.
- •Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
- •Have had another primary malignancy other than Head and Neck cancer, unless that prior malignancy was treated at least 2 years previously with no evidence of recurrence. Exception: Patients with a history of in situ carcinoma of the cervix, nonmelanoma skin cancer, or low-grade (Gleason score less than or equal to 6) localized prostate cancer will be eligible even if diagnosed and treated less than 2 years previously.
- •Presence of clinically significant (by physical exam) third-space fluid collections; for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study entry.
- •Have peripheral neuropathy
- •Have central nervous system (CNS) metastases (unless the patient has completed successful local therapy for CNS metastases and has been off corticosteroids for at least 4 weeks before starting study therapy). Brain imaging is required in symptomatic patients to rule out brain metastases, but is not required in asymptomatic patients.
- •Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents, other than an aspirin dose less than or equal to 1.3 grams per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam).
- •Unable or unwilling to take folic acid, vitamin B12, or prophylactic corticosteroids.
- •Recent (within 30 days before enrollment) or concurrent yellow fever vaccination.
- •Pregnant or breast-feeding
研究组 & 干预措施
Pemetrexed + Cisplatin + Cetuximab
Participants will receive pemetrexed,cisplatin and cetuximab for up to 6 cycles (21 days per cycle) followed by optional maintenance of pemetrexed and cetuximab until disease progression. Optional maintenance therapy is permitted after at least 4 cycles of triplet combination therapy have been given. Cetuximab will be administered as an initial dose of 400 milligram per meter squared (mg/m^2) intravenous (IV) infusion and as a 250 mg/m^2 IV weekly dose thereafter.
As Standard of care dietary supplements included: 350 to 1000 micrograms (µg) oral Folic Acid 5 times a day for the 7 days preceding the first dose of first dose of pemetrexed and continuing throughout treatment and for 21 days after the last dose of pemetrexed and 1000 µg vitamin B12 intramuscular injection (IM) during the week preceding the first dose of pemetrexed and every 9 weeks thereafter.
干预措施: Pemetrexed (Drug)
Pemetrexed + Cisplatin + Cetuximab
Participants will receive pemetrexed,cisplatin and cetuximab for up to 6 cycles (21 days per cycle) followed by optional maintenance of pemetrexed and cetuximab until disease progression. Optional maintenance therapy is permitted after at least 4 cycles of triplet combination therapy have been given. Cetuximab will be administered as an initial dose of 400 milligram per meter squared (mg/m^2) intravenous (IV) infusion and as a 250 mg/m^2 IV weekly dose thereafter.
As Standard of care dietary supplements included: 350 to 1000 micrograms (µg) oral Folic Acid 5 times a day for the 7 days preceding the first dose of first dose of pemetrexed and continuing throughout treatment and for 21 days after the last dose of pemetrexed and 1000 µg vitamin B12 intramuscular injection (IM) during the week preceding the first dose of pemetrexed and every 9 weeks thereafter.
干预措施: Cetuximab (Drug)
Pemetrexed + Cisplatin + Cetuximab
Participants will receive pemetrexed,cisplatin and cetuximab for up to 6 cycles (21 days per cycle) followed by optional maintenance of pemetrexed and cetuximab until disease progression. Optional maintenance therapy is permitted after at least 4 cycles of triplet combination therapy have been given. Cetuximab will be administered as an initial dose of 400 milligram per meter squared (mg/m^2) intravenous (IV) infusion and as a 250 mg/m^2 IV weekly dose thereafter.
As Standard of care dietary supplements included: 350 to 1000 micrograms (µg) oral Folic Acid 5 times a day for the 7 days preceding the first dose of first dose of pemetrexed and continuing throughout treatment and for 21 days after the last dose of pemetrexed and 1000 µg vitamin B12 intramuscular injection (IM) during the week preceding the first dose of pemetrexed and every 9 weeks thereafter.
干预措施: Cisplatin (Drug)
Pemetrexed + Cisplatin + Cetuximab
Participants will receive pemetrexed,cisplatin and cetuximab for up to 6 cycles (21 days per cycle) followed by optional maintenance of pemetrexed and cetuximab until disease progression. Optional maintenance therapy is permitted after at least 4 cycles of triplet combination therapy have been given. Cetuximab will be administered as an initial dose of 400 milligram per meter squared (mg/m^2) intravenous (IV) infusion and as a 250 mg/m^2 IV weekly dose thereafter.
As Standard of care dietary supplements included: 350 to 1000 micrograms (µg) oral Folic Acid 5 times a day for the 7 days preceding the first dose of first dose of pemetrexed and continuing throughout treatment and for 21 days after the last dose of pemetrexed and 1000 µg vitamin B12 intramuscular injection (IM) during the week preceding the first dose of pemetrexed and every 9 weeks thereafter.
干预措施: Folic Acid (Dietary Supplement)
Pemetrexed + Cisplatin + Cetuximab
Participants will receive pemetrexed,cisplatin and cetuximab for up to 6 cycles (21 days per cycle) followed by optional maintenance of pemetrexed and cetuximab until disease progression. Optional maintenance therapy is permitted after at least 4 cycles of triplet combination therapy have been given. Cetuximab will be administered as an initial dose of 400 milligram per meter squared (mg/m^2) intravenous (IV) infusion and as a 250 mg/m^2 IV weekly dose thereafter.
As Standard of care dietary supplements included: 350 to 1000 micrograms (µg) oral Folic Acid 5 times a day for the 7 days preceding the first dose of first dose of pemetrexed and continuing throughout treatment and for 21 days after the last dose of pemetrexed and 1000 µg vitamin B12 intramuscular injection (IM) during the week preceding the first dose of pemetrexed and every 9 weeks thereafter.
干预措施: Vitamin B12 (Dietary Supplement)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Baseline to date of PD or death up to 18.7 months
PFS based on Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines defined as the time from the date of first dose of study drug to first documented objective progressive disease (PD) or death from any cause. PD is defined as at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
次要结局
- Overall Survival (OS)(Baseline to date of death up to 18.7 months)
- Change From Baseline in Participant Reported European-Quality of Life 5 Dimension Instrument (EQ-5D) Visual Analog Scale (VAS) at End of Triplet Combination Therapy and End of Maintenance Therapy(Baseline, End of Triplet Combination Therapy (up to Cycle 6 [4.2 months]), End of Maintenance Therapy (up to 18.7 months))
- Change From Baseline in Participant Reported EQ-5D Utility Score at End of Triplet Combination Therapy and End of Maintenance Therapy(Baseline, End of Triplet Combination Therapy (up to 6 cycles [4.2 months]) , End of Maintenance Therapy (up to 18.7 months))
- Percent of Participants With a Partial Response (PR) or a Complete Response (CR)(Date of first response to PD (up to 18.7 months))
- Change From Baseline in Performance Status Scale for Head and Neck Cancer Patients (PSS-HNC)(Baseline, Triplet Combination Therapy Cycles 2, 4, 6 (cycle = 21 days) and optional Maintenance Therapy Cycles 1, 3, 5 and 7 (cycle = 21 days))