A Phase III ,Randomized controlled study comparing triple oral metronomic chemotherapy with low dose immunotherapy to intravenous chemotherapy in patients with advanced platinum sensitive head and neck squamous cell carcinoma in first line palliative setting.
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 422
- 试验地点
- 3
- 主要终点
- To assess if TMCI results in a non-inferior OS as compared to platinum-based combination chemotherapy in patients with advanced unresectable or metastatic HNSCC that is platinum-sensitive in the first line palliative setting
研究概览
简要总结
Objective:
To evaluate the efficacy of triple oral metronomic chemotherapy with low dose immunotherapy (TMCI) over standard intravenous (IV) platinum-based chemotherapy in advanced unresectable locally advanced or metastatic HNSCC in the palliative setting.
Information:
The combination of oral metronomic chemotherapy with low dose immunotherapy found to be superior to oral metronomic chemotherapy alone which has led to use of this treatment in routine care in the clinic. However, as this is not compared with IV chemotherapy with advanced HNSCC that is platinum-sensitive, would this replace platinum-based combination chemotherapy, even in cases in which cetuximab and pembrolizumab are unaffordable is always been question discussed and both are used routinely in this setting. Therefore the TMCI regimen is proven to be non-inferior or superior to standard IV platinum-based combination chemotherapy, this will provide patients with an easily accessible, available and affordable therapeutic option.In this study 422 participants will be included in either of the standard treatment arms in ratio 1:1 by process of randomization .Response will be assessed after every two – three months and the he response rate will be calculated as a percentage of patients having a complete response and partial response as the best response, which will be assessed in accordance with RECIST version 1.1 criteria. Duration of response will be defined as the duration in months from the first occurrence of response (complete response or partial response) until progression
**Interventions (I):**Patients allotted to the intervention arm will receive triple metronomic chemotherapy with low dose nivolumab (TMCI arm). TMC will consist of capsule celecoxib 200 mg twice daily, weekly methotrexate 9 mg/m2 once a week, and erlotinib 150 mg once daily, all administered orally. In addition, patients with receive intravenous nivolumab 20 mg administered in 100 mL normal saline over 60 minutes once every 3 weeks. A 21-day period will be considered a cycle.
Control group (C):
CP (cisplatin 75 mg/m2 day 1or Carboplatin (area under the curve [AUC], 6 and paclitaxel 175 mg/m2 over 3hours on day 1) will be administered every 3 weeks. Carboplatin (areaunder the curve [AUC], 6) will be substituted for cisplatin in case of development of grade 2 or greater neuropathyor renal impairment (creatinine clearance< 50 mL/min), or at physician’s or patient’s choice.
**Expected outcome:**If we are able to prove that TMCI is non-inferior or superior to standard IV chemotherapy, we will have established a low cost and easily accessible less toxic treatment regimen, which will benefit not just individual patients and families, but also society.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •1 Subjects must have head and neck squamous cell carcinoma and must be planned for palliative systemic therapy in the first line.
- •2 Patients who have received prior platinum chemotherapy in the definitive setting will be eligible as long as the disease has relapsed 6 months or beyond the time that they had received platinum therapy.
- •Age more than 18 years.
- •Eastern Cooperative Oncology Group ECOG performance status PS 0 2 3 Subjects must have normal organ and marrow function 4 Patients with HIV are potentially eligible as long as they have a CD4 count more than and equal to 200 are on concurrent HAART highly active antiretroviral therapy, and absence of active AIDS defining conditions.
- •5 Pregnancy test Negative serum or urine pregnancy test at screening for women of childbearing potential.
- •6 Contraception Highly effective contraception for both male and female subjects throughout the study and for at least 30 days after last nivolumab treatment administration if the risk of conception exists.
- •Nivolumab is teratogenic to the developing human fetus.Should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study, she should inform her treating physician immediately.
- •Willing and able to comply with all study requirements, including treatment, able to be followed up at regular intervals and or nature of required assessments.
- •7Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Subjects who are receiving any other current investigational agents.
- •IMMUNOSUPPRESSANTS Current use of immunosuppressive medication EXCEPT for the following a.
- •intranasal, inhaled, topical steroids, or local steroid injection b.
- •Systemic corticosteroids at physiologic doses more than and equal to 10 mg per day of prednisone or equivalent c.
- •Steroids as premedication for hypersensitivity reactions d.
- •Steroids for raised intracranial pressure due to the disease itself e, Steroid use for avoidance or treatment of emesis.
- •AUTOIMMUNE DISEASE Active autoimmune disease that might deteriorate when receiving a chemotherapeutic agent.
- •Patients with diabetes type I vitiligo psoriasis or hypo or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
- •ORGAN TRANSPLANTATION Prior organ transplantation including allogeneic stem cell transplantation.
- •VACCINATION Vaccination with live viral vaccine within 4 weeks of the first dose of nivolumab and while on studyis prohibited except for administration of inactivated vaccines.
- •HYPERSENSITIVITY TO STUDY DRUG Known prior severe hypersensitivity to platinum, paclitaxel, oral metronomic chemotherapy, or nivolumab or any component in their formulations, including known severehypersensitivity reactions to monoclonal antibodies
- •CARDIOVASCULAR DISEASE: Clinically significant cardiovascular disease cerebrovascular accident or stroke less than 6 months prior to enrollment myocardial infarction less than 6 months prior to enrollment, unstable angina, congestive heart failure, or serious cardiac arrhythmia requiring medication.
- •OTHER PERSISTING TOXICITIES Persisting toxicity related to prior therapy; however, alopecia, sensory neuropathy Grade 2, or other Grade 2 not constituting a safety risk based on Investigator’s judgment is acceptable.
- •Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
- •Pregnant women are excluded from this study.
- •Based on its mechanism of action.
- •nivolumab can cause foetal harm when administered to a pregnant woman.
- •Therefore, potential risks of administering nivolumab during pregnancy include increased rates of abortion or stillbirth.
- •Women of reproductive potential will be advised to use effective contraception during treatment and for at least one month after the last dose of nivolumab.
- •Lactating women There is no information regarding the presence of nivolumab in human milk, the effects on the breastfed infant, or the effects on milk production.
- •Since many drugs are excreted in human milk, it is advised that a lactating woman should not breastfeed during treatment and for at least one month after the last dose of nivolumab due to the potential for serious adverse reactions in breastfed infants.
结局指标
主要结局
To assess if TMCI results in a non-inferior OS as compared to platinum-based combination chemotherapy in patients with advanced unresectable or metastatic HNSCC that is platinum-sensitive in the first line palliative setting
时间窗: till 5 years
次要结局
- Secondary(1 To assess if TMCI leads to superior OS as compared to platinum-based combination chemotherapy in advanced unresectable or metastatic HNSCC that is platinum-sensitive in the first line palliative setting)
研究者
Dr Vanita Noronha
Tata Memorial centre