Randomized Multicenter Clinical Trial of Early Integration of Palliative Care With Chemoradiotherapy Versus Chemoradiotherapy Alone in Patients With Locally Advanced Unresectable Head and Neck Cancer.
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- ESAS-R score #1 (cross comparison)
研究概览
简要总结
In Portugal, approximately 2,424 new cases of head and neck cancer are diagnosed each year, of which 60% are already at an advanced stage, presenting with intense pain and dysphagia (difficulty swallowing). There is also marked social isolation due to communication difficulties, economic hardship, and facial disfigurement (altered facial appearance). As a result, patients frequently face challenges in accessing specialised palliative care services, encountering delays, fragmentation, or a complete absence of such care.
The i-CARE-HN study is the solution: investigators aim to integrate outpatient palliative care with oncological treatment -namely chemoradiotherapy -at an earlier stage of the disease-when it is still limited to the throat and neck region, without metastasis (spread to other organs). This means multidisciplinary support from the outset of oncological treatment - symptom control, psychological support, and quality of life - without delaying the cure. It is like giving the patient a 'shield' against suffering, enabling them to complete treatment more efficiently.
In the i-CARE-HN study, early palliative care aims to better manage patients' symptoms (such as pain, difficulty speaking, swallowing, breathing, dry mouth, loss of appetite, and anxiety), to clarify doubts, to support therapeutic decisions, and to strengthen communication between the patient and the team, without replacing the primary oncological treatment. Rather than waiting for symptoms to worsen before seeking help, this support will be provided throughout treatment with chemotherapy and radiotherapy. Through this simultaneous integration of outpatient palliative care into oncological treatment, investigators hope to improve patients' symptoms and quality of life, as well as clinical outcomes: fewer treatment interruptions, improved treatment tolerability, fewer emergency hospitalisations, and greater overall survival. Investigators will want to know how patients are feeling throughout the process, and to that end, will invite them to complete a survey at several points during the study. Responses to the questionnaires are critical to enabling the medical team to rapidly identify which participating patients present with the most significant symptoms and the greatest risk of complications.
This study plans to recruit 64 patients aged 18 years or older, with a recent diagnosis of locally advanced, inoperable cancer, being followed on an outpatient basis at the IPO de Coimbra, IPO do Porto, and ULS de Coimbra, who will be invited to participate in the study. Should the patient agree to participate, some baseline data will be collected, and patients will subsequently be randomly assigned to one of two groups: one group will receive isolated chemoradiotherapy (standard treatment: cisplatin 100 mg/m² every 3 weeks- days 1, 22, and 49- and daily radiotherapy 70 Gy in 35 fractions over 7 weeks) and the other group will receive chemoradiotherapy alongside palliative care, on an outpatient basis (access to palliative care consultations). Patients randomised to the standard treatment group (chemoradiotherapy without a structured early palliative care intervention) will not have palliative care appointments systematically scheduled. However, should a referral to palliative care be requested, the patient may be directed to that clinical department.
详细描述
Each year, more than 890,000 people worldwide receive a diagnosis of head and neck cancer. These patients face a devastating symptom burden: pain, difficulty swallowing, airway obstruction, speech loss, and disfigurement profoundly disrupt eating, communication, and social participation. At the time of diagnosis, patients with advanced head and neck cancer have a markedly reduced health-related quality of life, with global quality of life and emotional functioning approximately 50% lower than expected, compared with patients with other solid tumours. Treatment with surgery, radiotherapy, and chemotherapy often intensifies these symptoms during active therapy. Many patients experience persistent dry mouth, swallowing dysfunction, and taste changes that extend well beyond the first year. The physical morbidity of advanced head and neck cancer is associated with significant psychological distress, social isolation, and an increased risk of suicide compared with other cancer types. Despite this substantial burden, access to specialised palliative care services remains lower than the estimated need.
Given the aggressive biology of head and neck cancer and a palliative phase that may be shorter than six months, timely integration of oncology and specialised palliative care remains a clinical priority. In advanced cancers broadly, a systematic review and meta-analysis of 43 randomised trials found that early palliative care improved quality of life by approximately 11 points on a 0-184 scale and reduced overall symptom burden by approximately 10 points on a 0-90 scale at one to three months, with no effect on survival. The landmark trial by Temel et al. in patients with metastatic non-small-cell lung cancer demonstrated that early palliative care alongside standard oncological treatment improved quality of life, reduced depressive symptoms, and was associated with longer median survival. A subsequent large randomised trial further supported the benefit of early integrated palliative care on symptom burden and patient-reported outcomes in advanced cancer. Critically, however, none of these trials was designed for or reported outcomes specific to head and neck cancer. The only head and neck cancer-specific phase III randomised trial, by Patil et al. (n=180), found no significant improvement in quality of life or survival at 12 weeks, possibly reflecting the brevity of the intervention and high baseline supportive care intensity. Pilot and non-randomised studies suggest feasibility and potential benefit but remain underpowered. Ratnasekera et al. (2023) published the only scoping review protocol mapping palliative care interventions in head and neck cancer.
The lack of HNC-specific evidence limits the ability of multidisciplinary HNC teams to make evidence-based decisions regarding the integration of palliative care services. Clinical practice guidelines from organisations such as the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO), and the Portuguese Ministry of Health recommend early palliative care for patients with advanced cancer, based largely on evidence from lung cancer and other solid tumours, with limited head and neck cancer (HNC)-specific guidance.
Establishing the effectiveness of integrated palliative care specifically in advanced HNC is essential to inform clinical practice, resource allocation, and future research priorities in this vulnerable population. Thus, the investigators hypothesise that the early integration of palliative care with standard oncological treatment will improve symptom burden and quality of life in patients with advanced head and neck cancer.
To evaluate the impact of early palliative care integration alongside chemoradiotherapy in patients with unresectable locally advanced head and neck cancer, on patient-reported outcomes and health resource utilisation. The study aims to determine whether palliative care, introduced at the outset of CRT, improves symptom burden, quality of life, treatment adherence, serum stress levels, inflammatory markers, and health resource utilisation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Single (Outcomes Assessor)
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
- •Each patient must fulfil all of the following criteria:
- •Diagnosis of locally advanced (unresectable) head and neck squamous cell carcinoma (HNSCC) of the oral cavity, oropharynx, larynx, and hypopharynx, staged according to the TNM AJCC 8th edition, proposed at a multidisciplinary team (MDT) meeting for definitive chemoradiotherapy (CRT) on an outpatient basis;
- •Age ≥18 years;
- •ECOG performance status 0-2;
- •Adequate organ function: haemoglobin ≥9 g/dL; neutrophils ≥1.5×10⁹/L; platelets ≥100×10⁹/L; creatinine ≤1.5×ULN; bilirubin, AST, ALT, LDH ≤1.5×ULN;
- •Signed informed consent by the participant.
排除标准
- •Each patient will be excluded if they meet any of the following criteria:
- •ECOG performance status 3-4;
- •Previous follow-up by specialised palliative care;
- •Primary tumours of the nasopharynx, oesophagus, lip, or salivary glands;
- •Metastatic head and neck cancer (oral cavity, oropharynx, larynx, and hypopharynx);
- •Severe comorbidities: decompensated cardiovascular disease (NYHA class III/IV heart failure, recent myocardial infarction), severe COPD (FEV₁ <50% predicted), renal insufficiency (eGFR <30 mL/min), hepatic insufficiency (Child-Pugh B/C);
- •Laboratory values: neutrophils <1.5×10⁹/L, platelets <100×10⁹/L, haemoglobin <9 g/dL, creatinine >1.5×ULN;
- •Diagnosis of dementia;
- •Participation in another clinical trial.
结局指标
主要结局
ESAS-R score #1 (cross comparison)
时间窗: 12 weeks after inclusion in the study
Patient-reported evaluation of 9 relevant symptoms (pain, fatigue, somnolence, nausea, loss of appetite, dyspnea, depression, anxiety and well-being) and an open section for reporting "other problems", using a scale from 0 (no symptom) to 10 (maximum intensity symptom) for every symptom. The final score is obtained by summing all symptom evaluations (ranging from 0-100). Aim: To determine the impact of early integration of outpatient palliative care alongside chemoradiotherapy on the symptom burden of patients. It will be assessed in both study groups (control and intervention). Note: ESAS-R tool includes a final body diagram allowing participants to indicate the location of pain.
次要结局
- ESAS-R score #2 (cross/longitudinal comparison)(12 weeks after inclusion in the study)
- Hospitalisation occurrence Type 1 (CTC-AE =>3)(It will comprise 5 compulsory timepoints: (1)CRT-day 1, (2)CRT-day 22, (3)CRT-day 49, (4)up to 7 weeks- end of CRT, (5)12 weeks post-inclusion; and two optional timepoints: (1)6 months after inclusion and (2)12 months after inclusion.)
- Hospitalisation occurrence Type 2 (CTC-AE =>3)(It will comprise 5 compulsory timepoints: (1)CRT-day 1, (2)CRT-day 22, (3)CRT-day 49, (4)up to 7 weeks- end of CRT, (5)12 weeks post-inclusion; and two optional timepoints: (1)6 months after inclusion and (2)12 months after inclusion.)
- Hospitalisation occurrence Type 3 (CTC-AE =>3)(It will comprise 5 compulsory timepoints: (1)CRT-day 1, (2)CRT-day 22, (3)CRT-day 49, (4)up to 7 weeks- end of CRT, (5)12 weeks post-inclusion; and two optional timepoints: (1)6 months after inclusion and (2)12 months after inclusion.)
- Hospitalisation occurrence Type 4 (CTC-AE =>3)(It will comprise 5 compulsory timepoints: (1)CRT-day 1, (2)CRT-day 22, (3)CRT-day 49, (4)up to 7 weeks- end of CRT, (5)12 weeks post-inclusion; and two optional timepoints: (1)6 months after inclusion and (2)12 months after inclusion.)
- Adherence to treatment (qualitative) see compliance(Four timepoints during CRT treatment period: (1)CRT-day 1, (2)CRT-day 22, (3)CRT-day 49 and (4)up to 7 weeks- end of CRT.)
- Opioid prescription (qualitative)(Four timepoints during CRT treatment period: (1)CRT-day 1, (2)CRT-day 22, (3)CRT-day 49 and (4)up to 7 weeks- end of CRT.)
- Overall Survival (OS)(12 months after inclusion in the study)
- EORTC QLQ-C30 v3.0 score (Quality of Life PROM)(It will comprise 5 timepoints: (1)Baseline, (2)CRT-day 1, (3)up to 7 weeks- end of CRT, (4)12 weeks post-inclusion, (5)12 months after inclusion.)
- Eastern Cooperative Oncology Group (ECOG) Performance Status scale(It will comprise 8 timepoints: (1)Baseline, (2)CRT-day 1, (3)CRT-day 22, (4)CRT-day 49, (5)up to 7 weeks- end of CRT, (6)12 weeks post-inclusion, (7)6 months after inclusion and (8)12 months after inclusion.)
- Palliative Care Complexity Assessment Tool (IDC-Pal) Score(It will comprise 2 compulsory timepoints: (1)CRT-day 1 and (2)12 weeks post-inclusion; and other 5 optional timepoints: (1)CRT-day 22, (2)CRT-day 49, (3)up to 7 weeks- end of CRT, (4)6 months post-inclusion and (5)12 months post-inclusion.)
- C-reactive Protein (PCR)- mg/dL(It comprises 6 compulsory timepoints: (1)Screening (before CRT); (2)CRT-day 1, (3)CRT-day 22, (4)CRT-day 49, (5)up to 7 weeks-end of CRT, (6)12 weeks post-inclusion; and 2 optional timepoints: (1)6 months post-inclusion and (2)12 months post-inclusion.)
- Procalcitonin (PCT)- ng/mL(It comprises 6 compulsory timepoints: (1)Screening (before CRT); (2)CRT-day 1, (3)CRT-day 22, (4)CRT-day 49, (5)up to 7 weeks-end of CRT, (6)12 weeks post-inclusion; and two optional timepoints: (1)6 months post-inclusion and (2)12 months post-inclusion.)
- Cortisol (nmol/L)(It comprises 6 compulsory timepoints: (1)Screening (before CRT); (2)CRT-day 1, (3)CRT-day 22, (4)CRT-day 49, (5)up to 7 weeks-end of CRT, (6)12 weeks post-inclusion; and two optional timepoints: (1)6 months post-inclusion and (2)12 months post-inclusion.)
研究者
Maria Margarida Paiva Cardoso Teixeira Pimparel
Oncologist
Portuguese Oncology Institute, Coimbra