Clinical Phase II Trial Evaluating the Efficacy of Systemic Mesenchymal Stromal Cell (MSC) Injections for the Treatment of Severe and Chronic Radiotherapy-induced Abdomino-pelvic Complications (Pelvic Radiation Disease, PRD) Refractory to Standard Therapy
试验速览
- 阶段
- 2 期
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Decrease of one grade on the LENT SOMA
研究概览
简要总结
Patients receiving radiation therapy are still at risk for side effects due to off-target radiation damage of normal tissues The number of cancer patients is expected to increase from 14.1 million around the world in 2012 to 19.3 million in 2025. Up to ten percent will develop late severe gastrointestinal complications (i.e. Pelvic Radiation Disease - PRD). Symptoms are proctopathy (5-20%) and radiation-induced cystitis (3,5%) that affect quality of life. The treatment of PRD is limited to managing the symptoms; new alternatives should be proposed.
Clinical trials using MSCs to treat hemorrhagic cystitis, proctopathy have demonstrated the feasibility to used MSCs in these pathologies :
- MSCs successfully repair hemorrhagic cystitis, and perforated colon in patients with hemorrhagic cystitis, perforated colon and peritonitis.
- Six clinical trials are currently ongoing for proctopathy, 3 are phase III. Results suggest an inhibition of chronic inflammation and fistulization and interruption of hemorrhagic syndromes.
- Clinical trials to evaluate the efficacy of MSCs to treat hemorrhagic cystitis is in progress.
- A decrease in pain after the injection of MSCs was observed in patients treated by radiotherapy for breast cancer, radiation burns, and radiotherapy over-dosage.
- Four patients, were treated with MSCs after receiving overdose pelvic irradiation for prostate cancer. A decrease in pain (EN score), bleeding and diarrhea was observed.
MSCs will represent a promising alternative strategy in the treatment of severe enteritis, rectitis and cystitis after radiotherapy, and may avoid surgical treatment and may diminish the adverse effect of PRD in terms of chronicity, morbidity, mortality and health costs.
详细描述
-Chemo-radiation enhances survival but also increases the risk of PRD. The result will be an increasing
- Cost for society (repeated hospitalization for palliative care)
- An ethical problem to help these patients with irreversible degraded quality of life.
Results from conventional therapies for PRD reveal a poor long-term efficacy:
i. Coagulation by plasma argon is insufficient, 58% at 6 months; ii. The efficacy of formalin is questionable (48%), as is 5-amino-salicylate, sulfasalazine, vitamin E and pentoxifylline ; iii. The efficacy of short chain fatty acids and hyperbaric oxygen therapy is low (40%); iv. Steroids are of limited efficacy (37%). v. A surgical operation in an irradiated field is associated with difficult or impossible healing as well as with risks of infection (mortality of 5% within 40 months) Furthermore, conventional therapies are palliative and badly tolerated. More effective approaches are thus crucial.
- PRD unfortunately remains a major side effect of radiotherapy and there is no established effective treatment. Consequently, the recruitment of the aforementioned number of patients by participating radiotherapy centers is ensured.
- MSC therapy is a safe and suitable option in severe PRD.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age ≥18 years and <80 years;
- •Any pelvic cancerous pathology irradiated with a history of pelvic complications of grade > 2 LENT SOMA scale);
- •Absence of metastasis objectified by bone scintigraphy;
- •After failure following at least three lines of conventional treatment;
- •Good physical condition (WHO-performance status 0-1)
排除标准
- •Pregnancies (Pregnancy test carried out during the inclusion examination).
研究组 & 干预措施
Mesenchymal Stromal Cell (MSC)
Patient with chronic radiotherapy-induced abdomino-pelvic complications refractory to standard therapy: 12 patients suffering of PRD (LENT-SOMA scale>2)
干预措施: Mesenchymal Stromal Cell (MSC) injections (Drug)
结局指标
主要结局
Decrease of one grade on the LENT SOMA
时间窗: 4 months after the first injection of MSCs
Decrease of one grade for rectorrhagia or hematuria on the LENT SOMA scale (Late Effects Normal Tissue Task Force -Subjective, Objective, Management, Analytic), 4 months after the first injection of MSCs.
次要结局
- The effect of treatment on analgesic drug consumption (analgesic, opiates).(4 months after the first injection of MSCs)
- The effect of treatment on quality of life with SF36 questionnaire(4 months after the first injection of MSCs)
- The effect of treatment on quality of life with HADS questionnaire(4 months after the first injection of MSCs)
- The effect of treatment on pain(4 months after the first injection of MSCs)
- Frequency of diarrhea(4 months after the first injection of MSCs)