Clinical trial NCT04680195: Thalidomide in the Treatment of Chronic Radiation Proctitis With Intractable Bleeding
Official title: Prospective, Open Clinical Trial of Thalidomide in the Treatment of Chronic Radiation Proctitis With Intractable Bleeding
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Chronic Radiation Proctitis
Keywords: Thalidomide
Bleeding
Chronic radiation proctitis
Lead sponsor: Sixth Affiliated Hospital, Sun Yat-sen University
Sponsor class: OTHER
First posted: 2020-12-22
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Thalidomide Group
Primary purpose: TREATMENT

Brief summary: Chronic radiation proctitis (CRP) is the main secondary toxic injury after pelvic radiotherapy. Hematochezia is the most common symptom for more than 80% of CRP patients.

Non-surgical treatment is the first choice to the treatment of CRP to avoid the occurrence of serious complications. Conventional oral medication for the treatment of bleeding CRP is very few and has little effect. At present, no oral medication has been found to significantly alleviate and control refractory bleeding of CRP. Therefore, it is an urgent problem to screen out a drug that is more effective, safe and highly compliant for the treatment of hemorrhagic CRP.

Thalidomide has anti-inflammatory, immune regulation, anti-angiogenesis and other effects. For the patients of CRP with intractable bleeding, a prospective, open clinical trial will be carried out to observe the safety and effectiveness of thalidomide in treating hemorrhagic CRP.

Detailed description: Radiotherapy is an essential therapeutic tool for pelvic malignancies such as uterine cervix, uterine corpus, prostate, testicular, urinary bladder and rectal cancers. According to reports, the estimated number of new cases of malignant pelvic tumors in China in 2015 alone exceeded 500,000. Chronic radiation proctitis (CRP) is an unavoidable and commonly observed side effect, occurs 3 months later and in 5-20% of patients after pelvic malignancy radiation. Hematochezia is the most common symptom for more than 80% of CRP patients, which is a persistent, irreversible and progressive symptom, and will probably give rise to anemia. In clinic, the treatment for intractable bleeding of CRP is very difficult.

Non-surgical treatment is the first choice to the treatment of CRP to avoid the occurrence of serious complications. Conventional oral medication for the treatment of bleeding CRP is very few and has little effect. At present, no oral medication has been found to significantly alleviate and control refractory bleeding of CRP. Therefore, it is an urgent problem to screen out a drug that is more effective, safe and highly compliant for the treatment of hemorrhagic CRP.

Thalidomide has anti-inflammatory, immune regulation, anti-angiogenesis and other effects. A large number of studies have shown that thalidomide can be used to treat Crohn's disease, ulcerative colitis, radiation cystitis, etc., and it can treat moderate to severe of IBD patients can inhibit inflammatory response, improve clinical symptoms, promote intestinal mucosal repair. Further, recent studies have proved that thalidomide can be used to treat intestinal bleeding due to vascular dysplasia. And a case report from Gut described that refractory bleeding of CRP of a 78-year-old woman were significantly alleviated after taking thalidomide.

Therefore, for the patients of CRP with intractable bleeding, a prospective, open clinical trial planed to carry out to observe the safety and effectiveness of thalidomide in treating hemorrhagic CRP.

Eligibility criteria: Inclusion criteria

1. Patients aged 18-75 years;
2. Patients with ECOG physical condition score of 0-2;
3. Patients with previous pathological diagnosis of pelvic tumors (Gynecology, prostate, urinary system);
4. Patients with a history of pelvic radiotherapy, at least 6 months from the end of the last radiotherapy;
5. Patients with no primary tumor recurrence or metastasis;
6. Patients with refractory hemorrhagic CRP who have failed to conventional treatment (SOMA score for hematochezia≥2, hemoglobin level ≤90g/L, or a history of blood transfusion due to CRP)
7. Subjects and their family members can understand the research plan, and are willing to participate, and sign an informed consent form.

Exclusion Criteria:

1. Patients with active bleeding requiring emergency treatment;
2. Patients with severe complications of CRP, such as Rectal ulcer (VRS\>Grade 3) or fistula, perforation, stenosis, necrosis, perianal intractable pain and so on
3. Patients with a history of rectal resection;
4. Other bleeding diseases, such as grade III or IV hemorrhoids, coagulation dysfunction, etc.;
5. Patients with other diseases requiring long-term use of anticoagulant drugs;
6. Combined intestinal obstruction, requiring surgery;
7. The absolute value of neutrophils of patients is lower than 750/mm3;
8. Patients who are allergic to thalidomide;
9. Pregnant or lactating women;
10. Patients with severe mental illness;
11. Patients who cannot take medication or follow up as planned;
12. During the trial and within 3 months after the trial, the subjects and their partners are not willing to contraception;
13. Participants in other clinical investigators 3 months before the trial

Primary outcomes:
measure: Remission rate of rectal bleeding one month after thalidomide treatment
timeFrame: the first month after thalidomide treatment
Secondary outcomes:
measure: Remission rate of rectal bleeding one month during thalidomide treatment
timeFrame: the first month during thalidomide treatment
measure: Remission rate of rectal bleeding two months during thalidomide treatment
timeFrame: the second month during thalidomide treatment
measure: Remission rate of rectal bleeding three months during thalidomide treatment
timeFrame: the third month during thalidomide treatment
measure: Remission rate of rectal bleeding four months during thalidomide treatment
timeFrame: the fourth month during thalidomide treatment
measure: Remission rate of rectal bleeding three months after thalidomide treatment
timeFrame: the third month after thalidomide treatment
measure: Remission rate of rectal bleeding six months after thalidomide treatment
timeFrame: the sixth month after thalidomide treatment
measure: Endoscopic score one month during thalidomide treatment
timeFrame: the first month during thalidomide treatment
measure: Endoscopic score four months during thalidomide treatment
timeFrame: the fourth month during thalidomide treatment
measure: Endoscopic score one month after thalidomide treatment
timeFrame: the first month after thalidomide treatment
measure: Endoscopic score three months after thalidomide treatment
timeFrame: the third month after thalidomide treatment
measure: Endoscopic score six months after thalidomide treatment
timeFrame: the sixth month after thalidomide treatment
measure: Quality of life of the patient one month during thalidomide treatment
timeFrame: the first month during thalidomide treatment
measure: Quality of life of the patient two months during thalidomide treatment
timeFrame: the second month during thalidomide treatment
measure: Quality of life of the patient three months during thalidomide treatment
timeFrame: the third month during thalidomide treatment
measure: Quality of life of the patient four months during thalidomide treatment
timeFrame: the fourth month during thalidomide treatment
measure: Quality of life of the patient one month after thalidomide treatment
timeFrame: the first month after thalidomide treatment
measure: Quality of life of the patient three months after thalidomide treatment
timeFrame: the third month after thalidomide treatment
measure: Quality of life of the patient six months after thalidomide treatment
timeFrame: the sixth month after thalidomide treatment
measure: Incidence of adverse events four months during thalidomide treatment
timeFrame: the fourth month during thalidomide treatment
measure: Incidence of adverse events six months after thalidomide treatment
timeFrame: the sixth month after thalidomide treatment
Other outcomes:
Locations:
Study officials:
References:
citation: Yuan ZX, Ma TH, Zhong QH, Wang HM, Yu XH, Qin QY, Chu LL, Wang L, Wang JP. Novel and Effective Almagate Enema for Hemorrhagic Chronic Radiation Proctitis and Risk Factors for Fistula Development. Asian Pac J Cancer Prev. 2016;17(2):631-8. doi: 10.7314/apjcp.2016.17.2.631.
citation: Andreyev HJ. Argon plasma coagulation in chronic radiation proctitis: Postgate et al. Endoscopy. 2007 Aug;39(8):751-2; author reply 752. doi: 10.1055/s-2007-966772. No abstract available.
citation: Craanen ME, van Triest B, Verheijen RH, Mulder CJ. Thalidomide in refractory haemorrhagic radiation induced proctitis. Gut. 2006 Sep;55(9):1371-2. doi: 10.1136/gut.2006.099416. No abstract available.
citation: Zhou S, Wang F, Hsieh TC, Wu JM, Wu E. Thalidomide-a notorious sedative to a wonder anticancer drug. Curr Med Chem. 2013;20(33):4102-8. doi: 10.2174/09298673113209990198.
citation: Yuan ZX, Ma TH, Wang HM, Zhong QH, Yu XH, Qin QY, Wang JP, Wang L. Colostomy is a simple and effective procedure for severe chronic radiation proctitis. World J Gastroenterol. 2016 Jun 28;22(24):5598-608. doi: 10.3748/wjg.v22.i24.5598.
citation: Kim KT, Chae HS, Kim JS, Kim HK, Cho YS, Choi W, Choi KY, Rho SY, Kang SJ. Thalidomide effect in endothelial cell of acute radiation proctitis. World J Gastroenterol. 2008 Aug 14;14(30):4779-83. doi: 10.3748/wjg.14.4779.
citation: Bauditz J, Wedel S, Lochs H. Thalidomide reduces tumour necrosis factor alpha and interleukin 12 production in patients with chronic active Crohn's disease. Gut. 2002 Feb;50(2):196-200. doi: 10.1136/gut.50.2.196.
citation: Alberto SF, Felix J, de Deus J. Thalidomide for the treatment of severe intestinal bleeding. Endoscopy. 2008 Sep;40(9):788; author reply 789. doi: 10.1055/s-2008-1077513. Epub 2008 Sep 4. No abstract available.
citation: Bauditz J, Schachschal G, Wedel S, Lochs H. Thalidomide for treatment of severe intestinal bleeding. Gut. 2004 Apr;53(4):609-12. doi: 10.1136/gut.2003.029710.
citation: McCrone LF, Neary PM, Larkin J, McCormick P, Mehigan B. The surgical management of radiation proctopathy. Int J Colorectal Dis. 2017 Aug;32(8):1099-1108. doi: 10.1007/s00384-017-2803-y. Epub 2017 Apr 20.
citation: Ma TH, Yuan ZX, Zhong QH, Wang HM, Qin QY, Chen XX, Wang JP, Wang L. Formalin irrigation for hemorrhagic chronic radiation proctitis. World J Gastroenterol. 2015 Mar 28;21(12):3593-8. doi: 10.3748/wjg.v21.i12.3593.