Chemoradiotherapy Combined With or Without PD-1 Blockade in Anal Canal Squamous Carcinoma Patients

Anal Cancer Clinical Trial

Official title:

A Phase 3, Multicenter, Double-Blind Randomized Study of Mitomycin, 5-Fluorouracil and IMRT Combined With or Without Anti-PD-1 in Patients With Locally Advanced Anal Canal Squamous Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05374252
• Other study ID #: E2021144
• Status: Recruiting
• Phase: Phase 3
• Start date: May 7, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2022
• Source: Sixth Affiliated Hospital, Sun Yat-sen University
• Contact: Xiang-bo Wan, PhD
• Phone: +86-13826017157
• Email: wanxbo[@]mail.sysu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase III, multi-center, double-blind randomized controlled trial assessing the efficacy and safety of concurrent mitomycin C/5-Fu chemotherapy and long-course IMRT combined with PD-1 antibody Sintilimab for locally advanced anal canal squamous carcinoma patients, by comparing an experiment group (traditional chemoradiotherapy with PD-1 antibody Sintilimab) with a control group (traditional treatment without Sintilimab).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 102
• Est. completion date: December 31, 2025
• Est. primary completion date: May 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Histology identified anal canal squamous carcinoma,

2. Aged 18 to 75,

3. Clinical staging III, Eastern Cooperative Oncology Group 0-2 score,

4. The Staging method: All patients undergoing rectal anus palpation, high resolution MRI and chest-abdominal enhanced CT, clinical data should be re-evaluated and inclusive by center evaluation group when there is contradictory staging, distant metastasis were excluded by chest-abdominal enhanced CT and pelvic enhanced MRI,

5. No previous anal canal surgery or anal tumor resection (except for biopsy),

6. No previous chemotherapy or pelvic radiotherapy history,

7. No biopharmaceutical treatment history (such as monoclonal antibody), immunotherapy (such as anti PD-1antibody, anti PD-L1 antibody, anti PD-L2 antibody or anti CTLA-4), or other research drug treatment in the previous 5 years,

8. Adequate bone marrow, liver, and kidney function,

9. Clinical complete response (cCR) (Chest, abdominal and pelvic enhanced CT or pelvic enhanced MRI or PET/CT),

10. Informed consent assigned, Final inclusion criteria,

11. Non-pregnant or breast-feeding women,

12. No other malignant disease within 5 years before diagnosis of anal cancer squamous carcinoma (except endocervical cancer in situ or skin basal cell carcinoma which had been cured); no other malignant disease beside anal cancer squamous carcinoma,

13. No other serious disease leading to shortened survival.

Exclusion Criteria:

1. Diagnosed as stage I-II and well differentiated squamous cell carcinoma,

2. Distant metastasis,

3. Received radiation therapy in abdominal or pelvic regions,

4. Pregnant, lactating woman patient or fertile but lacks adequate contraceptives,

5. Arrhythmia need anti-arrhythmia treatment (except ß-blocking agent or Digoxin), symptomatic coronary heart disease or myocardial ischemia (myocardial infarction within 6 months) or congestive heart-failure (CHF) > New York Heart Association grade II,

6. Severe hypertension not well controlled by drugs,

7. Active phase of chronic hepatitis B or hepatitis C (high copies of virus DNA),

8. Patients with active tuberculosis (TB) are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year before screening,

9. Other active clinical severe infection (NCI-CTCAE (version 4.0) ),

10. Dyscrasia, organ dysfunction,

11. Known or suspicious allergy to any research-related drugs,

12. Epilepsy needs treatments (Steroid or anti-epilepsy therapy),

13. Other malignant tumor history within 5 years,

14. Drug abuse and medical, psychological, or social factors that may interfere with patients' participation in the study or affect the evaluation of the study,

15. Patients have any active autoimmune diseases or a history of autoimmune diseases (including but not restricted: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism and decreased thyroid function; patients with vitiligo or with complete remission of asthma in childhood and without any intervention in adulthood may be included; patients with asthma requiring bronchodilators intervention are not included,

16. Any anti-infection vaccine 4 weeks before inclusion,

17. Long-term exposure to immune-suppressor, combination of systemic or topical use of corticosteroids (dose>10mg/day prednisolone or equivalent hormone),

18. Any unstable state might endanger the patients' safety and compliance,

19. Refuses to sign informed consent.

Related Conditions & MeSH terms

• Anal Canal Cancer
• Anal Cancer
• Anal Squamous Cell Carcinoma
• Anus Neoplasms
• Carcinoma
• Carcinoma, Squamous Cell

Intervention

Drug:
• PD-1 inhibitor
Two cycles of concurrent PD-1 antibody sintilimab combined with mytomicin C, 5-fluorouracil and IMRT, followed by adjuvant sintilimab for six months

Radiation:
• concurrent chemoradiotherapy
Two cycles of concurrent mytomicin C and 5-fluorouracil combined with IMRT

Locations

Country	Name	City	State
China	The Sixth Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sixth Affiliated Hospital, Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (9)

Bartelink H, Roelofsen F, Eschwege F, Rougier P, Bosset JF, Gonzalez DG, Peiffert D, van Glabbeke M, Pierart M. Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups. J Clin Oncol. 1997 May;15(5):2040-9. — View Citation

Ben-Josef E, Moughan J, Ajani JA, Flam M, Gunderson L, Pollock J, Myerson R, Anne R, Rosenthal SA, Willett C. Impact of overall treatment time on survival and local control in patients with anal cancer: a pooled data analysis of Radiation Therapy Oncology — View Citation

Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. UKCCCR Anal Cancer Trial Working Party. UK Co-ordinating Committee on Cancer Research. Lancet. 1996 Oct 19;348(9034) — View Citation

Gunderson LL, Moughan J, Ajani JA, Pedersen JE, Winter KA, Benson AB 3rd, Thomas CR Jr, Mayer RJ, Haddock MG, Rich TA, Willett CG. Anal carcinoma: impact of TN category of disease on survival, disease relapse, and colostomy failure in US Gastrointestinal — View Citation

James RD, Glynne-Jones R, Meadows HM, Cunningham D, Myint AS, Saunders MP, Maughan T, McDonald A, Essapen S, Leslie M, Falk S, Wilson C, Gollins S, Begum R, Ledermann J, Kadalayil L, Sebag-Montefiore D. Mitomycin or cisplatin chemoradiation with or withou — View Citation

Nigro ND, Vaitkevicius VK, Considine B Jr. Combined therapy for cancer of the anal canal: a preliminary report. Dis Colon Rectum. 1974 May-Jun;17(3):354-6. — View Citation

Northover J, Glynne-Jones R, Sebag-Montefiore D, James R, Meadows H, Wan S, Jitlal M, Ledermann J. Chemoradiation for the treatment of epidermoid anal cancer: 13-year follow-up of the first randomised UKCCCR Anal Cancer Trial (ACT I). Br J Cancer. 2010 Ma — View Citation

Ott PA, Piha-Paul SA, Munster P, Pishvaian MJ, van Brummelen EMJ, Cohen RB, Gomez-Roca C, Ejadi S, Stein M, Chan E, Simonelli M, Morosky A, Saraf S, Emancipator K, Koshiji M, Bennouna J. Safety and antitumor activity of the anti-PD-1 antibody pembrolizuma — View Citation

Shahjehan F, Kamatham S, Ritter A, Kasi PM. Dramatic response to modified docetaxel, cisplatin, and fluorouracil chemotherapy after immunotherapy in a patient with refractory metastatic anal cancer. Clin Case Rep. 2019 Aug 6;7(9):1729-1734. doi: 10.1002/c — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival	progression free survival	from the end of treatment to 3 years after treatment
Primary	Overall survival	overall survival	from the end of treatment to 3 years after treatment
Primary	cCR rate	cCR rate 6 months after treatment	6 months after treatment
Secondary	Acute toxicities	acute toxicities according to the NCI CTCAE (version 4.0)	from the start of treatment to 3 months after treatment
Secondary	cCR rate	cCR rate 3 months after treatment	3 months after treatment
Secondary	The rate of late toxicity according to the RTOG/EORTC scale	The rate of late toxicity according to the RTOG/EORTC scale	3 years
Secondary	Colostomy rate	colostomy rate	2 year
Secondary	Local recurrence rate	local recurrence rate	from the end of treatment to 3 years after treatment
Secondary	Distant metastasis rate	distant metastasis rate	from the end of treatment to 3 years after treatment
Secondary	Incidence rate of Grade =3 PD-1monoclonal antibody-related adverse events	Incidence rate of Grade =3 PD-1monoclonal antibody-related adverse events	1 year