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

NCT05374252 | Unknown Phase 3

• 1 other identifier: E2021144
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Anal Canal Cancer Stage III; Anal Squamous Cell Carcinoma; Anal Canal Cancer; Anal Cancer

Keywords

Anal Squamous Cell Carcinoma; Radiochemotherapy; PD-1

Outcome Measures

Primary Outcomes (3)

• Progression free survival

  progression free survival

  from the end of treatment to 3 years after treatment

• Overall survival

  overall survival

  from the end of treatment to 3 years after treatment

• cCR rate

  cCR rate 6 months after treatment

  6 months after treatment

Secondary Outcomes (7)

• Acute toxicities

  from the start of treatment to 3 months after treatment

• cCR rate

  3 months after treatment

• The rate of late toxicity according to the RTOG/EORTC scale

  3 years

• Colostomy rate

  2 year

• Local recurrence rate

  from the end of treatment to 3 years after treatment

Study Arms (2)

Experimental Group

EXPERIMENTAL

Concurrent PD-1 antibody sintilimab combined with mytomicin C, 5-fluorouracil, and IMRT, followed by adjuvant sintilimab

Drug: PD-1 inhibitor

Control Group

ACTIVE COMPARATOR

Concurrent mytomicin C and 5-fluorouracil combined with IMRT

Radiation: concurrent chemoradiotherapy

Interventions

PD-1 inhibitor DRUG

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

Also known as: radiation, concurrent chemotherapy

Experimental Group

concurrent chemoradiotherapy RADIATION

Two cycles of concurrent mytomicin C and 5-fluorouracil combined with IMRT

Also known as: radiation, concurrent chemotherapy

Control Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histology identified anal canal squamous carcinoma,
• Aged 18 to 75,
• Clinical staging III, Eastern Cooperative Oncology Group 0-2 score,
• 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,
• No previous anal canal surgery or anal tumor resection (except for biopsy),
• No previous chemotherapy or pelvic radiotherapy history,
• 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,
• Adequate bone marrow, liver, and kidney function,
• Clinical complete response (cCR) (Chest, abdominal and pelvic enhanced CT or pelvic enhanced MRI or PET/CT),
• Non-pregnant or breast-feeding women,
• 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,
• No other serious disease leading to shortened survival.

You may not qualify if:

• Diagnosed as stage I-II and well differentiated squamous cell carcinoma,
• Distant metastasis,
• Received radiation therapy in abdominal or pelvic regions,
• Pregnant, lactating woman patient or fertile but lacks adequate contraceptives,
• Arrhythmia need anti-arrhythmia treatment (except β-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,
• Severe hypertension not well controlled by drugs,
• Active phase of chronic hepatitis B or hepatitis C (high copies of virus DNA),
• Patients with active tuberculosis (TB) are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year before screening,
• Other active clinical severe infection (NCI-CTCAE (version 4.0) ),
• Dyscrasia, organ dysfunction,
• Known or suspicious allergy to any research-related drugs,
• Epilepsy needs treatments (Steroid or anti-epilepsy therapy),
• Other malignant tumor history within 5 years,
• Drug abuse and medical, psychological, or social factors that may interfere with patients' participation in the study or affect the evaluation of the study,
• 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,

Sponsors & Collaborators

• Sixth Affiliated Hospital, Sun Yat-sen University: lead

Study Sites (1)

The Sixth Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510630, China

RECRUITING

Related 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. doi: 10.1200/JCO.1997.15.5.2040.

  PMID: 9164216 BACKGROUND

• 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 Intergroup RTOG 98-11 phase 3 trial. Int J Radiat Oncol Biol Phys. 2013 Nov 15;87(4):638-45. doi: 10.1016/j.ijrobp.2013.07.035. Epub 2013 Sep 10.

  PMID: 24035327 RESULT

• 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 without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2 x 2 factorial trial. Lancet Oncol. 2013 May;14(6):516-24. doi: 10.1016/S1470-2045(13)70086-X. Epub 2013 Apr 9.

  PMID: 23578724 RESULT

• 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 Group trials 87-04 and 98-11. J Clin Oncol. 2010 Dec 1;28(34):5061-6. doi: 10.1200/JCO.2010.29.1351. Epub 2010 Oct 18.

  PMID: 20956625 RESULT

• 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 pembrolizumab in patients with recurrent carcinoma of the anal canal. Ann Oncol. 2017 May 1;28(5):1036-1041. doi: 10.1093/annonc/mdx029.

  PMID: 28453692 RESULT

• 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/ccr3.2333. eCollection 2019 Sep.

  PMID: 31534737 RESULT

• 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. doi: 10.1007/BF02586980. No abstract available.

  PMID: 4830803 RESULT

• 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 Mar 30;102(7):1123-8. doi: 10.1038/sj.bjc.6605605. Epub 2010 Mar 16.

  PMID: 20354531 RESULT

• 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):1049-54.

  PMID: 8874455 RESULT

MeSH Terms

Conditions

Anal Canal Carcinoma; Anus Neoplasms

Interventions

Immune Checkpoint Inhibitors; Radiation; Chemoradiotherapy

Condition Hierarchy (Ancestors)

Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Physical Phenomena; Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Study Officials

• Xiang-bo Wan, PhD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiang-bo Wan, PhD

CONTACT

+86-13826017157; wanxbo@mail.sysu.edu.cn

Fang He, MD

CONTACT

+86-20-85655905; hefang23@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2022
• First Posted: May 16, 2022
• Study Start: May 7, 2022
• Primary Completion: May 31, 2025
• Study Completion: December 31, 2025
• Last Updated: May 16, 2022

Record last verified: 2022-05

Locations

CN (1)