Clinical trial NCT05420584: Neoadjuvant Arterial Embolization Chemotherapy Combined PD-1 Inhibitor for Locally Advanced Rectal Cancer
Official title: Phase Ⅱ Clinical Trial of Neoadjuvant Arterial Embolization Chemotherapy Combined Immune Checkpoint Inhibitor for Locally Advanced Rectal Cancer: A Single Arm Prospective Sturdy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Rectal Neoplasms
Lead sponsor: The Fourth Affiliated Hospital of Zhejiang University School of Medicine
Sponsor class: OTHER
Collaborators: name: Second Affiliated Hospital, School of Medicine, Zhejiang University
First posted: 2022-06-15
Enrollment: 83
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
Primary purpose: TREATMENT

Brief summary: Rectal cancer is one of the common malignant tumors of the digestive tract. Some patients with rectal cancer are already advanced tumors when they are first diagnosed. At this time, the tumor has local infiltration, the probability of recurrence and metastasis after surgical resection is high, and even radical tumor resection cannot be performed. Neoadjuvant chemotherapy and radiotherapy have become one of the important treatment methods for these patients to increase the rate of radical tumor resection. However, a series of side effects of neoadjuvant radiotherapy can even continue after the end of radiotherapy, and even increase the incidence of postoperative complications. Superselective arterial interventional chemotherapy has been widely used in preoperative neoadjuvant chemotherapy for various tumors, and its efficacy in rectal cancer has also been confirmed. In addition, as a hot spot in tumor treatment, tumor immunotherapy has shown exciting effects in the NICHE study of neoadjuvant immunotherapy before colon cancer surgery. Moreover, Oxaliplatin is a classic chemotherapeutic drug that induces Immunogenic cell death effects, which induce antitumor immunity.

Therefore, in order to optimize the preoperative neoadjuvant therapy plan, the investigators propose a treatment method of superselective arterial chemoembolization combined with immunotherapy and systemic chemotherapy, in order to obtain better preoperative conversion therapy effect and reduce the adverse reactions of neoadjuvant therapy.


Eligibility criteria: Inclusion Criteria:

1. Pathologically confirmed rectal adenocarcinoma (immunohistochemistry, polymerase chain reaction(PCR) or next-generation sequencing(NGS) sequencing methods are acceptable).
2. Magnetic resonance imaging (MRI) measurement of tumor inferior margin ≤12cm from the anus.
3. MRI staging is cT3-4 N0 or cT1-4 N+, no multiple primary cancers or distant metastasis.
4. Life expectancy ≥ 1 year.
5. No anti-tumor therapy, no contraindications to interventional embolization, immunotherapy and chemotherapy.
6. Patients who understand the study protocol and are willing to participate in this study provide written informed consent.

Exclusion Criteria:

1. Refuse to participate in this study.
2. Multifocal colorectal cancer.
3. Past history of malignancy, excluding basal cell carcinoma/papillary thyroid carcinoma/various types of carcinoma in situ.
4. Inability to receive chemotherapy, such as but not limited to bone marrow suppression, etc.
5. Major organ diseases (such as but not limited to chronic obstructive pulmonary disease, coronary heart disease and renal insufficiency, etc.) during acute exacerbation and or severe acute infectious diseases (such as but not limited to hepatitis, pneumonia and myocarditis, etc.), American Society of Anesthesiologists(ASA) score \> 3.
6. Mental disability or illiteracy or language and communication barriers cannot understand the research protocol.
7. There are contraindications to arterial puncture, such as but not limited to severe arteriosclerosis or even atresia, coagulation dysfunction, long-term use of anticoagulants and cannot be stopped, etc.
8. Obstruction or high risk of obstruction by rectal tumor and/or bleeding and/or perforation.
9. Peripheral sensory nerve disorder, unable to receive oxaliplatin-based chemotherapy.
10. Lateral pelvic lymph node metastasis (mainly supplied by the internal iliac artery).
11. Pregnancy or breastfeeding.
12. Contraindications for MRI。
13. Consecutive use of corticosteroids for more than 3 days within 1 month before signing the consent form。
14. MRI assessment was T4b or MRF positive。
15. Other scenarios deemed inappropriate by the investigators for this study.

Primary outcomes:
measure: Imaging Tumor Regression Rate
timeFrame: From date of the start of drugs treatment until the end of drugs treatment (nearly 3 weeks)
Secondary outcomes:
measure: Pathologic Complete Response
timeFrame: From date of the start of drugs treatment until the operation is completed (nearly 4 weeks)
measure: Disease Free Survival
timeFrame: 36 months
measure: Safety (The side effects)
timeFrame: 36 months
measure: Pathological Tumor Regression Rate
timeFrame: From date of the start of drugs treatment until the end of drugs treatment (nearly 3 weeks)
Other outcomes:
Locations:
city: Yiwu
country: China
facility: The Fourth Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
Study officials:
References:
citation: Patel UB, Taylor F, Blomqvist L, George C, Evans H, Tekkis P, Quirke P, Sebag-Montefiore D, Moran B, Heald R, Guthrie A, Bees N, Swift I, Pennert K, Brown G. Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience. J Clin Oncol. 2011 Oct 1;29(28):3753-60. doi: 10.1200/JCO.2011.34.9068. Epub 2011 Aug 29.
citation: Chalabi M, Fanchi LF, Dijkstra KK, Van den Berg JG, Aalbers AG, Sikorska K, Lopez-Yurda M, Grootscholten C, Beets GL, Snaebjornsson P, Maas M, Mertz M, Veninga V, Bounova G, Broeks A, Beets-Tan RG, de Wijkerslooth TR, van Lent AU, Marsman HA, Nuijten E, Kok NF, Kuiper M, Verbeek WH, Kok M, Van Leerdam ME, Schumacher TN, Voest EE, Haanen JB. Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers. Nat Med. 2020 Apr;26(4):566-576. doi: 10.1038/s41591-020-0805-8. Epub 2020 Apr 6.