Personalized Long-course Radiotherapy Plus Chemotherapy With or Without Immunotherapy for LARC: PALACE Study

NCT07020247 | Recruiting Phase 3

• 1 other identifier: PALACE
• Study Type: interventional
• Target: 184
• Locations: 1 country
• Sites: 1

Brief Summary

The study is a multicenter, randomized controlled, phase III clinical study, and the purpose of the study is to explore the complete response rate (CR, Defined as pathological complete response (pCR) + Clinical complete response (cCR) sustained for over one year) of patients with locally advanced rectal cancer(LARC) treated with personalized long-course radiotherapy plus chemotherapy with or without Serplulimab. A total of 184 patients were included in this study.

Conditions

Locally Advanced Rectal Cancer (LARC); Immunotherapy; Radiotherapy; Total Neoadjuvant Therapy; Anal Function Preservation

Outcome Measures

Primary Outcomes (1)

• Complete response rate

  Defined as the combination of pathological complete response (pCR) and clinical complete response (cCR) sustained for over one year.

  1 year

Secondary Outcomes (9)

• R0 resection rates

  1 year

• Disease free survival

  3 years

• Anus-preserving rate

  1 year

• Locoregional recurrence-free survival (LRFS) rates

  3 years

• Distant metastasis free survival

  3 years

Study Arms (2)

Total Neoadjuvant Chemoradiotherapy+Serplulimab

EXPERIMENTAL

The experimental group intervention consists of the following: 1. Induction Phase: Two cycles of CAPOX and serplulimab prior to radiotherapy. 2. Concurrent Chemoradiotherapy: Two cycles of CAPOX and serplulimab administered concurrently with radiotherapy. 3. Consolidation Phase: Two additional cycles of CAPOX and serplulimab, initiated 2-3 weeks after completing radiotherapy. Radiotherapy is delivered using intensity-modulated radiotherapy (IMRT/VMAT) at a dose of 50-50.4Gy/25-28f (1.8-2.0Gy/d, 5f/w). For patients in the experimental group who achieve partial remission (PR) or better during the induction phase, an additional local boost dose of 6Gy/3f (2.0Gy/d, 5f/w) is administered to the PGTV. Tumor response is assessed 3-4 weeks after completing consolidation chemotherapy. Based on the evaluation, a decision is made to proceed with either total mesorectal excision (TME) or a watchful waiting strategy.

Drug: Anti-PD-1 antibody drug named Serplulimab; Radiation: Radiotherapy; Drug: Chemotherapy

Total Neoadjuvant Chemoradiotherapy

ACTIVE COMPARATOR

The control group intervention consists of the following: 1. Induction Phase: Two cycles of CAPOX prior to radiotherapy. 2. Concurrent Chemoradiotherapy: Two cycles of CAPOX administered concurrently with radiotherapy. 3. Consolidation Phase: Two additional cycles of CAPOX, initiated 2-3 weeks after completing radiotherapy. Radiotherapy is delivered using intensity-modulated radiotherapy (IMRT/VMAT) at a dose of 50-50.4Gy/25-28f (1.8-2.0Gy/d, 5f/w). Tumor response is assessed 3-4 weeks after completing consolidation chemotherapy. Based on the evaluation, a decision is made to proceed with either total mesorectal excision (TME) or a watchful waiting strategy.

Radiation: Radiotherapy; Drug: Chemotherapy

Interventions

Anti-PD-1 antibody drug named Serplulimab DRUG

Serplulimab

Total Neoadjuvant Chemoradiotherapy+Serplulimab

Radiotherapy RADIATION

Radiotherapy is delivered using intensity-modulated radiotherapy (IMRT/VMAT) at a dose of 50-50.4Gy/ 25-28f(1.8-2.0Gy/d, 5f/w). For patients in the experimental group who achieve partial remission (PR) or better during the induction phase, an additional local boost dose of 6Gy/3f(2.0Gy/d, 5f/w) is administered to the PGTV.(No PGTV dose was given in the control group). For the treatment of lymph node metastasis in the lateral pelvic wall outside the mesorectal area: no additional dose is required when surgery is feasible, a sequential boost dose of 15Gy/3f is added when the lymph nodes are not surgically resectable.

Total Neoadjuvant Chemoradiotherapy; Total Neoadjuvant Chemoradiotherapy+Serplulimab

Chemotherapy DRUG

Capox

Total Neoadjuvant Chemoradiotherapy; Total Neoadjuvant Chemoradiotherapy+Serplulimab

Eligibility Criteria

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

You may qualify if:

• Age: ≥18 years old; sex is not limited.
• Patients with stage II/III rectal cancer staged under MRI or endoscopic ultrasonography and have at least one risk factor: cT4a and invasion of intestinal lumen for more than 1/2 week (measured by MRI)；cT4b(resectable)；cT3c-d with EMVI+ (upper middle rectum)；cN2；MRF+ (≤2mm)；lower rectal cancer is located on the anterior wall and tumor reaching T3 and occupying the intestinal cavity for more than 1/2 week; lower rectal cancer is mainly located on the lateral posterior wall need invading the intestinal wall (anal sphincter) ≥ 5mm； tumor of lower rectal cancer invades the external anal sphincter or levator ani muscle (stage 4) . \[According to the 8th edition of the 2018 AJCC Cancer Staging Manual and the 2008 ESMO Lower Segment Colorectal Cancer Staging Criteria\] . The preoperative T stage is referred to endoscopic ultrasonography or rectal MRI. The N stage is referred to abdominal CT. The M stage is referred to abdominal and thoracic CT. If symptoms occur, other appropriate imaging examinations are needed (cranial MRI or ECT) . Patients with contraindications to MRI can be interpreted with caution based on CT and endoluminal ultrasound staging. MDT should review the staging of all patients.
• The lower edge of lesion is less than 10cm from anal verge according to rigid sigmoidoscopy or rectal digital examination.
• No distant metastasis after a thorough examination .
• Pathological diagnosis of rectal adenocarcinoma,and Immunohistochemistry and/or genetic testing for MSS/pMMR;
• ECOG score: 0-1.
• Patients with primary rectal cancer who had not received surgery prior to surgery (except for palliative ileostomy or colostomy), radiotherapy, systemic chemotherapy or other anti-tumor therapy.
• The main organ function is normal, including the following characteristics:
• ①Blood routine examination: HB ≥9g/dL, WBC ≥ 3.5/4.0×109/L，NE≥ 1.5×109/L，PLT≥ 100×109/L
• ②Biochemical examination：Crea and BIL ≤ 1.0 upper normal limit（ULN），ALT and AST≤ 2.5 upper normal limit（ULN）, ALP≤2.5×UNL，Tbil≤1.5×UNL。
• Not allergic to 5-Fu or Platinum.
• The site of radiotherapy had not previously received radiation.
• If female and of childbearing potential, have a negative result on a pregnancy test performed a maximum of 7 days before initiation of study treatment. If female and of childbearing potential, or if male, agree to use adequate contraception (eg, abstinence, intrauterine device, oral contraceptive, or double-barrier method) based on the judgment of the investigator or a designated associate from the date on which the ICF (Informed Consent Form) is signed until 8 weeks after the last dose of study drug.
• Participants are volunteered to participate in this study, sign informed consent, good compliance, cooperation with follow-up.

You may not qualify if:

• Patients who have previously received pelvic radiotherapy.
• Presence of active or progressive infection requiring systemic treatment, such as active tuberculosis, active hepatitis, etc.
• Presence of systemic diseases that are not stably controlled by the investigator, including diabetes mellitus, hypertension, liver cirrhosis, rheumatic immune diseases, and severe lung diseases.
• Have had prior or concurrent cancer distinct in primary site or histology (including synchronous colon cancer) , except for curatively treated cervical cancer in situ, Basal cell carcinoma of skin.
• Has any other disease, metabolic abnormality, physical examination abnormality, or laboratory abnormality that, in the judgment of the investigator, has reason to suspect that the patient has a disease or condition for which the study drug is inappropriate for use, or that would affect the interpretation of the study results, or place the patient in a high-risk condition.
• Estimated inadequate patient compliance to participate in this clinical study.
• History of gastrointestinal fistula, perforation, bleeding or severe ulceration or presence of severe gastrointestinal disease that affects the absorption of oral chemotherapy drugs.
• Patients who have received solid organ transplantation or bone marrow transplantation, or have had active autoimmune disease requiring systemic therapy within 2 years prior to the first dose.

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (1)

West China Hospital

Chengdu, Sichuan, 610041, China

RECRUITING

MeSH Terms

Interventions

Radiotherapy; Drug Therapy

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Wang Xin

CONTACT

+86 28 85423609; wangxin213@sina.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 6, 2025
• First Posted: June 13, 2025
• Study Start: November 19, 2024
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): January 31, 2028
• Last Updated: June 13, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)