Chemotherapy plus PD-1 immunotherapy before surgery for locally advanced rectal cancer (CONTROL-01)

Neoadjuvant Chemotherapy and Tislelizumab (PD-1 Inhibitior) for Locally Advanced Rectal Cancer: a Single-center, Prospective, Phase II Study

This trial will try three cycles of CAPOX chemotherapy together with the PD-1 drug tislelizumab before surgery in adults with locally advanced rectal cancer to see if it is safe and helps improve tumor control.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: The Affiliated Hospital of Qingdao University (Academic / other)
• Drugs / interventions: Tislelizumab, chemotherapy
• Locations: 1 site (Qingdao, Shandong)
• Trial ID: NCT06647680 on ClinicalTrials.gov

What this trial studies

Participants receive three cycles (9 weeks) of CAPOX (oxaliplatin + capecitabine) combined with the PD-1 inhibitor tislelizumab as preoperative treatment, followed by a two-week rest and surgical resection with adjuvant therapy decided by postoperative pathology. Treatment may be modified or continued for patients who develop toxicity but still derive benefit, at the investigator's discretion. After stopping study treatment, safety follow-up occurs at about 30 and 90 days, then survival follow-up visits occur approximately every three months for a total follow-up of 36 months. Eligibility is confirmed by pathology, contrast-enhanced imaging, performance status, and routine laboratory tests.

Who should consider this trial

Good fit: Adults with pathologically confirmed rectal adenocarcinoma clinically staged T3–T4 N0–N2 M0, ECOG 0–1, adequate organ function, and willingness to receive preoperative CAPOX plus tislelizumab and undergo surgery are the intended participants.

Not a fit: Patients with distant metastases (M1), poor performance status, significant organ dysfunction, active second cancers, or those unwilling to have surgery or immunotherapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could increase the rate of complete tumor responses before surgery and reduce recurrence risk, potentially improving long-term outcomes.

How similar studies have performed: Some neoadjuvant immunotherapy combinations have shown promising complete response rates—especially in mismatch repair–deficient rectal cancers—while preoperative CAPOX plus tislelizumab in locally advanced, predominantly mismatch repair–proficient disease is a relatively novel approach.

Eligibility criteria

Inclusion Criteria:

* Be willing and able to provide written informed consent for the trial
* Age 18 years or greater
* Pathologically proven diagnosis of adenocarcinoma of the rectum
* Clinically determined to be stage T3 or T4, N0-N2, and M0
* Be fully active, able to carry on all pre-disease performance without restriction or Restricted in physically strenuous activity.
* Contrast-enhanced imaging of the abdomen and chest by CT to exclude distant metastases and provide local tumor stage
* Preoperative ECOG status score 0-1
* Preoperative ASA grade I-III
* Adequate bone marrow function
* Adequate renal and liver function
* No active second cancers
* Be willing and able to comply with all aspects of the protocol
* Women of childbearing potential must have used reliable contraception or have had a pregnancy test result within 7 days prior to enrollment. Be negative and willing to use an adequate method of contraception for the duration of the trial and for 8 weeks after the last administration of the trial drug.
* Adequate bone marrow function defined as follows: Absolute neutrophil count (ANC) ≥ 1,200 cells/mm3 Platelets ≥ 100,000 cells/mm3 Hemoglobin ≥ 8.0 g/dl.
* Adequate hepatic function within within 28 days before registration on this study:total bilirubin must be ≤ ULN (upper limit of normal) for the lab unless the patient has a bilirubin elevation \> ULN to 1.5 x ULN due to Gilbert\'s disease or similar syndrome involving slow conjugation of bilirubin; and AST and ALT must be ≤3 x ULN for the lab If AST and/or ALT is ≥ ULN but ≤ 3 x ULN, serologic testing for Hepatitis B and C must be performed and results for viral infection must be negative.
* Adequate renal function within 28 days before randomization defined as serum creatinine ≤ 1.5 x ULN for the lab or calculated creatinine clearance \> 30 mL/min

Exclusion Criteria:

* Age less than 18 years
* Pregnant or breastfeeding women
* Prior invasive malignancy unless disease free for a minimum of three years
* Preoperative body temperature ≥ 38°C or concurrent infectious diseases requiring systemic therapy;
* Severe mental illness;
* Severe abnormal heart, lung and kidney function
* History of unstable angina pectoris or myocardial infarction within 6 months;
* History of cerebral infarction or cerebral hemorrhage within 6 months;
* Patients with abnormal coagulation function;
* Have a history of psychotropic drug abuse or have a mental disorder;
* Continuous use of glucocorticoids within 1 month (except topical application);
* Patient has participated in or is participating in other clinical studies (within 6 months);
* According to the judgment of the investigator, it endangers the patient\'s health or affects the experimental results.

Where this trial is running

Qingdao, Shandong

• The affiliated hospital of Qingdao university — Qingdao, Shandong, China (Recruiting)

Study contacts

• Study coordinator: Yun Lu

Conditions Rectal Cancer Patients; Rectal cancer; Chemotherapy; Tislelizumab; Complete response; Recurrence free survival