Clinical trial NCT06246344: Adaptive Boost Radiotherapy to Primary Lesions and Positive Nodes in the Neoadjuvant Treatment of Locally Advanced Rectal Cancer
Official title: Efficacy and Safety of Adaptive Boost Radiotherapy to Primary Lesions and Positive Nodes in the Neoadjuvant Treatment of Locally Advanced Rectal Cancer: a Prospective, Randomized, Controlled, Phase III Trial
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Rectal Cancer
Keywords: neoadjuvant
rectal cancer
chemoradiotherapy
Lead sponsor: Shandong Cancer Hospital and Institute
Sponsor class: OTHER
First posted: 2024-02-07
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: locally advanced rectal cancer

Brief summary: This is a multicenter, randomized, controlled phase III trial to evaluate the efficacy and safety of adaptive boost radiotherapy to the primary lesions and positive lymph nodes based on MR or CBCT or FBCT-guided adaptive radiotherapy in the neoadjuvant treatment of locally advanced rectal cancer.

Detailed description: Locally advanced rectal cancer (LARC), typically stage II (cT3-4/N0) or stage III (cT1-4/N1-3), requires multimodal treatment. Surgical resection alone is associated with a high rate of local recurrence. Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME), on the other hand, can better control local recurrence in LARC patients. However, the overall pathological complete response (pCR) rate and clinical complete response (cCR) rate are still low, and there is an inconsistency between them, Therefore, the preservation of the anus is still a challenge. Optimizing neoadjuvant treatment strategies, including strategies such as increasing concurrent chemotherapy and increasing the dose of radiotherapy, is essential to improve tumor regression and anal preservation.

Radiotherapy is an important treatment for controlling local recurrence and downstaging LARC. A common cause of cancer recurrence in rectal cancer is that tumor cells metastasise nearby positive lymph nodes, such as the lateral pelvic lymph nodes These sites can serve as refuges where the cancer can regroup and either recur at the original site or spread to other areas. Various studies have also investigated the role of radiotherapy dose escalation in promoting tumor regression. Seldom have these studies examined dose escalation to both the primary lesions and positive lymph nodes. One of the major limiting factors is the tradeoff between destruction of the cancer itself and collateral damage to the neighboring healthy tissues. However, recent advances in the field have made great strides in overcoming this obstacle. Adaptive radiation therapy (ART), including magnetic resonance (MR)-guided, cone beam computed tomography (CBCT)-guided, and fan beam computed tomography (FBCT)-guided, allows direct imaging of the target and organs at risk (OAR), combined with optimization of the treatment plan for anatomical changes, to deliver high-quality dose escalation regimens to improve treatment response while protecting OAR such as the bladder, femoral heads, and small bowel.

We hypothesize that by implementing simultaneous integrated boost (SIB) or sequential boost (SB) radiotherapy to both the primary lesions and positive lymph nodes based on ART, we can improve the cCR and pCR rates without increasing surgical difficulty, while maintaining tolerable safety.

Against the above background, this study aims to conduct a multicenter, randomized, controlled phase III trial to evaluate the efficacy and safety of SIB or SB radiotherapy to the primary lesions and positive lymph nodes based on MR or CBCT or FBCT-guided ART in the neoadjuvant treatment of LARC. Eligible patients will be randomized 1:1 into experimental and control groups, both of which will undergo long course concurrent chemoradiotherapy (LCCRT), consolidation chemotherapy and TME surgery. During LCCRT, the experimental group will receive SIB or SB dose escalation based on MR or CBCT or FBCT-guided ART, while the control group will receive conventional dose without ART.

Eligibility criteria: Inclusion Criteria:

* Histopathologically confirmed rectal adenocarcinoma.
* Tumor located ≤10cm from the anal verge.
* Age ≥18 years.
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1.
* Primary treatment-naive tumor confirmed by endorectal ultrasound (ERUS) or -
* Magnetic resonance imaging (MRI) as cT3-4/N+ according to the 8th edition of AJCC staging.
* Ability to provide tissue and blood samples for translational research.
* Anticipated survival of ≥6 months.
* Normal major organ function (within 14 days prior to enrollment) and suitability for receiving chemoradiotherapy.

Exclusion Criteria:

* History of prior chemotherapy, radiotherapy, or surgical treatment for rectal cancer, including transanal tumor resection.
* Locally recurrent rectal cancer.
* History of familial adenomatous polyposis.
* Active Crohn's disease or ulcerative colitis.
* Allergy or hypersensitivity history to 5-fluorouracil (fluorouracil) and/or oxaliplatin.
* History of difficulty or inability to take or absorb oral medications.
* Diagnosis of malignancy other than rectal cancer within the past 5 years (excluding completely cured basal cell carcinoma, squamous cell carcinoma of the skin, and/or in situ carcinoma treated with radical resection).
* Confirmed distant metastasis, i.e., cM1, through imaging or biopsy.
* History of pelvic radiotherapy.
* Pregnant or lactating women.
* Presence of any severe or uncontrollable systemic illness.

Primary outcomes:
measure: pCR
timeFrame: 1 year
measure: surgical difficulty
timeFrame: 2 years
Secondary outcomes:
measure: cCR
timeFrame: 2 years
measure: 3-year overal survival rate
timeFrame: 3 years
measure: 5-year overal survival rate
timeFrame: 5 years
measure: 3-year disease free suvival rate
timeFrame: 3 years
measure: 5-year disease free suvival rate
timeFrame: 5 years
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: 3 years
measure: The Late Effects Normal Tissue/Subjective Objective Management Analytic (LENT/SOMA) system
timeFrame: 3 years
measure: Quality of life assessment using the EORTC QLQ-C30 questionnaire
timeFrame: 3 year
measure: Quality of life assessment using the EORTC QLQ-CR29 questionnaire
timeFrame: 3 years
Other outcomes:
Locations:
city: Jinan
country: China
facility: Department of Radiation Oncology, Shandong Cancer Hospital and Institute
state: Shandong
Study officials:
affiliation: Shandong Cancer Hospital and Institute
name: Jinbo Yue, Doctor
role: PRINCIPAL_INVESTIGATOR
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