Clinical trial NCT02942563: Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer
Official title: A Phase II Study of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Rectal Cancer
Keywords: Local Advanced Rectal Cancer
Total Neoadjuvant Therapy
FOLFOXIRI
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
First posted: 2016-10-24
Enrollment: 100
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: The concurrent neoadjuvant chemoradiation therapy is standard care for local advanced rectal cancer (LARC), however, this regimen may induce sorts of adverse events, and part of them even more severer. A number of pilot studies had shown high rate of complete resection after neoadjuvant chemotherapy alone, but the results did not increase the ratio of pathological complete response (pCR), which was associated with overall survival (OS). Here, the investigators adopt the three active cytotoxic agents (Fluorouracil, Oxaliplatin, Irinotecan, FOLFOXIRI) as the neoadjuvant chemotherapy regimen to replace the concurrent chemoradiation and to improve the ratio of pCR further.

Detailed description: This is a multicenter, phase II trial to assess the efficacy/safety of triplet regimen (FOLFOXIRI) for patients with LARC. After 4 cycles of FOLFOXIRI and 2 weeks later, the patients will be evaluated by senior radiologist, oncologist and surgeon through pelvic MRI, CT and Positron Emission Computed Tomography (PET-CT). The patients will go to surgery (TME) if the tumor response is good enough to have complete resection under the decision of MDT,otherwise, the patients will receive pelvic radiotherapy(45Grey/25Fraction and 5.4Grey/3Fraction boost to the tumor bed) combined with capecitabine(625mg/M\^2, bid po, d1-5, qw), and additional four cycles of modified FOLFOX6 (mFOLFOX6) or Oxaliplatin 135mg/m²plus Capecitabine 1.0/m² bid po(XELOX) of each 3 weeks cycle for 2 cycles chemotherapy before TME. All patients will receive 6-8 cycles of mFOLFOX6 or 4-5 cycles XELOX as adjuvant chemotherapy after TME.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 to 75 years at diagnosis
* Diagnosis of rectal adenocarcinoma
* ECOG status: 0～1
* Clinical stage II (T3-4, N0) or stage III (T1-4, N1-2)
* Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment:
* Leukocytes ≥ 4.0 x109/ L,
* Absolute neutrophil count (ANC) ≥ 2.0 x109/ L
* Platelet count ≥ 100 x109/ L,
* Hemoglobin (Hb) ≥ 9g/ dL.
* Total bilirubin ≤1.5 x the upper limit of normal (ULN).
* Alanine aminotransferase (ALT) ≤ 3 x ULN
* Aspartate aminotransferase (AST) ≤ 3 x ULN.
* Serum creatinine ≤ 1.5 x the ULN.
* Signed informed consent;

Exclusion Criteria:

* Patient had received pelvic radiotherapy
* Patient had received systemic chemotherapy
* Pregnant and Nursing women
* Had metastatic disease
* Uncontrolled co-morbid illnesses or other concurrent disease
* Patient had second malignant disease within 5 years
* Patients refused to signed informed consent.

Primary outcomes:
measure: Pelvic complete resection rate
timeFrame: Up to 10 weeks
Secondary outcomes:
measure: The rate of local control
timeFrame: 3 years
measure: Disease free survival (DFS)
timeFrame: 3 years
measure: Overall survival
timeFrame: 3 years
measure: The rate of receive chemoradiation
timeFrame: Up to 10 weeks
measure: The rate of clinical complete response after 4 cycles of FOLFOXIRI
timeFrame: Up to 10 weeks
measure: The rate of pathological complete response after 4 cycles of FOLFOXIRI
timeFrame: Up to 10 weeks
measure: The incidence of >=3 grade adverse events
timeFrame: 2 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ethics Committee of Renji Hospital, School of Medicine,Shanghai Jiaotong University
state: Shanghai
Study officials:
affiliation: Locations: China, Shanghai Shanghai Jiaotong University School of Medicine, Renji Hospital
name: Ming Ye, Master
role: PRINCIPAL_INVESTIGATOR
References: