Induction Therapy With Panitumumab + mFOLFOX-6 in Rectal Cancer and Quadruple Wild-type Mutation Before Surgery (PIER)
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|ClinicalTrials.gov Identifier: NCT03000374|
Recruitment Status : Completed
First Posted : December 22, 2016
Last Update Posted : March 17, 2022
|Condition or disease||Intervention/treatment||Phase|
|Rectal Cancer||Drug: Panitumumab Drug: 5Fluorouracil Drug: Oxaliplatin Drug: Leucovorin||Phase 2|
Phase II, nonrandomized single-arm trial of preoperative treatment with mFOLFOX-6 and panitumumab in an enriched population of patients with rectal adenocarcinoma of intermediate risk, screened by MRI, without mutations in KRAS, BRAF, NRAS and PI3K. All patients enrolled in the study will receive 12 weeks of the investigational product (mFOLFOX-6 with panitumumab) every 14 days for six cycles, unless unacceptable toxicity occurs or progression is detected. After this treatment, response will be evaluated by diffusion-weighted MRI and endoscopy. In the absence of disease progression, patients eligible for R0 resection will undergo total mesorectal excision (TME). After surgery, patients will receive mFOLFOX6 x 6 cycles. In the case of intolerance to FOLFOX-panitumumab, disease progression or ineligibility for R0 resection, patients will receive chemoradiotherapy with capecitabine 825 mg/m2 every 12 hours concomitantly with radiotherapy (RT) with a total dose of 50.4 Gy. At the end of this treatment, patients will undergo TME between 6-8 weeks after finishing the CRT. If a patient has received 4 or more neoadjuvant cycles of FOLFOX-panitumumab before unacceptable toxicity or progression, it will be considered that the neoadjuvant treatment has been completed and the patient will have no additional neoadjuvant treatment but surgery. If the patient has received <4 cycles of neoadjuvant treatment, neoadjuvant CRT will be administered.
If a patient has an acceptable toxicity or disease progression or a R0 surgery is not possible to be performed and the patient received CRT, the patient will be followed up for 24 months, from the enrollment of the last patient in the trial, or until progression occurs, in order to assess progression-free survival and all the data regarding surgery and CRT will be recorded in the eCRF. If a patient withdraws consent and refuses to continue participating in the study, follow-up evaluations must be discontinued.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||34 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Preoperative Induction Therapy With 12 Weeks of Panitumumab in Combination With mFOLFOX-6 in an Enriched Population (Quadruple Wild-Type) of Patients With mrT3 Rectal Cancer of the Middle Third With Clear Mesorectal Fascia|
|Actual Study Start Date :||May 30, 2017|
|Actual Primary Completion Date :||October 31, 2020|
|Actual Study Completion Date :||December 15, 2021|
Experimental: Panitumumab + mFOLFOX-6
- Modified FOLFOX-6 regimen: 5-Fluorouracil (5-FU), oxaliplatin and leucovorin will be administered intravenously once every 14 days, according to the mFOLFOX-6 regimen:
Day 1: Oxaliplatin 85 mg/m² in IV infusion of 250-500 mL and leucovorin 200 mg/m² IV, both injected over two hours, followed by 5-FU 400 mg/m2 in IV bolus and a 46-hour infusion of 5-FU 2400 mg/m².
- Panitumumab will be administered intravenously (IV) in a dose of 6 mg/kg on day 1 every 14 days. Panitumumab will be supplied to sites by the study sponsor in 5-mL and 20-mL vials, at a concentration of 20 mg/mL.
Treatment will continue until 6 cycles have been administered, followed by surgery, 5 weeks +/- 1 week after the last dose of neoadjuvant treatment
Panitumumab will be administered intravenously (IV) in a dose of 6 mg/kg on day 1 every 14 days. Panitumumab will be supplied to sites by the study sponsor in 5-mL and 20-mL vials, at a concentration of 20 mg/mL.
Other Name: Vectibix 20 mg/ml
Once every 14 days. Day 1: 400 mg/m2 in IV bolus and a 46-hour infusion of 5-FU 2400 mg/m².
Other Name: 5-FU
Once every 14 days. Day 1: 85 mg/m2 I.V. infusión in 250-500 mL, over two hours, followed by 5-FU
Other Name: Any marketed
Once every 14 days. Day 1: 200 mg/m2 I.V., over two hours, followed by 5-FU
Other Name: Any marketed
- Pathologic complete response (pCR) [ Time Frame: Up to 16-18 weeks after first treatment administration ]Pathologic CR is defined as the absence of viable tumor cells in the primary tumor and lymph nodes (ypT0N0).
- Rates of R0 resection and free mesorectal fascia (or circumferential margin) [ Time Frame: Up to 16-18 weeks after first treatment administration ]
- Tumor regression grade (TRG) [ Time Frame: Up to 16-18 weeks after first treatment administration ]the residual tumor after preoperative treatment is evaluated semi-quantitatively using the 5-point regression grading scale established by Dworak
- Rate of tumor downstaging (mrT versus ypT) [ Time Frame: Up to 16-18 weeks after first treatment administration ]
- Quality of surgery [ Time Frame: Up to 16-18 weeks after first treatment administration ]According to the histopathology report
- Adverse events and changes in laboratory results [ Time Frame: All AEs that occur up until 30 days after the last dose of investigational product will be recorded. Serious and nonserious AEs related with the study treatment that appear up until 30 days after the administration of the last dose should be reported. ]The adverse events will be encoded using the Medical Dictionary for Regulatory Activities (MedDRA), version 18.1 or later, and evaluated using the U.S. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 4.0.
- Surgical complications [ Time Frame: Over 30 days after surgery. ]
- Rate of local recurrence [ Time Frame: At 3 years after recruitment ]
- Distant metastasis rate [ Time Frame: At 3 years after recruitment ]
- Disease free survival [ Time Frame: At 3 years after recruitment ]
- Overall survival [ Time Frame: At 3 years after recruitment ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03000374
|Hospital General Universitario de Elche|
|Elche, Alicante, Spain, 3203|
|Hospital de Sabadell|
|Sabadell, Barcelona, Spain, 08208|
|Hospital de Sant Joan Despí Moisés Broggi|
|Sant Joan Despí, Barcelona, Spain, 08970|
|Complejo Hospitalario de Navarra|
|Pamplona, Navarra, Spain, 31008|
|Hospital de la Santa Creu i Sant Pau|
|Barcelona, Spain, 08025|
|Hospital Universitari Vall d'Hebrón|
|Barcelona, Spain, 08035|
|Hospital Clinic i Provincial|
|Barcelona, Spain, 08036|
|Hospital Universitario La Paz|
|Madrid, Spain, 28046|
|Hospital Universitario Virgen del Rocío|
|Sevilla, Spain, 41013|
|Fundación Instituto Valenciano de Oncología|
|Valencia, Spain, 46009|
|Consorcio Hospital General Universitario de Valencia|
|Valencia, Spain, 46014|
|Study Director:||Carlos Fernández-Martos, MD||Initia Centro Oncológico Integral|