Induction Therapy With Panitumumab + mFOLFOX-6 in Rectal Cancer and Quadruple Wild-type Mutation Before Surgery

NCT03000374 | Completed Phase 2

• 2 other identifiers: GEMCAD-16012016-002333-29
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 11

Brief Summary

Patients with rectal adenocarcinoma of intermediate risk (defined by magnetic resonance imaging \[MRI\]), without mutations in KRAS, BRAF, NRAS and PI3KCA, who are candidates for preoperative treatment, will receive a preoperative Induction therapy with 12 weeks of panitumumab with mFOLFOX-6 to evaluate the efficacy in terms of pathologic complete response (pCR)

Conditions

Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response (pCR)

  Pathologic CR is defined as the absence of viable tumor cells in the primary tumor and lymph nodes (ypT0N0).

  Up to 16-18 weeks after first treatment administration

Secondary Outcomes (10)

• Rates of R0 resection and free mesorectal fascia (or circumferential margin)

  Up to 16-18 weeks after first treatment administration

• Tumor regression grade (TRG)

  Up to 16-18 weeks after first treatment administration

• Rate of tumor downstaging (mrT versus ypT)

  Up to 16-18 weeks after first treatment administration

• Quality of surgery

  Up to 16-18 weeks after first treatment administration

• Adverse events and changes in laboratory results

  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.

Study Arms (1)

Panitumumab + mFOLFOX-6

EXPERIMENTAL

\- 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

Drug: Panitumumab; Drug: 5Fluorouracil; Drug: Oxaliplatin; Drug: Leucovorin

Interventions

Panitumumab DRUG

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.

Also known as: Vectibix 20 mg/ml

Panitumumab + mFOLFOX-6

5Fluorouracil DRUG

Once every 14 days. Day 1: 400 mg/m2 in IV bolus and a 46-hour infusion of 5-FU 2400 mg/m².

Also known as: 5-FU

Panitumumab + mFOLFOX-6

Oxaliplatin DRUG

Once every 14 days. Day 1: 85 mg/m2 I.V. infusión in 250-500 mL, over two hours, followed by 5-FU

Also known as: Any marketed

Panitumumab + mFOLFOX-6

Leucovorin DRUG

Once every 14 days. Day 1: 200 mg/m2 I.V., over two hours, followed by 5-FU

Also known as: Any marketed

Panitumumab + mFOLFOX-6

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated informed consent form, and willingness and ability to comply with the requirements of the protocol;
• Men or women with rectal cancer, age ≥ 18 and \<75 years;
• Histologically documented adenocarcinoma of the rectum. All other histologic types are excluded. A biopsy of the rectal primary tumor must be available (between 1-4), with tumor representation \> 50% in each sample. The samples will be sent to Val d'Hebron Institute of Oncology (VHIO) for molecular determination. The blocks of the biopsies will be sent included in paraffin.
• Rectal cancer candidate for R0 resection with preservation of the rectal sphincter.
• Tumors with the following characteristics on high-resolution thin-slice (3 mm) MRI:
• mrT3
• Tumors of the middle third, defined as tumors whose distal edge is ≤ 12 cm of the anal verge or below the peritoneal reflection and above ≥ 2 cm of the anorectal junction.
• Absence of MRF invasion, defined as a distance ≥ 1 mm between the tumor and the fascia;
• Absence of mutations in KRAS (mutations in KRAS exon 2 \[codons 12/13\], exon 3 \[codons 59/61\] and exon 4 \[codon 117/146\], NRAS (NRAS exon 2 \[codons 12/13\], exon 3 \[codons 59/61\] and exon 4 \[codons 117/146\]), BRAF (exon 15 \[codon 600\] and PI3KCA in exons 9 and 20
• ECOG performance status ≤ 2;
• Hematological status:
• Neutrophils (ANC) ≥ 1.5 x 109/L;
• Platelets ≥ 100 x 109/L;
• Hemoglobin ≥ 9 g/dL;
• Adequate renal function: serum creatinine \<1.5 x upper limit of normal (ULN);

You may not qualify if:

• Mucinous adenocarcinoma.
• N2 lymph node involvement, defined as: 4 or more lymph nodes in the mesorectum showing morphological signs of metastatic involvement on MRI. A lymph node is considered malignant when:
• Short axis \> 9 mm.
• Short axis 5-9 mm and ≥2 of the following criteria:
• i Rounded appearance. ii Heterogeneous margin. iii Heterogeneous signal intensity.
• Short axis \< 5 mm AND round shape AND heterogeneous margin AND heterogeneous signal intensity.
• Extramesorectal lymph node involvement: an involved extramesorectal lymph node is defined as a lymph node in the obturator area with a short axis \> 8 mm, round shape and heterogeneous signal..
• Prior treatment with panitumumab or cetuximab;
• Preexisting permanent neuropathy (grade ≥ 2 NCI-CTCAE);
• Concomitant antitumor treatment not foreseen in the protocol (e.g., chemotherapy, targeted molecular therapy, immunotherapy);
• Treatment with any other investigational medicinal product within the 28 days prior to study entry;
• Other simultaneous or prior malignancy, except: i) properly treated uterine cervix carcinoma in situ, ii) basal or squamous cell skin carcinoma, iii) cancer in complete remission for a period \> 5 years;
• Evidence of metastatic disease in additional studies or in the physical examination;
• Any other severe and uncontrolled nonmalignant disease, major surgery or traumatic injury in the last 28 days;
• Pregnant or breastfeeding women;

Sponsors & Collaborators

• Grupo Espanol Multidisciplinario del Cancer Digestivo: lead
• Pivotal S.L.: collaborator
• Amgen: collaborator

Study Sites (11)

Hospital General Universitario de Elche

Elche, Alicante, 3203, Spain

Location

Hospital de Sabadell

Sabadell, Barcelona, 08208, Spain

Location

Hospital de Sant Joan Despí Moisés Broggi

Sant Joan Despí, Barcelona, 08970, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Universitari Vall d'Hebrón

Barcelona, 08035, Spain

Location

Hospital Clinic i Provincial

Barcelona, 08036, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Fundación Instituto Valenciano de Oncología

Valencia, 46009, Spain

Location

Consorcio Hospital General Universitario de Valencia

Valencia, 46014, Spain

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Panitumumab; Fluorouracil; Oxaliplatin; Leucovorin

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Carlos Fernández-Martos, MD

  Initia Centro Oncológico Integral

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2016
• First Posted: December 22, 2016
• Study Start: May 30, 2017
• Primary Completion: October 31, 2020
• Study Completion: December 15, 2021
• Last Updated: March 17, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (11)