Anti-EGFR Therapy Rechallenge in Combination With Chemotherapy in Patients With Advanced Colorectal Cancer

NCT03311750 | Terminated Phase 2

• 2 other identifiers: HE6B/162016-003644-37
• Study Type: interventional
• Target: 23
• Locations: 2 countries
• Sites: 8

Brief Summary

A-REPEAT (Anti-Epidermal Growth Factor Receptor -EGFR- rechallenge and plasma genotyping of patients with advanced colorectal tumors) is a Greek, investigator-initiated, single arm open-label phase II study of anti-EGFR therapy rechallenge in combination with chemotherapy in patients with advanced colorectal cancer. Patients with a metastatic, histologically proven colorectal carcinoma RAS wild type will be treated with a combination of panitumumab and third-line irinotecan-based or oxaliplatin-based chemotherapy (FOLFOX,FOLFIRI or irinotecan monotherapy).

Conditions

Advanced Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Evaluation of overall response rate of the addition of panitumumab rechallenge to standard third-line therapy

  Evaluation of efficacy of overall response rate, of the addition of panitumumab rechallenge to standard third-line irinotecan-based or oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer initially treated with, and benefiting from, first line irinotecan-based or oxaliplatin-based chemotherapy combined with an anti-EGFR monoclonal antibody, followed by second line chemotherapy not containing anti-EGFR agents.

  At baseline, every 8 weeks with a 2-week tumor evaluation window through study completion, an average of 30 months.

Secondary Outcomes (13)

• Evaluation of overall response rate by RAS status

  At baseline, every 8 weeks with a 2-week tumor evaluation window through study completion, an average of 30 months.

• Evaluation of Progression Free Survival

  From study entry to disease progression or death due to any cause assessed up to 30 months

• Evaluation of Overall Survival

  From study entry until date of death due to any cause or last contact assessed up to 30 months

• Evaluation of safety of the combination of standard 3rd-line irinotecan-based or oxaliplatin-based chemotherapy with panitumumab rechallenge.

  Per cycle (each cycle is repeated every 2 weeks for FOLFIRI and FOLFOX regimens and every 3 weeks for irinotecan monotherapy) assessed up to 30 months.

• Mutation status of KRAS gene

  At baseline

Study Arms (1)

Panitumumab

EXPERIMENTAL

On day 1 of each cycle patients will receive panitumumab followed by 5-fluorouracil and leucovorin in combination with either irinotecan (FOLFIRI regimen) or oxaliplatin (FOLFOX regimen) or followed by irinotecan monotherapy. This treatment will be repeated every 2 weeks for FOLFIRI and FOLFOX regimens and every 3 weeks for irinotecan monotherapy.

Drug: Panitumumab

Interventions

Panitumumab DRUG

6 mg/Kg will be administered intravenous over 1 hour on Day 1 every 2 weeks or 9 mg/Kg every 3 weeks.

Also known as: Vectibix

Panitumumab

Eligibility Criteria

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

You may qualify if:

• Signed and dated informed consent, and willing and able to comply with protocol requirements,
• Histologically proven adenocarcinoma of the colon and/or rectum,
• Metastatic disease confirmed clinically/radiologically,
• Patients with Formalin-Fixed, Paraffin-Embedded tissue RAS wild type colorectal cancer at diagnosis, who had initial clinical benefit \[complete response, partial response or stable disease\] during first line irinotecan-based or oxaliplatin-based chemotherapy in combination with cetuximab or panitumumab,
• First- line treatment duration (FOLFIRI, FOLFOX with anti-EGFR monoclonal antibody, of whom at least 2/3 of cases will have involved panitumumab) of at least 3 months,
• Second line therapy consisting of any chemotherapy (with or without Bevacizumab) definitely without anti-EGFR therapy of at least 2 months, followed by disease progression,
• Eligible third line regimens include FOLFIRI or Irinotecan or FOLFOX, according to standard practice and approved indications. It is required that the third line regimen used will be different from the second line and similar to the first line regimen,
• At least one measurable or evaluable lesion as assessed by computed tomography scan or Magnetic Resonance Imaging according to RECIST version 1.1,
• First course of treatment planned less than 1 week (7 days) after registration,
• Age ≥18 years,
• Eastern Cooperative Oncology Group (ECOG) Performance status 0-2,
• Adequate hematological status: neutrophils (ANC) ≥1.5x109/L; platelets ≥100x109/L; haemoglobin ≥9g/dL,
• Adequate renal function: serum creatinine level \<1.5 mg/dL or Glomelular Filtration Rate (GFR) \>50mL/min by Cockroft/Gault formula,
• Adequate liver function: serum bilirubin ≤1.5 x upper normal limit (ULN), alkaline phosphatase, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) \<5xULN,
• Regular follow up feasible.

You may not qualify if:

• Presence of central nervous system metastasis unless adequately treated (e.g. non irradiated central nervous system metastasis, seizures not controlled with standard medical therapy constitute non-eligibility criteria),
• Active infection (ie, body temperature ≥38°C due to infection),
• Intestinal obstruction, pulmonary fibrosis or interstitial pneumonitis, renal failure, liver failure, or cerebrovascular disorder,
• Uncontrolled diabetes,
• Myocardial infarction within the last 6 months, severe/unstable angina, symptomatic congestive heart failure New York Heart Association class III or IV,
• Known human immunodeficiency virus or acquired immunodeficiency syndrome-related illness, or hepatitis B or C,
• Autoimmune disorders or history of organ transplantation that require immunosuppressive therapy,
• Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for \>5 years,
• Major surgery or traumatic injury within the last 28 days,
• Pregnant or breastfeeding women,
• Patients with known allergy to any excipients to study drugs,
• Other serious and uncontrolled chronic non-malignant disease,
• Known dihydropyrimidine dehydrogenase deficiency,
• Palliative radiation therapy within 4 weeks prior to registration,
• Life expectancy less than 12 weeks in the opinion of the Investigator,

Sponsors & Collaborators

• Hellenic Cooperative Oncology Group: lead
• Amgen: collaborator

Study Sites (8)

Bank Of Cyprus Oncology Centre

Stróvolos, Nicosia, 2006, Cyprus

Location

"Attikon" University Hospital

Chaïdári, Athens, 12462, Greece

Location

University Hospital of Heraklion

Heraklion, Crete, 71110, Greece

Location

Ioannina University Hospital

Ioannina, Ioannina, 45500, Greece

Location

Agii Anargiri Cancer Hospital

Athens, Kalyftaki, Nea Kifisia, 14564, Greece

Location

Metropolitan Hospital

Athens, Neo Faliro, 18547, Greece

Location

University Hospital of Patra

Rio, Patra, 26504, Greece

Location

Euromedica General Clinic of Thessaloniki

Thessaloniki, Thessaloniki, 54645, Greece

Location

MeSH Terms

Interventions

Panitumumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Joseph Sgouros, MD

  3rd Department of Medical Oncology,Agii Anargiri Cancer Hospital

  PRINCIPAL INVESTIGATOR

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: October 2, 2017
• First Posted: October 17, 2017
• Study Start: March 26, 2018
• Primary Completion: March 31, 2021
• Study Completion: May 20, 2021
• Last Updated: June 7, 2021

Record last verified: 2021-06

Locations

GR (7); CY (1)