Panitumumab-based Maintenance in Patients With RAS Wild-type, Metastatic Colorectal Cancer (Valentino)

NCT02476045 | Unknown Phase 2

• 1 other identifier: INT 70/15
• Study Type: interventional
• Target: 224
• Locations: 1 country
• Sites: 1

Brief Summary

Open label, randomized, multicenter, phase II study to compare the efficacy, in terms of non-inferiority of progression-free survival (PFS), of maintenance with panitumumab alone (arm B) as compared to panitumumab with 5-fluorouracil (5-FU) and leucovorin (LV) (arm A) following induction treatment with 5-fluorouracil + leucovorin+oxaliplatin (FOLFOX-4) and panitumumab in patients with RAS wild-type, metastatic colorectal cancer. The study involves an induction phase with panitumumab as 1 hour intravenous infusion at the dosage of 6 mg/kg, given every two weeks, plus FOLFOX-4 chemotherapy as standard guidelines. Before start of FOLFOX-4 plus panitumumab, at the time of enrollment, patients will be immediately randomized electronically 1:1 to one of the two maintenance arms. Induction treatment with FOLFOX-4 plus panitumumab will continue until progressive disease, unacceptable toxicity or informed consent withdrawal, or for up to 8 cycles. At the end of induction treatment, in presence of complete or partial response, or stable disease, non-progressing patients will be allocated to one of the two pre-assigned maintenance arms: A) 5-FU/LV (De Gramont regimen) plus panitumumab given at 6 mg/Kg every two weeks until progressive disease, unacceptable toxicity or informed consent withdrawal B) Panitumumab alone given at 6 mg/Kg every two weeks until progressive disease, unacceptable toxicity or informed consent withdrawal Imaging studies (thorax and abdominal CT or MRI scan) will be performed at baseline (4 weeks prior enrollment) and every 8 weeks (4 cycles) during treatment.

Conditions

Metastatic Colorectal Cancer

Keywords

metastatic colorectal cancer; RAS wild-type; maintenance therapy; panitumumab

Outcome Measures

Primary Outcomes (1)

• Efficacy

  in terms of progression free survival (from the enrollment)

  3 years

Secondary Outcomes (7)

• Safety in terms of number of participants with adverse events.

  3 years

• Quality of life

  3 years

• Response rate

  3 years

• duration of response

  3 years

• time to progression

  3 years

Study Arms (2)

ARM A

ACTIVE COMPARATOR

Induction phase with panitumumab as 1 hour intravenous infusion at the dosage of 6 mg/kg, given every two weeks, plus FOLFOX-4 chemotherapy as standard guidelines. Maintenance therapy with 5-FU/LV (De Gramont regimen) plus panitumumab given at 6 mg/Kg every two weeks until progressive disease, unacceptable toxicity or informed consent withdrawal

Drug: 5-fluorouracil,leucovorin,panitumumab; Drug: Oxaliplatin, 5-fluorouracil,leucovorin,panitumumab

ARM B

EXPERIMENTAL

Induction phase with panitumumab as 1 hour intravenous infusion at the dosage of 6 mg/kg, given every two weeks, plus FOLFOX-4 chemotherapy as standard guidelines. Maintenance therapy with panitumumab alone given at 6 mg/Kg every two weeks until progressive disease, unacceptable toxicity or informed consent withdrawal

Drug: panitumumab; Drug: Oxaliplatin, 5-fluorouracil,leucovorin,panitumumab

Interventions

5-fluorouracil,leucovorin,panitumumab DRUG

Maintenance treatment (ARM A)

ARM A

panitumumab DRUG

Maintenance treatment (ARM B)

ARM B

Oxaliplatin, 5-fluorouracil,leucovorin,panitumumab DRUG

Induction treatment

Also known as: FOLFOX-4 + panitumumab

ARM A; ARM B

Eligibility Criteria

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

You may qualify if:

• Written informed consent prior to performance of any study procedure;
• Age ≥18 years;
• ECOG Performance Status 0-1;
• Life expectancy of at least 12 weeks in the opinion of the Investigator;
• Histologically or cytologically confirmed adenocarcinoma of the colon or rectum, with RAS wild-type status;
• Metastatic unresectable colorectal cancer not previously treated with standard chemotherapy for advanced or metastatic disease;
• Measurable or non-measurable metastatic lesion(s), as defined by RECIST version 1.1;
• Laboratory requirements:
• Neutrophils \>= 1.5 x 109/L, Platelets \>= 100 x 109/L, and Haemoglobin \>=10g/dL
• Total bilirubin \<= 1.5 time the upper-normal limits (UNL) of the Institutional normal values; ASAT (SGOT) and/or ALAT (SGPT) \<= 2.5 x UNL, or \<= 5 x UNL in case of liver metastases; alkaline phosphatase \<= 2.5 x UNL, \<= 5 x UNL in case of liver metastases, \<= 10 x UNL in case of bone metastases; LDH \<1500 U/L
• Creatinine clearance (calculated according to Cockcroft and Gault) \> 60 mL/min or serum creatinine \<=1.5 x upper limit of normal (UNL);
• Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating center.
• Archival tumor tissue is required for exploratory research at enrolment.

You may not qualify if:

• Has a serious illness or medical condition(s) including, but not limited to the following:
• Other concurrently active malignancies excluding malignancies that are disease free for more than 5 years or carcinoma-in-situ deemed cured by adequate treatment.
• Known brain metastasis or leptomeningeal metastasis.
• Active infection (ie, body temperature ≥38°C due to infection).
• Ascites, pleural effusion or pericardial fluid requiring drainage in last 4 weeks.
• Intestinal obstruction, pulmonary fibrosis or interstitial pneumonitis, renal failure, liver failure, or cerebrovascular disorder.
• Uncontrolled diabetes.
• Myocardial infarction within the last 12 months, severe/unstable angina, symptomatic congestive heart failure New York Heart Association (NYHA) class III or IV
• Gastrointestinal hemorrhage.
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or hepatitis B or C.
• Autoimmune disorders or history of organ transplantation that require immunosuppressive therapy.
• Psychiatric disease that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results.
• Patients who had received adjuvant oxaliplatin-based chemotherapy and had recurrence during treatment or within 12 months from its completion are excluded. Patients who had received adjuvant fluoropyrimidine mono-therapy and had recurrence during treatment or within 6 months from its completion are excluded.
• Disease that is deemed potentially resectable after conversion chemotherapy is excluded. In particular, patients must be deemed unresectable by a multidisciplinary team, even when foreseeing a response to treatment. In case of liver metastases, the concept of resectability must take into account both the aim of oncological radicality (R0 resection) and remanent liver function considerations.
• Treatment with any of the following within the specified time frame prior to study drug administration:

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei tumori

Milan, MI, 20133, Italy

RECRUITING

Related Publications (2)

• Morano F, Corallo S, Lonardi S, Raimondi A, Cremolini C, Rimassa L, Murialdo R, Zaniboni A, Sartore-Bianchi A, Tomasello G, Racca P, Clavarezza M, Adamo V, Perrone F, Gloghini A, Tamborini E, Busico A, Martinetti A, Palermo F, Loupakis F, Milione M, Fuca G, Di Bartolomeo M, de Braud F, Pietrantonio F. Negative Hyperselection of Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer Who Received Panitumumab-Based Maintenance Therapy. J Clin Oncol. 2019 Nov 20;37(33):3099-3110. doi: 10.1200/JCO.19.01254. Epub 2019 Sep 20.

  PMID: 31539295 DERIVED

• Pietrantonio F, Morano F, Corallo S, Miceli R, Lonardi S, Raimondi A, Cremolini C, Rimassa L, Bergamo F, Sartore-Bianchi A, Tampellini M, Racca P, Clavarezza M, Berenato R, Caporale M, Antista M, Niger M, Smiroldo V, Murialdo R, Zaniboni A, Adamo V, Tomasello G, Giordano M, Petrelli F, Longarini R, Cinieri S, Falcone A, Zagonel V, Di Bartolomeo M, de Braud F. Maintenance Therapy With Panitumumab Alone vs Panitumumab Plus Fluorouracil-Leucovorin in Patients With RAS Wild-Type Metastatic Colorectal Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2019 Sep 1;5(9):1268-1275. doi: 10.1001/jamaoncol.2019.1467.

  PMID: 31268481 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Fluorouracil; Panitumumab; Oxaliplatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals

Central Study Contacts

Filippo Pietrantonio, MD

CONTACT

022390; filippo.pietrantonio@istitutotumori.mi.it

Monica Niger, MD

CONTACT

022390; monica.niger@istitutotumori.mi.it

Study Design

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

Study Record Dates

• First Submitted: June 11, 2015
• First Posted: June 19, 2015
• Study Start: June 1, 2015
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: September 14, 2016

Record last verified: 2016-09

Locations

IT (1)