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Panitumumab and RAS, DIagnostically-useful Gene Mutation for mCRC). (PARADIGM)

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ClinicalTrials.gov Identifier: NCT02394795
Recruitment Status : Active, not recruiting
First Posted : March 20, 2015
Last Update Posted : November 14, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda

Brief Summary:
The purpose of this study is to verify the efficacy of mFOLFOX6 + panitumumab combination therapy and mFOLFOX6 + bevacizumab combination therapy in first-line treatment of chemotherapy-naive patients with KRAS/NRAS wild-type, incurable/unresectable, advanced/recurrent colorectal cancer.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Drug: oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, panitumumab Drug: oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, bevacizumab Phase 3

Detailed Description:

The purpose of this study is to verify the efficacy of mFOLFOX6 + panitumumab combination therapy and mFOLFOX6 + bevacizumab combination therapy in first-line treatment of chemotherapy-naive patients with KRAS/NRAS wild-type, incurable/unresectable, advanced/recurrent colorectal cancer.

This study will enroll a total of 800 participants (400 per group). Patients will be randomized to either the mFOLFOX6 + panitumumab arm (Group P) or mFOLFOX6 + bevacizumab arm (Group B) at 1:1 ratio at the time of registration.

Group P and Group B treatment regimen shown below should be administered once every two weeks, following dose, schedule and route of administration.

Group P; mFOLFOX6 + panitumumab combination therapy, once every two weeks OXA: 85 mg/m2/day 1 LV: 200 mg/m2/day 15-FU iv: 400 mg/m2/day 1 5-FU civ: 2400 mg/m2/day 1-3 panitumumab: 6 mg/kg

Group B; mFOLFOX6 + bevacizumab combination therapy, once every two weeks OXA: 85 mg/m2/day 1 LV: 200 mg/m2/day 1 5-FU iv: 400 mg/m2/day 1 5-FU civ: 2400 mg/m2/day 1-3 bevacizumab: 5 mg/kg/

This trial is conducted by multicenter and is scheduled for 12 months as whole administration period. As an additional study of the main study to investigate biomarkers exploratory which may be predictors of Panitumumab and Bevacizumab efficacy, using tumor issue and blood sample before treatment.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 823 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Controlled Study of mFOLFOX6 + Bevacizumab Combination Therapy Versus mFOLFOX6 + Panitumumab Combination Therapy in Chemotherapy-naive Patients With KRAS/NRAS Wild-type, Incurable/Unresectable, Advanced/Recurrent Colorectal Cancer
Actual Study Start Date : April 1, 2015
Estimated Primary Completion Date : March 1, 2020
Estimated Study Completion Date : March 1, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group P; mFOLFOX6 + panitumumab combination therapy
OXA: 85 mg/m2/day 1 LV: 200 mg/m2/day 1 5-FU iv: 400 mg/m2/day 1 5-FU civ: 2400 mg/m2/day 1-3 panitumumab: 6 mg/kg mFOLFOX6 + panitumumab combination therapy, once every two weeks
Drug: oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, panitumumab
Other Names:
  • oxaliplatin (OXA), levofolinate calcium (l-LV), panitumumab: intra-venous infusion
  • 5-FU: bolus and continuous intra-venous infusion

Active Comparator: Group B; mFOLFOX6 + bevacizumab combination therapy
OXA: 85 mg/m2/day 1 LV: 200 mg/m2/day 1 5-FU iv: 400 mg/m2/day 1 5-FU civ: 2400 mg/m2/day 1-3 bevacizumab: 5 mg/kg/ mFOLFOX6 + bevacizumab combination therapy, once every two weeks
Drug: oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, bevacizumab
Other Names:
  • oxaliplatin (OXA), levofolinate calcium (l-LV), bevacizumab: intra-venous infusion
  • 5-FU: bolus and continuous intra-venous infusion




Primary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: Up to 60 month ]
    OS will be measured as the time from the date of randomization to the date of death.


Secondary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: Up to 10 month ]
    PFS is defined as the time from the date of randomization to the date of first documentation of disease progression, as evaluated by an independent review committee according to International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occurs first.

  2. Percentage of Participants who Achieve or Maintain Any Best Response Category during the Treatment Period. [ Time Frame: Up to 10 month ]
    Percentage of Participants who Achieve or Maintain Any Best Response Category during the Treatment Period. Response was assessed according to IMWG criteria. Best response includes partial response (PR) and complete response (CR)

  3. Duration of response (DOR) [ Time Frame: Up to 10 months ]
    DOR means that the period from the day when either CR or PR is first confirmed until the day of documented PD or the day of death due to all causes, whichever occurs earlier.

  4. Percentage of participants treated with surgical resection after chemotherapy [ Time Frame: Up to 10 month ]
    TTF is defined as the period from the date of randomization (counted as Day 0) to the date of judgment of discontinuation of protocol treatment, the date of judgment of progression, or the date of death for all causes, whichever has come earliest.

  5. Percentage of participants with adverse events [ Time Frame: Up to 10 month ]
    Adverse events are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug. Either the day 28 days later protocol treatment discontinued or the day second-line started, whichever occurs earlier.



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Investigator and subinvestigator judge a candidate is understand clinical trial and comply this protocol.

    Investigator is those who participate in conducting a study and oversight the study duties at a site.

  2. Patients who have given written consent to take part in the study after detailed explanation of the study prior to enrollment
  3. Aged ≥20 to <80 years at the time of informed consent
  4. Patients with unresectable adenocarcinoma originating in the large intestine (excluding carcinoma of the appendix and anal canal cancer)
  5. Patients with lesion(s) that can be evaluated. It is not essential to be evaluated the tumor according to the RECIST ver. 1.1.
  6. Patients who have not received chemotherapy for colorectal cancer. Patients who experience relapse more than 24 weeks (168 days) after the final dose of perioperative adjuvant chemotherapy with fluoropyrimidine agents may be enrolled. Patients who have received perioperative adjuvant chemotherapy including oxaliplatin are excluded.
  7. Patients classified as KRAS/NRAS wild-type by KRAS/NRAS testing. KRAS/NRAS test will be performed using the in vitro diagnostic listed in the National Health Insurance.

    Patients with no mutation in any of the codons shown below are considered wild type. It is not considered wild type if either of the codons are not evaluable or not tested.

    KRAS: EXON2 (codon 12, 13), EXON3 (codon 59, 61), EXON4 (codon 117, 146) NRAS:EXON2 (codon 12, 13), EXON3 (codon 59, 61), EXON4 (codon 117, 146)

  8. Patients who satisfy the following criteria for the major organ function in tests performed within 14 days prior to enrollment

    • Neutrophil count ≥ 1.5×103/µL
    • Platelet count ≥ 1.0×104/µL
    • Hemoglobin ≥ 9.0 g/dL
    • Total bilirubin ≤ 2.0 mg/dL
    • AST ≤ 100 IU/L (≤ 200 IU/L if liver metastases are present)
    • ALT ≤ 100 IU/L (≤ 200 IU/L if liver metastases are present)
    • Serum creatinine ≤ 1.5 mg/dL
    • PT-INR < 1.5 (< 3.0 for patients treated with oral warfarin)
    • Satisfies at least one of these conditions (i) Urine protein (dip stick method) ≤ 1+ (ii) UPC (urine protein creatinine) ratio ≤ 1.0 (iii) Urinary protein ≤ 1000mg/ 24hours
  9. ECOG performance status (PS) of 0 or 1
  10. Life expectancy of ≥ 3 months (90 days) after enrollment

Exclusion Criteria:

  1. Radiotherapy received within 4 weeks (28 days) prior to enrollment. Treatments aimed at relieving pain for bone metastases are excluded.
  2. Known brain metastasis or strongly suspected of brain metastasis
  3. Synchronous cancers or metachronous cancers with a disease-free period of ≤ 5 years (excluding colorectal cancer) excluding mucosal cancers cured or be possibly cured by regional resection (esophageal, stomach, and cervical cancer, non-melanoma skin cancer, bladder cancer, etc.).
  4. Body cavity fluid that requires treatment (pleural effusion, ascites, pericardial effusion, etc.)
  5. Patients who do not want to use contraception to prevent pregnancy, and women who are pregnant or breast-feeding, or test positive for pregnancy
  6. Nonhealing surgical wound (excluding implanted venous reservoirs)
  7. Active hemorrhage requiring blood transfusion
  8. Disease requiring systemic steroids for treatment (excluding topical steroids)
  9. The patient who has placed colonic stent
  10. Intestinal resection within 4 weeks prior to enrollment or colostomy within 2 weeks prior to enrollmentt
  11. History or obvious and extensive CT findings of interstitial pulmonary disease (interstitial pneumonia, pulmonary fibrosis, etc.)
  12. Patients with unstable angina, myocardial infarction, cerebral hemorrhage, arterial thromboembolism such as cerebral infarction, or have history of these desease less than 24 weeks (168 days) before registration (except for lacunar infarction asymptomatic)
  13. Serious drug hypersensitivity
  14. Local or systemic active infection requiring treatment, or fever indicating infection
  15. NYHA class II or higher heart failure or serious heart disease
  16. Intestinal paralysis, gastrointestinal obstruction, or uncontrollable diarrhoea (incapacitating symptoms despite adequate treatment)
  17. Poorly controlled hypertension
  18. Poorly controlled diabetes mellitus
  19. Active hepatitis B
  20. Known HIV infection
  21. Peripheral neuropathy of ≥ Grade 2 by CTCAE (Japanese edition JCOG version 4.03)
  22. Other patients judged by the investigator or subinvestigator to be ineligible for enrollment in the study (e.g. Patients who might agree to participate under compulsion).

Information from the National Library of Medicine

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): NCT02394795


  Show 155 Study Locations
Sponsors and Collaborators
Takeda
Investigators
Study Director: General Manager Takeda

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02394795     History of Changes
Other Study ID Numbers: Panitumumab-3001
U1111-1164-9167 ( Other Identifier: WHO )
JapicCTI-142731 ( Registry Identifier: JapicCTI )
First Posted: March 20, 2015    Key Record Dates
Last Update Posted: November 14, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Takeda:
Metastatic colorectal cancer, Panitumumab, mFOLFOX6, Bevacizumab

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Oxaliplatin
Fluorouracil
Leucovorin
Calcium, Dietary
Antibodies, Monoclonal
Levoleucovorin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Bone Density Conservation Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors