Panitumumab Regimen Evaluation in Colorectal Cancer to Estimate Primary Response to Treatment (PRECEPT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00411450
First received: December 12, 2006
Last updated: January 15, 2016
Last verified: January 2016
  Purpose
The primary objective is to estimate the effect of the human homolog of the Kirsten rat sarcoma-2 virus oncogene (KRAS) mutation status (wild type versus mutant) from tumor tissue on efficacy endpoints in patients with metastatic colorectal cancer (mCRC) receiving second-line chemotherapy with panitumumab after failing first-line treatment.

Condition Intervention Phase
Colon Cancer
Colorectal Cancer
Rectal Cancer
Cancer
Metastatic Cancer
Metastatic Colorectal Cancer
Oncology
Biological: Panitumumab
Drug: FOLFIRI
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multi Center, Open Label, Single Arm Trial Evaluating Panitumumab in Combination With FOLFIRI Therapy Following First Line FOLFOX and Bevacizumab Treatment of Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Objective Response Rate at Weeks 17 and 25 [ Time Frame: Week 17 and Week 25 ] [ Designated as safety issue: No ]
    Objective response rate is defined as the percentage of participants with a best response of complete response or partial response. Disease assessments were based on investigator review of scans using modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria. A complete or partial response was confirmed no less than 4 weeks after the criteria for response were first met. Participants with no radiographic tumor assessment(s) at Week 17 or 25 were considered non-responders. Complete Response (CR): disappearance of all target and non-target lesions and no new lesions. Partial Response (PR): At least a 30% decrease in the size of target lesions with no progression of non-target lesions (defined as a ≥ 25% increase in lesion size) and no new lesions, or, the disappearance of all target lesions but persistence of 1 or more non-target lesions not qualifying for either CR or progressive disease (PD) and no new lesions.

  • Best Response During Second-Line Treatment [ Time Frame: Tumor response was assessed at Weeks 9, 17, 25, and 33, and once every 12 weeks thereafter until the end of second-line treatment; maximum time on treatment was 77 weeks. ] [ Designated as safety issue: No ]

    Objective response rate is defined as the percentage of participants with a best response of complete response or partial response based on investigator review of scans using modified RECIST criteria. A complete or partial response was confirmed no less than 4 weeks after the criteria for response were first met. Participants with no post-baseline radiographic tumor assessment(s) were considered non-responders.

    CR: disappearance of all target and non-target lesions and no new lesions. PR: At least a 30% decrease in the size of target lesions with no progression of non-target lesions (defined as a ≥ 25% increase in lesion size) and no new lesions, or, the disappearance of all target lesions but persistence of 1 or more non-target lesions not qualifying for either CR or PD and no new lesions.


  • Progression-free Survival Rate at Weeks 17 and 25 [ Time Frame: Week 17 and Week 25 ] [ Designated as safety issue: No ]

    The progression-free survival rate is defined as the Kaplan-Meier (KM) estimator of progression-free survival at Week 17 and Week 25 reported as the probability of being event (disease progression or death)-free. Tumor assessments were evaluated by the investigator according to modified RECIST criteria.

    PD: At least a 20% increase in the size of target lesions since the treatment started or at least a 25% increase in the size of non-target lesions and the lesion(s) measure ≥ 10 mm, or the appearance of any new lesions. Participants who withdraw from the study prior to completion of Week 17 or 25 radiographic tumor assessments were censored at the last evaluable tumor assessment.


  • Progression-free Survival Time [ Time Frame: From Study Day 1 until the data cut-off date of 2 January 2009; median follow-up time was 39 weeks, with a maximum of 93 weeks. ] [ Designated as safety issue: No ]
    Progression-free survival time was defined as the time from Study Day 1 to the date of disease progression (based on investigator assessment) or the date of death due to any cause. Participants who terminated from the study early (eg, prior to disease progression due to fully withdrawn informed consent) were censored at their last tumor assessment.

  • Disease Control Rate at Weeks 17 and 25 [ Time Frame: Week 17 and Week 25 ] [ Designated as safety issue: No ]
    The percentage of participants whose best response was either a complete or partial response or stable disease, based on modified RECIST criteria as assessed by the investigator. Stable diease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD of target lesions and no progression of existing non-target lesions and no new lesions, or, the persistence of 1 or more non-target lesions not qualifying for either CR or PD if no target lesions were identified at Baseline.

  • Duration of Response [ Time Frame: Tumor response was assessed at Weeks 9, 17, 25, and 33, and once every 12 weeks thereafter until the end of second-line treatment; maximum time on treatment was 77 weeks. ] [ Designated as safety issue: No ]
    Duration of response is defined as the time from the date of first response to the date of first progression of disease during second-line treatment (as evaluated by the investigator) or death (if the death was due to disease progression but not detected earlier) in the subset of participants who responded (CR or PR, as evaluated by the investigator). Duration of response was analyzed using Kaplan-Meier methods; participants who responded but did not progress while on study were censored at the date of last tumor assessment.

  • Overall Survival [ Time Frame: From Study Day 1 until the data cut-off date of 2 January 2009; median follow-up time was 39 weeks, with a maximum of 93 weeks. ] [ Designated as safety issue: No ]
    Overall survival is defined as as the number of days from Study Day 1 to the date of death due to any cause. Overall survival was analyzed using the Kaplan-Meier method; participants who were lost to follow-up or who had not died at the end of the study (52 weeks after the last participant was enrolled) were censored at the date of last contact.

  • Time to Treatment Failure [ Time Frame: Tumor response was assessed at Weeks 9, 17, 25, and 33, and once every 12 weeks thereafter until the end of second-line treatment; maximum time on treatment was 77 weeks. ] [ Designated as safety issue: No ]
    Time to failure of second-line treatment is defined as the time from study Day 1 to the date of the earliest of the following events: end of second-line therapy due to any reason except for complete response and curative surgery; progressive disease; or death due to any cause. Time to treatment failure was analyzed using Kaplan-Meier methods; participants who did not discontinue second-line treatment or discontinue due to complete response or curative surgery, who were still alive, and who did not have disease progression were censored at the date of the last contact.

  • Time to Progression [ Time Frame: From Study Day 1 until the data cut-off date of 2 January 2009; median follow-up time was 39 weeks, with a maximum of 93 weeks. ] [ Designated as safety issue: No ]
    Time to progression is defined as the time from study Day 1 to the date of observed disease progression. Time to progression was analyzed using Kaplan-Meier methods; participants who did not have disease progression were censored at the date of last evaluable tumor assessment.

  • Time to Response [ Time Frame: Tumor response was assessed at Weeks 9, 17, 25, and 33, and once every 12 weeks thereafter until the end of second-line treatment; maximum time on treatment was 77 weeks. ] [ Designated as safety issue: No ]
    Time to response of second-line treatment is defined as the time from study Day 1 to the date of first documentation of CR or PR, calculated for those participants with an objective tumor response of CR or PR.


Secondary Outcome Measures:
  • Number of Participants With Adverse Events [ Time Frame: From the first dose date to 30 days after the last dose date. The median time frame is 4.5 months. ] [ Designated as safety issue: No ]
    The severity of adverse events (AEs) was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, except for panitumumab related skin toxicities, where Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE; Grade 5 = Death related to AE. The relationship of each adverse event to the panitumumab and/or FOLFIRI regimen was assessed by the investigator. A serious adverse event was defined as an adverse event that • is fatal • is life threatening • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • is a congenital anomaly/birth defect • other significant medical hazard.

  • Number of Participants With Grade 4 Laboratory Toxicities [ Time Frame: From the first dose date to 30 days after the last dose date. The median time frame is 4.5 months. ] [ Designated as safety issue: No ]
    Laboratory toxicities were graded according to CTCAE version 3.

  • Number of Participants Who Developed Antibodies to Panitumumab [ Time Frame: Prior to first dose and 28 days after the last dose of second-line treatment ] [ Designated as safety issue: No ]
    The immunogenicity of panitumumab was evaluated using 2 different screening immunoassays for the detection of anti-panitumumab antibodies: an acid dissociation bridging enzyme-linked immunosorbent assay (ELISA; detecting high-affinity antibodies) and a Biacore® biosensor immunoassay (detecting both high and low-affinity antibodies). When either of the 2 screening assays yielded a positive result, that particular sample was subjected to an in vitro bioassay for the detection of neutralizing antibodies.


Enrollment: 116
Study Start Date: November 2006
Study Completion Date: October 2010
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Panitumumab plus FOLFIRI
Participants received 6 mg/kg panitumumab intravenously (IV) once every 14 days in combination with FOLFIRI chemotherapy regimen consisting of irinotecan, infusional 5-fluorouracil, and leucovorin, until disease progression, intolerability, death, or study withdrawal.
Biological: Panitumumab
Administered by intravenous infusion
Other Name: Vectibix
Drug: FOLFIRI
Chemotherapy consisting of irinotecan with infusional 5-fluorouracil and leucovorin. Recommended dosage regimen and administration of FOLFIRI was based on local standard of care, the package insert for each product, and institutional guidelines.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of metastatic adenocarcinoma of the colon or rectum
  • Available paraffin-embedded tumor tissue
  • Failure of first line treatment containing fluoropyrimidine and oxaliplatin based chemotherapy with bevacizumab for mCRC
  • Measurable disease
  • Adequate hematologic, renal, hepatic and metabolic function

Exclusion Criteria:

  • Radiotherapy ≤ 2 weeks prior to Day 1 of Cycle 1
  • Unresolved toxicity(ies) from prior anti cancer therapy that, in the opinion of the investigator, precludes the subject from study enrollment
  • Prior irinotecan therapy, anti epidermal growth factor receptor (EGFr) therapy, or vaccine for the treatment of mCRC
  • CYP3A4 enzyme inducers, inhibitors, and substrates (eg, phenytoin, phenobarbital, carbamazepine, ketoconazole, rifampin, rifabutin, and St. John's Wort) ≤ 2 weeks prior to Day 1 of Cycle 1
  • Infection requiring systemic anti infectives completed ≤ 2 weeks prior to Day 1 of Cycle 1
  • Clinically significant cardiovascular disease
  • History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis)
  • Pulmonary embolism, deep vein thrombosis, or other significant thromboembolic event ≤ 8 weeks prior to Day 1 of Cycle 1
  • Any significant bleeding ≤ 6 weeks prior to Day 1 of Cycle 1, per the investigator's judgement
  • Gastroduodenal ulcer(s) determined by endoscopy to be active or uncontrolled gastrointestinal ulcer ≤ 4 weeks prior to Day1 of Cycle 1
  • Any co-morbid disease or condition that could increase the risk of toxicity (eg, dihydropyrimidine deficiency, significant ascites, or pleural effusion)
  • Major surgery (requiring general anesthesia), open biopsy, or significant traumatic injury ≤ 4 weeks prior to Day1 of Cycle 1. Subjects must have recovered from surgery and have no significant complications
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00411450

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00411450     History of Changes
Other Study ID Numbers: 20060277 
Study First Received: December 12, 2006
Results First Received: January 15, 2016
Last Updated: January 15, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Amgen:
k-ras
biomarker
colorectal
colon
rectal
FOLFOX
FOLFIRI

Additional relevant MeSH terms:
Colorectal Neoplasms
Rectal Neoplasms
Neoplasm Metastasis
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 25, 2016