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Skin Toxicity Treatment in Metastatic Colorectal Cancer (mCRC) Patients Receiving Panitumumab + Irinotecan-based Therapy (STEPP)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00332163
First received: May 31, 2006
Last updated: January 26, 2016
Last verified: January 2016
  Purpose
A comparison of prophylactic treatment with reactive treatment for skin toxicity observed in patients with metastatic colorectal cancer (mCRC) who are receiving second-line irinotecan-based chemotherapy concomitantly with panitumumab.

Condition Intervention Phase
Metastatic Colorectal Cancer
Skin Rash
Skin Toxicities
Colon Cancer
Colorectal Cancer
Biological: Panitumumab
Drug: Irinotecan
Drug: FOLFIRI
Drug: Pre-emptive Skin Treatment
Drug: Reactive Skin Treatment
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Open-label, Randomized Clinical Trial of Skin Toxicity Treatment in Subjects Receiving Second-line FOLFIRI or Irinotecan Only Chemotherapy Concomitantly With Panitumumab

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Percentage of Participants With Specific Grade 2 or Higher Skin Toxicities During the 6-week Skin Treatment Period [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Skin toxicities were assessed by the study clinician and graded according to the modified Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0 Dermatology Toxicity Grading criteria, on a scale from Grade 1 (mild) to 4 (life-threatening). The specific skin toxicities of interest were pruritus, acneiform dermatitis, skin desquamation (also described as skin exfoliation), exfoliative dermatitis, paronychia, nail disorder, skin fissures, skin laceration, pruritic rash, pustular rash, skin infection, skin ulceration, and local infection.


Secondary Outcome Measures:
  • Percentage of Participants With Any Grade 2 or Higher Skin Toxicity of Any Type During the 6-week Skin Treatment Period [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    The percentage of participants who developed at least 1 incidence of ≥ grade 2 skin toxicities of any type during the 6-week skin treatment period. Analysis of this endpoint was based on adverse event data associated with the "Skin and Subcutaneous Tissue Disorders" system organ class. Adverse events were graded according to the National Cancer Institute (NCI) CTCAE version 3.0.

  • Time to First Occurrence of Specific Grade 2 or Higher Skin Toxicities of Interest [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    The time to the first occurrence of specific grade 2 or higher skin toxicities of interest was defined as the time from the first dose of panitumumab to the date of first occurrence of specific ≥ grade 2 skin toxicities of interest. Participants who did not experience specific skin-related toxicities were censored at their last skin toxicity assessment during the skin toxicity assessment period. Skin toxicities were assessed by the study clinician and graded according to the modified CTCAE v.3.0 Dermatology Toxicity Grading criteria, on a scale from Grade 1 (mild) to 4 (life-threatening). The specific skin toxicities of interest were pruritus, acneiform dermatitis, skin desquamation (also described as skin exfoliation), exfoliative dermatitis, paronychia, nail disorder, skin fissures, skin laceration, pruritic rash, pustular rash, skin infection, skin ulceration, and local infection.

  • Most Severe Specific Grade 2 or Higher Skin Toxicities of Interest [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    The percentage of participants with a most severe grade of 2, 3 or 4 specific skin toxicity of interest reported during the 6-week skin treatment period. Skin toxicities were assessed by the study clinician and graded according to the modified CTCAE v.3.0 Dermatology Toxicity Grading criteria, on a scale from Grade 1 (mild) to 4 (life-threatening). The specific skin toxicities of interest were pruritus, acneiform dermatitis, skin desquamation (also described as skin exfoliation), exfoliative dermatitis, paronychia, nail disorder, skin fissures, skin laceration, pruritic rash, pustular rash, skin infection, skin ulceration, and local infection.

  • Time to First Most Severe Specific Grade 2 or Higher Skin Toxicities of Interest [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Time to the first most severe grade ≥ 2 of all the specific skin-related toxicities of interest was defined as the time from the first dose of panitumumab to the date of the first occurrence of the most severe specific ≥ grade 2 skin toxicity of interest during the 6-week skin treatment period. Participants who did not experience any specific skin-related toxicity of grade ≥ 2 were censored at their last skin toxicity assessment during the 6-week skin toxicity assessment period. Skin toxicities were assessed by the study clinician and graded according to the modified CTCAE v.3.0 Dermatology Toxicity Grading criteria, on a scale from Grade 1 (mild) to 4 (life-threatening). The specific skin toxicities of interest were pruritus, acneiform dermatitis, skin desquamation (also described as skin exfoliation), exfoliative dermatitis, paronychia, nail disorder, skin fissures, skin laceration, pruritic rash, pustular rash, skin infection, skin ulceration, and local infection.

  • Percentage of Participants With Panitumumab Dose Reductions Due to the Specific Skin Toxicities of Interest [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Response Rate at First Scheduled Assessment [ Time Frame: Week 9 with confirmed response at Week 13 for the FOLFIRI and panitumumab Q2W regimen or at Week 10 with confirmed response at Week 14 for the irinotecan and panitumumab Q3W regimen. ] [ Designated as safety issue: No ]
    Tumor response was assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI) of the abdomen, pelvis, and all other sites of disease. Disease assessments were performed by central review according to the modified response evaluation criteria in solid tumors (RECIST). Response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) at the Week 9/10 assessment visit and a corresponding CR or PR confirmed at the Week 13/14 assessment visit for the Q2W/Q3W regimens. CR: Disappearance of all target and non-target lesions and no new lesions. PR: Either the disappearance of all target lesions with persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease (PD; ≥ 25% increase in lesion size) and no new lesions, or, at least a 30% decrease in the size of target lesions with no progression of existing non-target lesions, and no new lesions.

  • Best Overall Response Rate [ Time Frame: Response was assessed at Weeks 9 and 13 and then every 8 weeks for the Q2W regimen, or at Weeks 10, 14, 22 and then every 9 weeks for the Q3W regimen until the end of treatment; median treatment duration was 13 and 17 weeks in each group respectively. ] [ Designated as safety issue: No ]
    Best overall response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) while on study. Tumor response was assessed by CT scan or MRI of the abdomen, pelvis, and all other sites of disease. Disease assessments were performed by central review according to the modified RECIST criteria. CR: Disappearance of all target and non-target lesions and no new lesions. PR: Either the disappearance of all target lesions with persistence of one or more non-target lesion(s) not qualifying for either CR or PD (≥ 25% increase in lesion size) and no new lesions, or, at least a 30% decrease in the size of target lesions with no progression of existing non-target lesions, and no new lesions.

  • Rate of Disease Control at First Scheduled Assessment [ Time Frame: Week 9 with confirmed response at Week 13 for the FOLFIRI and panitumumab Q2W regimen or at Week 10 with confirmed response at Week 14 for the irinotecan and panitumumab Q3W regimen. ] [ Designated as safety issue: No ]
    Tumor response was assessed by CT scan or MRI of the abdomen, pelvis, and all other sites of disease. Disease assessments were performed by central review according to the modified response evaluation criteria in solid tumors (RECIST). Disease control rate is defined as the percentage of participants with a CR, PR or stable disease (SD) at the Week 9/10 assessment visit and a corresponding response (CR or PR) confirmed at the Week 13/14 assessment visit for the Q2W/Q3W regimens. SD: Neither sufficient shrinkage or increase in target lesions to qualify for PR or PD, with no progression of non-target lesions and no new lesions.

  • Time to Treatment Failure [ Time Frame: From randomization until the end of study; median time on study was 31 weeks and 41 weeks in each treatment group respectively with a maximum time on study of 97 weeks. ] [ Designated as safety issue: No ]
    Time-to-treatment failure is defined as the time from the date of randomization to the first date of any of the following events: discontinuation of study therapy due to any reason (except for complete response and curative surgery), progression of disease, or death due to any cause. Participants who did not discontinue, who were still alive, and who did not have disease progression were censored at the date of last contact. Time to treatment failure was analyzed using the Kaplan-Meier method.

  • Time to Progression [ Time Frame: From randomization until the end of study; median time on study was 31 weeks and 41 weeks in each treatment group respectively with a maximum time on study of 97 weeks. ] [ Designated as safety issue: No ]

    Time from the date of randomization to the date of observed disease progression or death due to disease progression. Participants who did not have documented disease progression were censored at the date of last tumor assessment; participants who died for reasons other than disease progression while on study were censored at the date of death. PD: At least a 20% increase in the size of target lesions, recorded since the treatment started, or at least a 25% increase in size of non-target lesions and the lesion(s) measure > 10 mm in one dimension, or the appearance of one or more new lesions.

    Time to progression was analyzed using the Kaplan-Meier method. This analysis excludes any data collected during follow-up for participants who began third-line treatment.


  • Overall Survival [ Time Frame: From randomization until the end of study; median time on study was 31 weeks and 41 weeks in each treatment group respectively with a maximum time on study of 97 weeks. ] [ Designated as safety issue: No ]
    Overall Survival is defined as the time from the date of randomization to the date of death. Participants who did not die while on study or who were lost-to-follow-up were censored at their last contact date. Overall survival was analyzed using all data regardless of whether it was collected during second- or third-line treatment.

  • Progression-free Survival [ Time Frame: From randomization until the end of study; median time on study was 31 weeks and 41 weeks in each treatment group respectively with a maximum time on study of 97 weeks. ] [ Designated as safety issue: No ]
    Defined as the time from the date of randomization to the first date of observed disease progression or death due to any cause (whichever comes first). Participants who were alive and had not progressed while on study were censored at the date of last progression-free tumor assessment.

  • Change From Baseline in Overall Dermatologic Quality of Life Index (DLQI) Score [ Time Frame: Baseline and Weeks 2, 3, 4, 5, 6 and 7 ] [ Designated as safety issue: No ]
    Skin-related quality of life was assessed using the DLQI. The DLQI questionnaire asks participants to evaluate the degree that their skin condition has affected their quality of life in the last week. Participants answer 10 questions on a scale from 0 (not at all) to 3 (very much); The DLQI score is calculated by summing the scores for all questions, resulting in a maximum of 30 and a minimum of 0; higher scores indicate a more impaired quality of life.


Enrollment: 95
Study Start Date: April 2006
Study Completion Date: September 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pre-emptive Skin Treatment
Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy.
Biological: Panitumumab
Administered by intravenous infusion
Other Name: Vectibix
Drug: Irinotecan
Recommended dosage regimen and administration of irinotecan was based on local standard of care, the package insert, and institutional guidelines.
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.
Drug: Pre-emptive Skin Treatment
Pre-emptive skin treatment included a skin moisturizer (eg, Lubriderm), sunscreen (free of paraaminobenzoic acid (PABA), skin protection factor (SPF) 15 or higher, ultraviolet-A (UV-A), and UV-B protection), topical steroid (1% hydrocortisone cream) and oral antibiotic (doxycycline, 100 mg twice daily).
Experimental: Reactive Skin Treatment
Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required.
Biological: Panitumumab
Administered by intravenous infusion
Other Name: Vectibix
Drug: Irinotecan
Recommended dosage regimen and administration of irinotecan was based on local standard of care, the package insert, and institutional guidelines.
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.
Drug: Reactive Skin Treatment
Treatment was based on symptoms and severity and may have included an emollient (eg, Lubriderm, Vaseline), sunscreen (SPF ≥ 15), oral antibiotic (eg, doxycycline, ciprofloxacin, cefadroxil, amoxicillin/clavulanic acid), topical steroid (hydrocortisone cream), topical antibiotic (clindamycin), oral systemic steroid, topical medical treatment (eg, silver sulfadiazine, Silvadene), topical antihistamine or oral antihistamine (hydroxyzine)

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with unresectable metastatic adenocarcinoma of the colon or rectum that cannot, in the opinion of the investigator, be cured by surgical resection at the time of randomization;
  • Patients who have failed first line treatment containing fluoropyrimidine and oxaliplatin based chemotherapy with or without bevacizumab for mCRC.

Exclusion Criteria:

• Prior irinotecan use for the treatment of mCRC.

  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: NCT00332163

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: NCT00332163     History of Changes
Other Study ID Numbers: 20050184 
Study First Received: May 31, 2006
Results First Received: January 12, 2016
Last Updated: January 26, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Amgen:
STEPP
STEP
STEEP
mCRC
Skin Toxicities
Skin Rash
Metastatic Colorectal Cancer
Anti-EGFr Skin Rash
colon cancer
colorectal cancer
rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Neoplasms
Exanthema
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Skin Diseases
Irinotecan
Camptothecin
Anti-Bacterial Agents
Antibiotics, Antitubercular
Hydrocortisone 17-butyrate 21-propionate
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone
Antibodies, Monoclonal
Sunscreening Agents
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 05, 2016