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Metastatic Colorectal CancerPhase 2STEPPNCT00332163

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

A Phase 2 study testing Panitumumab, Irinotecan and FOLFIRI in people with Metastatic Colorectal Cancer and Skin Rash, run by Amgen.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 90 years
What is being tested?
Panitumumab, Irinotecan and FOLFIRI
Could I receive a placebo?
No, everyone receives an active treatment
How many people
95 participants
Where
No sites listed yet
Study dates
Apr 2006to Sep 2008
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • Prior irinotecan use for the treatment of mCRC.

About this study

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

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.

Being tested
Panitumumab, Irinotecan, FOLFIRI, Pre-emptive Skin Treatment, Reactive Skin Treatment
Keywords
STEPP, STEP, STEEP, mCRC, Skin Toxicities, Skin Rash, Metastatic Colorectal Cancer, Anti-EGFr Skin Rash, colon cancer, colorectal cancer, rectal cancer
Medical subject headings
Colorectal Neoplasms, Exanthema, Colonic Neoplasms, Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PanitumumabBiological

    Also called Vectibix

    Administered by intravenous infusion

  • IrinotecanDrug

    Recommended dosage regimen and administration of irinotecan was based on local standard of care, the package insert, and institutional guidelines.

  • FOLFIRIDrug

    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.

  • Pre-emptive Skin TreatmentDrug

    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).

  • Reactive Skin TreatmentDrug

    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)

Study groups in NCT00332163
Study groupRoleWhat they receive
Pre-emptive Skin TreatmentExperimentalParticipants 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.
Receives: Biological: Panitumumab; Drug: Irinotecan; Drug: FOLFIRI; Drug: Pre-emptive Skin Treatment
Reactive Skin TreatmentExperimentalParticipants 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.
Receives: Biological: Panitumumab; Drug: Irinotecan; Drug: FOLFIRI; Drug: Reactive Skin Treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Specific Grade 2 or Higher Skin Toxicities During the 6-week Skin Treatment Period

    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.

    Measured: 6 weeks

Secondary outcomes (13)
  1. Percentage of Participants With Any Grade 2 or Higher Skin Toxicity of Any Type During the 6-week Skin Treatment Period

    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.

    Measured: 6 weeks

  2. Time to First Occurrence of Specific Grade 2 or Higher Skin Toxicities of Interest

    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.

    Measured: 6 weeks

  3. Most Severe Specific Grade 2 or Higher Skin Toxicities of Interest

    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.

    Measured: 6 weeks

  4. Time to First Most Severe Specific Grade 2 or Higher Skin Toxicities of Interest

    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.

    Measured: 6 weeks

  5. Percentage of Participants With Panitumumab Dose Reductions Due to the Specific Skin Toxicities of Interest

    Measured: 6 weeks

  6. Response Rate at First Scheduled Assessment

    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.

    Measured: 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.

  7. Best Overall Response Rate

    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.

    Measured: 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.

  8. Rate of Disease Control at First Scheduled Assessment

    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.

    Measured: 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.

  9. Time to Treatment Failure

    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.

    Measured: 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.

  10. Time to Progression

    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.

    Measured: 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.

  11. Overall Survival

    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.

    Measured: 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.

  12. Progression-free Survival

    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.

    Measured: 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.

  13. Change From Baseline in Overall Dermatologic Quality of Life Index (DLQI) Score

    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.

    Measured: Baseline and Weeks 2, 3, 4, 5, 6 and 7

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Jun 2006 (estimated)
  2. Study startApr 2006
  3. Primary completionJan 2008
  4. Study completionSep 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
95 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00332163
Sponsor's protocol ID
20050184
Acronym
STEPP
Status last verified
Jan 2016
First submitted
31 May 2006
Last updated
23 Feb 2016
Data monitoring committee
No

Publications

  • Lacouture ME, Mitchell EP, Piperdi B, Pillai MV, Shearer H, Iannotti N, Xu F, Yassine M. Skin toxicity evaluation protocol with panitumumab (STEPP), a phase II, open-label, randomized trial evaluating the impact of a pre-Emptive Skin treatment regimen on skin toxicities and quality of life in patients with metastatic colorectal cancer. J Clin Oncol. 2010 Mar 10;28(8):1351-7. doi: 10.1200/JCO.2008.21.7828. Epub 2010 Feb 8.

    PubMed 20142600
  • Weeraratne D, Chen A, Pennucci JJ, Wu CY, Zhang K, Wright J, Perez-Ruixo JJ, Yang BB, Kaliyaperumal A, Gupta S, Swanson SJ, Chirmule N, Starcevic M. Immunogenicity of panitumumab in combination chemotherapy clinical trials. BMC Clin Pharmacol. 2011 Nov 9;11:17. doi: 10.1186/1472-6904-11-17.

    PubMed 22070868
  • Mitchell EP, Piperdi B, Lacouture ME, Shearer H, Iannotti N, Pillai MV, Xu F, Yassine M. The efficacy and safety of panitumumab administered concomitantly with FOLFIRI or Irinotecan in second-line therapy for metastatic colorectal cancer: the secondary analysis from STEPP (Skin Toxicity Evaluation Protocol With Panitumumab) by KRAS status. Clin Colorectal Cancer. 2011 Dec;10(4):333-9. doi: 10.1016/j.clcc.2011.06.004. Epub 2011 Oct 14.

    PubMed 22000810

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Panitumumab, Irinotecan and FOLFIRI in people with Metastatic Colorectal Cancer and Skin Rash, run by Amgen.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Specific Grade 2 or Higher Skin Toxicities During the 6-week Skin Treatment Period (time frame: 6 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00332163, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2016.

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