search
Back to results

Safety and Efficacy Study for the Treatment of Non-Aggressive Basal Cell Carcinoma With Photodynamic Therapy

Primary Purpose

Basal Cell Carcinoma (BCC)

Status
Completed
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
BF-200 ALA
methyl-aminolevulinate
Sponsored by
Biofrontera Bioscience GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Basal Cell Carcinoma (BCC) focused on measuring Photodynamic Therapy, PDT, non-aggressive BCC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Main Inclusion Criteria:

  • Willing and able to sign informed consent form; obtained in writing before starting any study procedures
  • Presence of 1-3 thin (≤2 mm thickness), clinically non-aggressive, primary BCC lesions (primary superficial, nodular, or mixed superficial/nodular) in the face/forehead, bald scalp, extremities and/or neck/trunk. Confirmation of non-aggressiveness and thickness of BCC through biopsies taken at screening for at least one lesion. Lesions non-eligible according to biopsy should timely be removed by surgery or cryotherapy
  • Diameters of lesions should range between ≥0.5cm and ≤2cm; total maximal treated area is 10cm² (including 0.5-1.0cm margin surrounding each lesion)
  • Target BCC lesions must be discrete and quantifiable and have to be located within 1-2 treatment areas
  • Free of significant physical abnormalities (eg tattoos, dermatoses) in potential treatment area that may cause difficulty with examination or final evaluation
  • Accept to abstain from extensive sunbathing and use of solarium during observer blind part. Patients with sunburn within treatment areas cannot be included until fully recovered
  • Healthy patients and patients with clinically stable medical conditions, including, but not limited to controlled hypertension, diabetes mellitus type II, hypercholesterolemia, and osteoarthritis, will be permitted to be included in study if their medication is not prohibited by protocol
  • Women of childbearing potential are permitted to participate in study only if they have a negative serum pregnancy test at screening and willingness to use a highly effective method of contraception during observer blind part

Main Exclusion Criteria:

  • History of hypersensitivity to 5-ALA or any ingredient of BF-200 ALA, MAL or any ingredient of Metvix®, including arachis oil, or to peanut or soya
  • Hypersensitivity to porphyrins
  • Current treatment with immunosuppression therapy
  • Presence of porphyria
  • Presence of BCC lesions on embryonic fusion planes (H-zone)
  • Presence of more than 3 BCCs
  • Presence of malignant or benign tumors of the skin other than non-aggressive BCC within the treatment area (eg malignant melanoma, squamous cell carcinoma (SCC), aggressive BCC clinically diagnosed at screening) within the last 12 weeks
  • Gorlin Syndrome or Xeroderma pigmentosum
  • Presence of photodermatoses
  • Treatment of lesions (actinic keratosis (AK), BCC, SCC, Bowens disease, melanoma) ≤12 weeks prior to first PDT, except physical treatments (eg cryosurgery, excision surgery) that will not be allowed ≤6 weeks prior to first PDT (Visit 2). Lesion(s) that seemed eligible clinically which could not be confirmed by biopsy, and which are located ≥10cm to an eligible lesion should timely be removed physically only
  • Presence of inherited or acquired coagulation defect
  • Start of intake of medication with hypericin or systemically-acting drugs with phototoxic or photoallergic potential within 8 weeks prior to screening
  • Clinically relevant cardiovascular, hepatic, renal, neurologic, endocrine, or other major systemic disease making implementation of protocol or interpretation of study results difficult

  • Evidence of clinically significant (CS), unstable medical conditions, eg:

    • Metastatic tumor or tumor with high probability of metastasis
    • Cardiovascular disease (New York Heart Association [NYHA] class III, IV)
    • Immunosuppressive condition
    • Hematologic, hepatic, renal, neurologic, or endocrine condition
    • Collagen-vascular condition
    • Gastrointestinal condition
  • Topical treatment with 5-ALA or MAL outside treatment area during the observer blind part
  • Any topical treatment including diclofenac and immunomodulatory agents (eg imiquimod, ingenol mebutate) 12 weeks prior to first PDT session and during observer blind part
  • Any physical treatment during the observer blind part within treated target areas with exception of lesion(s) determined non-eligible by biopsy

Sites / Locations

  • Klinikum Vest GmbH

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

BF-200 ALA

methyl-aminolevulinate

Arm Description

Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and 0.5 to 1 cm of surrounding margin.

Topical application of Metvix creme containing 160 mg/g methyl-aminolevulinate. Application of a 1 mm thick layer covering each lesion and 0.5 to 1 cm of surrounding margin.

Outcomes

Primary Outcome Measures

Overall Patient Complete Response Rate Assessed 12 Weeks After the Last PDT
Overall patient complete response rate assessed 12 weeks after the last PDT. The indicated values give the percentage of overall complete responders. An overall complete responder is defined as a patient in whom all treated lesions were cleared. The PP set is the primary analysis set for the analyses of the primary endpoint.

Secondary Outcome Measures

Lesion Complete Response Assessed 12 Weeks After the Last PDT
Lesion complete response (completely cleared individual lesions) assessed 12 weeks after the last PDT. The indicated values give percentage of overall completely cleared individual lesions. The PP set is the primary analysis set for the analysis of the secondary endpoint.
Reduction of Lesion Area 12 Weeks After the Last PDT Compared to Baseline
Reduction of total lesion area (summation of sizes of all treated lesions) per patient, assessed 12 weeks after the last PDT. The PP set is the primary analysis set for the analysis of the secondary endpoint. Please note that the high SD for BF-200 ALA is due to a patient who had increased lesion area fom 63 mm² at baseline to 225 mm² 12 weeks after PDT. This lesion area included a lesion that was later confirmed to be benign skin condition (lentigo solaris).
Patient Complete Response 12 Weeks After PDT-2
Patient complete response (complete clearance of all treated lesions) assessed 12 weeks after PDT-2 (first PDT cycle). The PP set is the primary analysis set for the analysis of the secondary endpoint.
Cosmetic Outcome 12 Weeks After Last PDT (Including Patients With a Sum Score of 0 at Baseline)
Overall cosmetic outcome 12 weeks after last PDT is calculated as difference between 12 weeks after PDT sum score and baseline sum score of all skin quality assessments. Each of the below skin quality characteristics are assessed on a 4-point scale from 0 (none) to 3 (severe) by the investigator at baseline and 12 weeks after last PDT: Skin surface Hyperpigmentation Hypopigmentation Mottled or irregular pigmentation Degree of scarring Atrophy Cosmetic outcome categories are: Very good: 12 weeks sum score improved by at least 2 points compared to baseline Good: 12 weeks sum score improved by 1 point compared to baseline Satisfactory: 12 weeks sum score identical to the one at baseline Unsatisfactory: 12 weeks sum score worsened by 1 point compared to baseline Impaired: 12 weeks sum score worsened by at least 2 points compared to baseline
Cosmetic Outcome 12 Weeks After the Last PDT (Including Patients With a Baseline Sum Score >1)
Overall cosmetic outcome 12 weeks after last PDT is calculated as difference between 12 weeks after PDT sum score and baseline sum score of all skin quality assessments. Each of the below skin quality characteristics are assessed on a 4-point scale from 0 (none) to 3 (severe) by the investigator at baseline and 12 weeks after last PDT: Skin surface Hyperpigmentation Hypopigmentation Mottled or irregular pigmentation Degree of scarring Atrophy Cosmetic outcome categories are: Very good: 12 weeks sum score improved by at least 2 points compared to baseline Good: 12 weeks sum score improved by 1 point compared to baseline Satisfactory: 12 weeks sum score identical to the one at baseline Unsatisfactory: 12 weeks sum score worsened by 1 point compared to baseline Impaired: 12 weeks sum score worsened by at least 2 points compared to baseline

Full Information

First Posted
February 20, 2014
Last Updated
October 11, 2022
Sponsor
Biofrontera Bioscience GmbH
Collaborators
Accovion GmbH
search

1. Study Identification

Unique Protocol Identification Number
NCT02144077
Brief Title
Safety and Efficacy Study for the Treatment of Non-Aggressive Basal Cell Carcinoma With Photodynamic Therapy
Official Title
A Randomized, Observer Blind, Multinational Phase III Study to Evaluate the Safety and Efficacy of BF-200 ALA (Ameluz®) in Comparison to Metvix® in the Treatment of Non-aggressive Basal Cell Carcinoma (BCC) With Photodynamic Therapy (PDT)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
January 28, 2014 (Actual)
Primary Completion Date
November 17, 2015 (Actual)
Study Completion Date
September 9, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biofrontera Bioscience GmbH
Collaborators
Accovion GmbH

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The aim of this study is to test the effectiveness and safety of the medicine Ameluz® (5-aminolevulinic acid) in comparison to methyl-aminolevulinate (MAL), used with photodynamic therapy (PDT), to treat thin, non-aggressive BCC (basal cell carcinoma).
Detailed Description
The treatment comprises of up to 2 PDT cycles, each with two PDT sessions one week apart. If 12 weeks after the the second PDT all lesions are completely cleared the patient will enter the follow-up phase. In case of remaining lesions the patient will receive a second PDT cycle starting on the same day.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Basal Cell Carcinoma (BCC)
Keywords
Photodynamic Therapy, PDT, non-aggressive BCC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
InvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
281 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BF-200 ALA
Arm Type
Active Comparator
Arm Description
Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and 0.5 to 1 cm of surrounding margin.
Arm Title
methyl-aminolevulinate
Arm Type
Active Comparator
Arm Description
Topical application of Metvix creme containing 160 mg/g methyl-aminolevulinate. Application of a 1 mm thick layer covering each lesion and 0.5 to 1 cm of surrounding margin.
Intervention Type
Drug
Intervention Name(s)
BF-200 ALA
Other Intervention Name(s)
Ameluz
Intervention Description
Topical treatment for photodynamic therapy combining drug application and subsequent illumination with a narrow spectrum light source (after 3 h of drug incubation)
Intervention Type
Drug
Intervention Name(s)
methyl-aminolevulinate
Other Intervention Name(s)
Metvix / Metvixia
Intervention Description
Topical treatment for photodynamic therapy combining drug application and subsequent illumination with a narrow spectrum light source (after 3 h of drug incubation)
Primary Outcome Measure Information:
Title
Overall Patient Complete Response Rate Assessed 12 Weeks After the Last PDT
Description
Overall patient complete response rate assessed 12 weeks after the last PDT. The indicated values give the percentage of overall complete responders. An overall complete responder is defined as a patient in whom all treated lesions were cleared. The PP set is the primary analysis set for the analyses of the primary endpoint.
Time Frame
12 weeks after the last PDT (please note: 2 PDT cycles, each cycle consisting of 2 PDTs (= maximum of 4 PDTs per patient) was possible).
Secondary Outcome Measure Information:
Title
Lesion Complete Response Assessed 12 Weeks After the Last PDT
Description
Lesion complete response (completely cleared individual lesions) assessed 12 weeks after the last PDT. The indicated values give percentage of overall completely cleared individual lesions. The PP set is the primary analysis set for the analysis of the secondary endpoint.
Time Frame
12 weeks after the last PDT (please note: 2 PDT cycles, each cycle consisting of 2 PDTs (= maximum of 4 PDTs per patient) was possible).
Title
Reduction of Lesion Area 12 Weeks After the Last PDT Compared to Baseline
Description
Reduction of total lesion area (summation of sizes of all treated lesions) per patient, assessed 12 weeks after the last PDT. The PP set is the primary analysis set for the analysis of the secondary endpoint. Please note that the high SD for BF-200 ALA is due to a patient who had increased lesion area fom 63 mm² at baseline to 225 mm² 12 weeks after PDT. This lesion area included a lesion that was later confirmed to be benign skin condition (lentigo solaris).
Time Frame
12 weeks after the last PDT (please note: 2 PDT cycles, each cycle consisting of 2 PDTs (= maximum of 4 PDTs per patient) was possible).
Title
Patient Complete Response 12 Weeks After PDT-2
Description
Patient complete response (complete clearance of all treated lesions) assessed 12 weeks after PDT-2 (first PDT cycle). The PP set is the primary analysis set for the analysis of the secondary endpoint.
Time Frame
12 weeks after PDT-2 (=PDT cycle 1; please note: in this study 2 PDT cycles, each cycle consisting of 2 PDTs (= maximum of 4 PDTs per patient) was possible).
Title
Cosmetic Outcome 12 Weeks After Last PDT (Including Patients With a Sum Score of 0 at Baseline)
Description
Overall cosmetic outcome 12 weeks after last PDT is calculated as difference between 12 weeks after PDT sum score and baseline sum score of all skin quality assessments. Each of the below skin quality characteristics are assessed on a 4-point scale from 0 (none) to 3 (severe) by the investigator at baseline and 12 weeks after last PDT: Skin surface Hyperpigmentation Hypopigmentation Mottled or irregular pigmentation Degree of scarring Atrophy Cosmetic outcome categories are: Very good: 12 weeks sum score improved by at least 2 points compared to baseline Good: 12 weeks sum score improved by 1 point compared to baseline Satisfactory: 12 weeks sum score identical to the one at baseline Unsatisfactory: 12 weeks sum score worsened by 1 point compared to baseline Impaired: 12 weeks sum score worsened by at least 2 points compared to baseline
Time Frame
12 weeks after the last PDT (please note: 2 PDT cycles, each cycle consisting of 2 PDTs (= maximum of 4 PDTs per patient) was possible).
Title
Cosmetic Outcome 12 Weeks After the Last PDT (Including Patients With a Baseline Sum Score >1)
Description
Overall cosmetic outcome 12 weeks after last PDT is calculated as difference between 12 weeks after PDT sum score and baseline sum score of all skin quality assessments. Each of the below skin quality characteristics are assessed on a 4-point scale from 0 (none) to 3 (severe) by the investigator at baseline and 12 weeks after last PDT: Skin surface Hyperpigmentation Hypopigmentation Mottled or irregular pigmentation Degree of scarring Atrophy Cosmetic outcome categories are: Very good: 12 weeks sum score improved by at least 2 points compared to baseline Good: 12 weeks sum score improved by 1 point compared to baseline Satisfactory: 12 weeks sum score identical to the one at baseline Unsatisfactory: 12 weeks sum score worsened by 1 point compared to baseline Impaired: 12 weeks sum score worsened by at least 2 points compared to baseline
Time Frame
12 weeks after the last PDT (please note: 2 PDT cycles, each cycle consisting of 2 PDTs (= maximum of 4 PDTs per patient) was possible).
Other Pre-specified Outcome Measures:
Title
Patient Recurrence Rate (Overall, Cumulative)
Description
Patient recurrence rate defined as the number of patients with at least one recurrent lesion during FU after complete clearance 12 weeks after the last PDT
Time Frame
6, 12, 24, 36 and 60 months post-PDT
Title
Lesion Recurrence Rate (Cumulative)
Description
Lesion recurrence rate defined as the number of completely cleared lesions 12 weeks after the last PDT showing recurrence during FU. Overall and subgroup analysis (nodular basal cell carcinoma (nBCC) and superficial basal cell carcinoma (sBCC)).
Time Frame
6, 12, 24, 36 and 60 months post-PDT

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Main Inclusion Criteria: Willing and able to sign informed consent form; obtained in writing before starting any study procedures Presence of 1-3 thin (≤2 mm thickness), clinically non-aggressive, primary BCC lesions (primary superficial, nodular, or mixed superficial/nodular) in the face/forehead, bald scalp, extremities and/or neck/trunk. Confirmation of non-aggressiveness and thickness of BCC through biopsies taken at screening for at least one lesion. Lesions non-eligible according to biopsy should timely be removed by surgery or cryotherapy Diameters of lesions should range between ≥0.5cm and ≤2cm; total maximal treated area is 10cm² (including 0.5-1.0cm margin surrounding each lesion) Target BCC lesions must be discrete and quantifiable and have to be located within 1-2 treatment areas Free of significant physical abnormalities (eg tattoos, dermatoses) in potential treatment area that may cause difficulty with examination or final evaluation Accept to abstain from extensive sunbathing and use of solarium during observer blind part. Patients with sunburn within treatment areas cannot be included until fully recovered Healthy patients and patients with clinically stable medical conditions, including, but not limited to controlled hypertension, diabetes mellitus type II, hypercholesterolemia, and osteoarthritis, will be permitted to be included in study if their medication is not prohibited by protocol Women of childbearing potential are permitted to participate in study only if they have a negative serum pregnancy test at screening and willingness to use a highly effective method of contraception during observer blind part Main Exclusion Criteria: History of hypersensitivity to 5-ALA or any ingredient of BF-200 ALA, MAL or any ingredient of Metvix®, including arachis oil, or to peanut or soya Hypersensitivity to porphyrins Current treatment with immunosuppression therapy Presence of porphyria Presence of BCC lesions on embryonic fusion planes (H-zone) Presence of more than 3 BCCs Presence of malignant or benign tumors of the skin other than non-aggressive BCC within the treatment area (eg malignant melanoma, squamous cell carcinoma (SCC), aggressive BCC clinically diagnosed at screening) within the last 12 weeks Gorlin Syndrome or Xeroderma pigmentosum Presence of photodermatoses Treatment of lesions (actinic keratosis (AK), BCC, SCC, Bowens disease, melanoma) ≤12 weeks prior to first PDT, except physical treatments (eg cryosurgery, excision surgery) that will not be allowed ≤6 weeks prior to first PDT (Visit 2). Lesion(s) that seemed eligible clinically which could not be confirmed by biopsy, and which are located ≥10cm to an eligible lesion should timely be removed physically only Presence of inherited or acquired coagulation defect Start of intake of medication with hypericin or systemically-acting drugs with phototoxic or photoallergic potential within 8 weeks prior to screening Clinically relevant cardiovascular, hepatic, renal, neurologic, endocrine, or other major systemic disease making implementation of protocol or interpretation of study results difficult Evidence of clinically significant (CS), unstable medical conditions, eg: Metastatic tumor or tumor with high probability of metastasis Cardiovascular disease (New York Heart Association [NYHA] class III, IV) Immunosuppressive condition Hematologic, hepatic, renal, neurologic, or endocrine condition Collagen-vascular condition Gastrointestinal condition Topical treatment with 5-ALA or MAL outside treatment area during the observer blind part Any topical treatment including diclofenac and immunomodulatory agents (eg imiquimod, ingenol mebutate) 12 weeks prior to first PDT session and during observer blind part Any physical treatment during the observer blind part within treated target areas with exception of lesion(s) determined non-eligible by biopsy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rolf M. Szeimies, Prof. Dr.
Organizational Affiliation
Klinik fuer Dermatologie und Allergologie (Klinikum Vest - Knappschaftskrankenhaus), Recklinghausen, Germany
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Colin Morton, Dr.
Organizational Affiliation
Dermatology Department, Stirling Community Hospital, NHS Forth Valley, United Kingdom
Official's Role
Principal Investigator
Facility Information:
Facility Name
Klinikum Vest GmbH
City
Recklinghausen
State/Province
Westfalen-Lippe
ZIP/Postal Code
45657
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
29432644
Citation
Morton CA, Dominicus R, Radny P, Dirschka T, Hauschild A, Reinhold U, Aschoff R, Ulrich M, Keohane S, Ekanayake-Bohlig S, Ibbotson S, Ostendorf R, Berking C, Grone D, Schulze HJ, Ockenfels HM, Jasnoch V, Kurzen H, Sebastian M, Stege H, Staubach P, Gupta G, Hubinger F, Ziabreva I, Schmitz B, Gertzmann A, Lubbert H, Szeimies RM. A randomized, multinational, noninferiority, phase III trial to evaluate the safety and efficacy of BF-200 aminolaevulinic acid gel vs. methyl aminolaevulinate cream in the treatment of nonaggressive basal cell carcinoma with photodynamic therapy. Br J Dermatol. 2018 Aug;179(2):309-319. doi: 10.1111/bjd.16441. Epub 2018 May 16.
Results Reference
result
Links:
URL
http://www.ncbi.nlm.nih.gov/pubmed/29432644
Description
US National Library of Medicine National Institutes of Health

Learn more about this trial

Safety and Efficacy Study for the Treatment of Non-Aggressive Basal Cell Carcinoma With Photodynamic Therapy

We'll reach out to this number within 24 hrs