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Study Summary
No. 2008-0826:.......Skin......Madeleine Duvic......Dermatology
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Study Summary Title
Study Summary
Number:
2008-0826
Study Title:A Phase 1, Multi-center, Randomized, Double-Blind, Sequential,
Placebo Controlled Study of the Safety, Tolerability, and Systemic
Absorption of Menadione Topical Lotion as an Emergent and Preemergent
Treatment for Epidermal-Growth-Factor-Receptor (EGFR)
Inhibitor-Associated Rash
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Physician New Patient Referral
Name:Madeleine DuvicPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:DermatologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-4578
Contact us about clinical trials
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General Information
Disease Group:SkinSupported By:HanaBiosciences
Phase of Study:Phase IReturn
Visit:
Grp 1, 10 Visits plus Extended Treatment ( Extended Treatment Period 1 (Visits
9.1 - 9.2, if applicable); Grp 2, 9 Visits plus Extended Treatment (Visits 9.2
-9.3 if applicable); Early Termination Visit is applicable to all subjects
Treatment
Agents:
Menadione Top. Lot 0.05%
Menadione Top. Lot 0.1%
Menadione Top. Lot. 0.2%
Home Care:n/a
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
n/a
Description/
Intervention:
The goal of this clinical research study is to learn about the safety and
tolerability of giving menadione lotion to patients who will receive a certain
type of cancer treatment that commonly causes skin rash. Researchers want to
learn if menadione lotion can help to prevent the skin rash.
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Study Objectives / Outcomes
Primary Objectives
  • To evaluate the safety and tolerability of twice-daily, topical menadione lotion to one side of the face, anterior neck, and upper chest in subjects with new onset EGFR inhibitor-induced rash (treatment emergent group) and those about to begin EGFR inhibitor therapy who are at risk for the rash (treatment pre-emergent). Evaluation of safety and tolerability will be performed through the PK profile assessments.
  • To evaluate the systemic absorption and bioavailability of topically applied menadione lotion in subjects with new onset EGFR inhibitor-induced rash (disrupted skin) and those about to begin EGFR inhibitor therapy who are at risk for the rash (intact skin)

Secondary Objectives
  • To evaluate the skin rash status during study drug administration to one side of the face, anterior neck, and upper chest in subjects with new onset EGFR inhibitor induced rash (treatment emergent group) and those about to begin EGFR inhibitor therapy who are at risk for the rash (treatment pre-emergent)
  • To evaluate the tumor response to EGFR inhibitor therapy during and following topical menadione administration
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Study Status Information
Study Activation / Registration Date:08/07/2009
IRB Review and Approval Date:08/07/2009
Study Type:Phase I
Recruitment Status:Closed
Projected Accrual:24
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Male or female subjects at least 18 years old.

2) Have been prescribed an approved EGFRI to treat cancer and expect to begin this treatment within 14 days (i.e., any EGFRI that is approved for the treatment of cancer at the time of subject enrollment).

3) For Group 1: Agree to return to clinic at Visit 3 or at first acute signs and symptoms of rash (papular and/or pustular eruptions and/or nodules) on the face/neck and/or upper chest that is suspected of being related to the EGFRI therapy within 21 days of starting EGFRI therapy. For Group 2: Expect to start EGFRI therapy one day after starting treatment with study lotion.

4) Have an Eastern Co-operative Oncology Group (ECOG) performance rating </= 2.

5) Have a life expectancy of at least 4 months.

6) Males or non-pregnant, non-lactating females who are postmenopausal, naturally or surgically sterile, or who agree to use effective contraceptive methods throughout the course of the study. Postmenopausal is defined as at least 12 months natural spontaneous amenorrhea, or at least 6 weeks following surgical menopause (bilateral oophorectomy).

7) Females of childbearing potential and males with female sexual partners of childbearing potential must agree to use one of the following acceptable birth control methods: a.) Surgically sterile (hysterectomy or bilateral oophorectomy); b.) Surgically sterile (bilateral tubal ligation with surgery at least 6 weeks prior to study initiation). Documentation is required; c.) Intrauterine device in place for at least 3 months; d.) Double-barrier method (condom and diaphragm) with spermicide for at least 14 days prior to screening and through study completion [continues in eligibility #8]

8) [continued from eligibility #7] e.) Stable hormonal contraceptive (oral, topical, vaginal or implanted/injected) for at least 3 months prior to study and through study completion; f. Abstinence; g.) Single-barrier method for at least 14 days prior to screening and through study completion for vasectomized males or females with vasectomized partners.

9) Able to understand and provide signed informed consent.

10) Females of childbearing potential must have a negative serum beta-hCG pregnancy test at Visit 1 and negative urine beta-hCG pregnancy test at Visit 3 (Group 1) or Visit 2 (Group 2).

Exclusion Criteria:1) A skin examination reveals the presence of any active disease (e.g., eczema), tattoos or other problems, such as open lesions, that could make that application site unacceptable for study drug lotion application, located on the face/neck and/or upper chest that, in the Investigator's opinion, could confound the evaluation of the rash.

2) Any clinically significant safety laboratory or diagnostic results that, in the opinion of the Investigator, would place the subject at undue risk if the subject were to participate in the study.

3) Any clinically significant finding or concurrent clinical illness in the physical examination or medical history that, in the opinion of the Investigator, would place the subject at undue risk if the subject were to participate in the study.

4) Undergoing any current treatment for cancer other than the prescribed EGFRI that in the opinion of the Investigator, would place the subject at undue risk if the subject were to participate in the study.

5) Prior treatment with any marketed or investigational EGFRI therapy within the 3 months prior to screening (Visit 1).

6) Treatment with topical antibiotics, topical steroids, and other topical treatments on the face/neck and/or upper chest within 14 days of first study lotion application.

7) Systemic use of steroids will be stopped at Visit 1 and not allowed during the course of the study.

8) Treatment with vitamin K supplements or multivitamins containing any form of vitamin K should be stopped at Visit 1.

9) Known hypersensitivity to menadione or similar compounds including any of the inactive ingredients

10) Treatment with oral anticoagulants (i.e., Warfarin).

11) Any subjects with prior history of bleeding and hemolytic disorders.

12) Clinically significant abnormal laboratory values at screening, to include but not limited to the following hematologic, renal and liver function laboratory values: a). Hematologic function: Hgb < 9.0 g/dL or < 10.0 g/dL for subjects receiving hematopoietic growth factors, such as darbopoeitin alfa or epoetin alfa, ANC < 500/mm3 (or < 1.5 x 10^9/L), Platelet count < 100,000/mm3 (or < 100 × 10^9/L);[continues in exclusion #13]

13) [Continued from eligibility #12] - b.) Renal function: Serum creatinine > 1.5 mg/dL or > 133 umol/L (SI units) or calculated estimated creatinine clearance < 60 mL/min/1.73 m^2 based on Cockcroft and Gault formula; c.) Hepatic function: Aspartate transaminase (AST) or alanine transaminase (ALT) > 3 x institutional ULN or > 5 X institutional ULN if documented liver metastasis, Total bilirubin > 2 X institutional ULN or > 5 X institutional ULN if documented liver metastasis.

14) Treatment with any cosmetic cream, make-up or products such as sunscreen, oils, powders, perfumes, lotions, ointments, etc. to the anticipated study drug lotion application area within 3 days before treatment or during the treatment period.

15) Known or suspected pregnancy, lactation or planned pregnancy (females and males).

16) Clinically significant mental illness (to be determined by the Investigator).

17) Exposure to any investigational agent within 2 weeks or 3 half lives prior to randomization (Visit 3, Day 1 for Group 1 or Visit 2, Day 1 for Group 2)

18) The subject will be disqualified if they have a rash for longer than 5 days at a grade of 3 or more prior to administration of first menadione dose (per CTCAE v3.0 terminology).

19) Subject has a condition the Investigator believes would interfere with the ability to provide informed consent or comply with study instructions, or that might confound the interpretation of the study results or put the subject at undue risk.

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Links
Registration Number: NCT00656786
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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