A Randomized Phase 3 Study of Tasisulam Administered as an Intravenous Infusion on Day 1 of a 28-Day Cycle vs. Paclitaxel as Second-Line Treatment in Patients with Metastatic Melanoma

• Register: EUCTR
• Last refreshed on: 7 August 2012
• Main ID: EUCTR2009-014591-21-AT
• Date of registration: 10/12/2009
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company
• Public title: A Randomized Phase 3 Study of Tasisulam Administered as an Intravenous Infusion on Day 1 of a 28-Day Cycle vs. Paclitaxel as Second-Line Treatment in Patients with Metastatic Melanoma
• Scientific title: A Randomized Phase 3 Study of Tasisulam Administered as an Intravenous Infusion on Day 1 of a 28-Day Cycle vs. Paclitaxel as Second-Line Treatment in Patients with Metastatic Melanoma
• Date of first enrolment: 24/03/2010
• Target sample size: 800
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-014591-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Austria, Belgium, Finland, France, Germany, Italy, Netherlands, Poland, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
[1] Have a histologic and/or cytologic diagnosis of metastatic melanoma
(Stage IV).
[2] Have the presence of evaluable disease as defined by the Response
Evaluation Criteria in Solid Tumors (RECIST version1.0).
[3] Are at least 18 years of age.
[4] Have a performance status of 0 to 1 on the Eastern Cooperative
Oncology Group (ECOG) Scale (see Attachment JZAO.4).
[5] Have progressed after 1 previous systemic treatment regimen
containing dacarbazine or temozolomide for metastatic melanoma.
[6] Have discontinued all previous therapies for cancer, including
chemotherapy, radiotherapy, immunotherapy, or other investigational
therapy for at least 30 days (45 days for mitomycin-C or nitrosoureas)
before study enrollment and recovered from the acute effects of
therapy (except alopecia). Whole-brain radiation must have been
completed 90 days before starting study therapy.
[7] Have adequate organ function including:
• Bone Marrow Reserve: Absolute neutrophil count (ANC)
= 1.5 x 109/L prior to treatment, platelets = 100 x 109/L, and
hemoglobin = 8 g/dL (transfusions are not allowed to reach 8 g/dL
prior to enrollment).
• Hepatic: Bilirubin = 1.5 times the upper limit of normal (ULN).
Alkaline phosphatase and transaminases (ALT and AST) =5 times
ULN.
• Renal: Serum creatinine at or below the ULN. No known active
renal disease.
[8] Have a serum albumin level = 3.0 g/dL or = 30 g/L.
[9] Males and females with reproductive potential should use medically
approved contraceptive precautions during the trial and for 6 months
following the last dose of study drug.
[10] Females with child-bearing potential must have had a negative serum
pregnancy test = 7 days prior to the first dose of study drug.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
[14] Are currently enrolled in, or discontinued within the last 30 days from,
a clinical trial involving an off-label use of an investigational drug or
device (other than the study drug used in this study), or concurrently
enrolled in any other type of medical research judged not to be
scientifically or medically compatible with this study.
[15] Have received = 2 previous chemotherapy-containing systemic
treatment regimens for metastatic melanoma. An immunotherapy or
antibody-based regimen [including biologic agents and vaccinationbased
treatments], or treatment with a targeted agent (e.g BRAF or c-
Kit inhibitor, is not counted as a prior treatment regimen for
determining study eligibility, unless either was combined with a
cytotoxic drug).
[16] Any previous treatment with paclitaxel or a paclitaxel-containing
regimen for metastatic melanoma.
[17] Have active central nervous system (CNS) or leptomeningeal
metastasis (brain metastasis) at the time of study entry. Patients with
signs or symptoms of neurological compromise should have
appropriate radiographic imaging performed before study entry to rule
out occult brain metastasis. Patients with a history of a solitary CNS
metastasis previously treated with curative intent (e.g., stereotactic
radiation or surgery) and not requiring steroids are eligible.
[18] Have serious concomitant disorders, including active bacterial, fungal,
or viral infection, incompatible with the study (at the discretion of the
investigator).
[19] Have a second primary malignancy that could affect compliance with
the protocol or interpretation of the results. NOTE: Patients with
adequately treated carcinoma of the skin (non-melanoma) and patients
with a prior history of malignancy who have been disease-free for
more than 2 years are eligible.
[20] Have serious preexisting medical conditions (at the investigator’s
discretion).
[21] Are receiving warfarin.
[22] Have previously completed or withdrawn from this study or any other
study investigating tasisulam.
[23] Have a known hypersensitivity to paclitaxel or Cremophor® EL
(polyoxyethylated castor oil).
[24] Are pregnant or lactating.
[25] Have primary ocular or mucosal melanoma.
[26] Have received a recent (within 30 days before enrollment) or are
receiving concurrent yellow fever vaccination.
[27] Have known positive test results in human immunodeficiency virus
(HIV), hepatitis B surface antigen (HBSAg), or hepatitis C antibodies
(HCAb).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Second line metastatic melanoma
MedDRA version: 12.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma

Intervention(s)

Product Name: Tasisulam Sodium
Product Code: LY573636
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: tasisulam sodium
CAS Number: 519055-63-1
Current Sponsor code: LY573636
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 250-1000

Trade Name: Paclitaxel
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: PACLITAXEL
CAS Number: 33069-62-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6-

Primary Outcome(s)

Primary end point(s): overall survival

Secondary Objective: The secondary objectives of the study are:
- to compare the following between treatment arms:
• time-to-event efficacy variables, including: PFS, duration of response (DoR), deterioration in the FACT-M TOI score
• objective tumor response rate
• therapeutic benefit rate
• measures of relative safety, including quantitative & qualitative laboratory &
non-laboratory toxicities
• health outcome measures
- Translational Research (TR):
• to evaluate the treatment-specific and treatment-independent effects of BRAF and
c-Kit mutational status on measures of clinical efficacy,
• to evaluate the treatment-specific effects of genetic markers, including on measures of clinical efficacy & toxicity.
• to assess other exploratory biomarkers relevant to tasisulam and paclitaxel
• to assess other exploratory biomarkers relevant to the disease state of melanoma
• to assess the association between other exploratory biomarkers & clinical
outcome.

Main Objective: The primary objective of this study is to compare the overall survival (OS) of patients
who have received one prior regimen of dacarbazine or temozolomide-based chemotherapy for metastatic malignant melanoma when treated with either tasisulam or paclitaxel.

Secondary ID(s)

2009-014591-21-DE

H8K-MC-JZAO