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A Study of Tasisulam in Treating Participants With Malignant Melanoma

Phase 2
Completed
Conditions
Metastatic Melanoma
Interventions
Registration Number
NCT00383292
Lead Sponsor
Eli Lilly and Company
Brief Summary

The primary purpose of this study is to determine the objective response rate (complete and partial response) for participants who receive tasisulam after one prior systemic treatment for unresectable or metastatic melanoma.

Detailed Description

Participants will receive a 2-hour intravenous infusion of study drug (tasisulam) once every 28 days. Radiological imaging scans will be performed before the first dose of study drug and then after every other treatment. Participants will be assessed for clinical progression at every visit and for response approximately every 56 days (every other cycle).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
130
Inclusion Criteria
  • Diagnosis of malignant melanoma that is unresectable or metastatic (Stage III or IV)
  • Have received 1 previous systemic treatment regimen for unresectable or metastatic melanoma. An immunotherapy or antibody-based regimen (including vaccination-based treatments) is not counted as a prior treatment regimen for determining study eligibility, unless it was combined with a chemotherapeutic or targeted anti-cancer drug.
  • Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, immunotherapy, or other investigational therapy for at least 30 days
Exclusion Criteria
  • Serious pre-existing medical conditions
  • Have received two or more previous treatment regimens for unresectable or metastatic melanoma
  • Have a second primary cancer (unless disease-free to more than 2 years)
  • Active treatment with Warfarin (Coumadin)
  • Primary ocular or mucosal melanoma

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Tasisulamtasisulam-
Primary Outcome Measures
NameTimeMethod
Percentage of Participants Achieving Objective Response Rate (ORR) (Complete Response + Partial Response)Baseline to Measured Progressive Disease (up to 60 Months)

Participants achieved an objective response if they had a best overall response of complete response (CR) or partial response (PR). According to Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1), CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to \<10 mm, the disappearance of all non-target lesions, and the normalization of tumor marker levels (if tumor markers were initially above the upper limit of normal); PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter. For each participant who is not known to have died or to have had objective progression of disease as of the data-inclusion cut-off date for a particular analysis, duration of tumor response was to be censored at the date of the participant's last objective tumor assessment prior to that cut-off date.

Secondary Outcome Measures
NameTimeMethod
Overall Survival (OS) TimeBaseline to Death from Any Cause (up to 42 Months)

OS was defined as time from baseline to the date of death from any cause. Participants who were alive at the end of the follow-up period (or lost to follow-up) were censored on the last date the participant was known to be alive.

Health-Related Quality of Life: Functional Assessment of Cancer Therapy-General (FACT-G) ScoreBaseline to Study Completion (up to 60 Months)

FACT-G is a 27-item compilation of general questions divided into 4 primary health-related quality of life (HRQL) domains: Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, and Functional Well-Being. Total scores ranged from 0 to 172; higher scores = better HRQL.

Percentage of Participants Achieving Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (Clinical Response Rate)Baseline to Progressive Disease or Death Due to Any Cause (up to 60 Months)

Participants achieved disease control if they had a best overall response of PR, CR or SD. According to RECIST v1.1, CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to \<10 mm, the disappearance of all non-target lesions, and the normalization of tumor marker levels (if tumor markers were initially above the upper limit of normal \[ULN\]); PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter. SD was neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started. Clinical Response Rate was calculated as the number of participants who were free from progression (CR+PR+SD) for ≥2 cycles/number of participants who received at least 1 dose of tasisulam.

Duration of Overall Objective ResponseDate of Response to Date of Measured PD (up to 1 Year)

The duration of response was measured from the date of CR or PR to first date of documented PD or death and was censored at the date of the last assessment for responders who remained alive and did not have documented PD.

Duration of Stable Disease (SD)Baseline to Progressive Disease or Death Due to Any Cause (up to 1 Year)

Duration of SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study. SD is measured at the start of the study drug until progressive disease or death due to any cause, whichever is first. Censoring occurred if a participant did not have a complete baseline disease assessment, initiated on another anti-cancer therapy (censored at the date of the last complete objective progression-free disease assessment before initiation of the new therapy), was not known to have died or had objective progression as of the data inclusion cutoff date for analysis.

Progression-Free Survival (PFS)Baseline to Measured Progressive Disease or Death from Any Cause (up to 42 Months)

PFS was defined as the time from baseline until measured PD or death from any cause, whichever is first. According to Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1), PD was at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the 20% relative increase, the sum must have also demonstrated an absolute increase of at least 5 millimeters (mm). The appearance of 1 or more new lesions and/or unequivocal progression of existing nontarget lesions was also considered progression. Participants without objectively determined PD, who were alive at the end of the follow-up period (or lost to follow-up), were censored on the date of the participant's last complete radiographic tumor assessment; if no baseline or post-baseline radiologic assessment was available, the participant was censored at the date of randomization.

Pharmacokinetics: Plasma Clearance Rate of TasisulamCycle 1-3, Day 1, 8 and 15: Predose, End of Infusion, and Postinfusion
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration (Safety: Adverse Events)Baseline to Study Completion (up to 60 Months)

Data presented are the number of participants who experienced SAEs considered by the investigator to be related to study drug administration. A summary of SAEs and all other non-serious Adverse Event(s) (AEs), regardless of causality, is located in the Reported Adverse Event module.

Trial Locations

Locations (1)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

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Nedlands, Western Australia, Australia

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