Study of Taxoprexin Injection vs. Dacarbazine in Patients With Metastatic Malignant Melanoma

Phase III Study of Taxoprexin Injection vs. Dacarbazine in Patients With Metastatic Malignant Melanoma

The primary objective of this trial is to compare the survival of patients with metastatic malignant melanoma treated with Taxoprexin Injection to those treated with Dacarbazine. In addition, the response rate to each drug, response duration, time to progression and time to treatment failure will be measured. Toxicity will be evaluated and compared between the two groups.

Study Overview

• Status: Terminated
• Conditions: Malignant Melanoma
• Intervention / Treatment: Drug: Taxoprexin; Drug: Dacarbazine

Detailed Description

This was a randomized, multi-center, open-label Phase III study in patients with histologically confirmed metastatic malignant melanoma. Patients received either Taxoprexin® at a starting dose of 900 mg/m2 intravenously by 2-hour infusion on Day 1 every 3 weeks or dacarbazine at a starting dose of 1000 mg/m2 intravenously over at least 30 minutes once every 3 weeks. Treatment continued until progression of disease, intolerable toxicity, refusal of continued treatment by the patient, or, in the investigator's opinion, treatment discontinued. Disease status was assessed every 6 to 8 weeks using standard imaging techniques. All images were forwarded to the sponsor and archived. Following the end of protocol treatment, further treatment was at the investigator's discretion but no cross-over was planned. All patients were followed until death

• Study Type: Interventional
• Enrollment (Actual): 393
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Norristown, Pennsylvania, United States, 19403
      • Luitpold Pharmaceuticals, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have malignant melanoma, and documented metastatic disease.
• Patients must have at least one unidimensionally measurable lesion.
• Patients must not have received prior systemic chemotherapy for metastatic disease. Prior treatment with immunotherapy or vaccine therapy is allowed provided there is documentation of disease progression.
• At least 6 weeks (42 days) since any prior immunotherapy, cytokine, biologic, vaccine or other therapy unless patients have progressed during immunotherapy.
• At least 4 weeks (28 days) since any prior radiotherapy.
• Lesions being used to assess disease status may not have been radiated.
• Patients must have Eastern Cooperative Oncology Group performance status of 0 - 2.
• Patients must be >= 18 years of age.
• Patients must have adequate renal and liver function
• Patients must have adequate bone marrow function.
• Life expectancy of at least 3 months.
• Patients must sign an informed consent form indicating that they are aware of the investigational nature of this study and in keeping with the policies of the institution.

Exclusion Criteria:

• Patients who have received prior therapy with any taxane or dacarbazine.
• Patients whose primary site is the eye.
• Patients who have a past or current history of neoplasm other than the entry diagnosis, except for curatively treated non-melanoma skin cancer or carcinoma in situ of the cervix or other cancers cured by surgery alone with a disease-free survival longer than 5 years.
• Patients with uncontrolled brain metastasis.
• Patients who are pregnant or nursing and patients who are not practicing an acceptable method of birth control. Patients may not breastfeed while on this study.
• Patients with current active infections requiring anti-infectious treatment (e.g., antibiotics, antivirals, or antifungals).
• Patients with current peripheral neuropathy of any etiology that is greater than grade 1.
• Patients with unstable or serious concurrent medical conditions are excluded.
• Patients with a known hypersensitivity to Cremophor.
• Patients must not have had recent major surgery within the past 14 days or large field radiation therapy, chemotherapy, endocrine therapy in the last 28 days, or biologic therapy in the last 42 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Taxoprexin; Taxoprexin® 900 mg/m² intravenously every 3 weeks	Drug: Taxoprexin; Administered by intravenous infusion over 2 hour infusion on Day 1 followed by a 20-day observation period for a total of 21 days (three weeks) per course; Other Names: Docosahexaenoic acid (DHA)-paclitaxel
Active Comparator: Dacarbazine; Dacarbazine 1000 mg/m² intravenously every 3 weeks.	Drug: Dacarbazine; Administered by intravenous infusion over 30 minutes on Day 1 followed by a 20-day observation period for a total of 21 days (three weeks) per course; Other Names: Imidazole carboxamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Participant Survival	Overall survival was defined as the time from the day of randomization to participant death or the termination of the study, whichever occurs first. Participants were contacted monthly for survival information.	Up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved an Objective Complete Response or Partial Response	Antitumor response was defined as the percentage of participants who achieved an objective response (Confirmed Response [CR] or Partial Response [PR]), confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. Response was based on the blinded radiological review using Response Evaluation Criteria in Solid Tumors (RECIST) response guidelines, Version 1.0. A complete response was defined as a disappearance of all target lesions determined by 2 consecutive observations not less than 4 weeks apart. Partial response was defined as a 30% decrease in the sum of the longest diameters (LD) of target lesions, taking as reference the baseline sum of LD determined by 2 consecutive observations not less than 4 weeks apart.	Assessed every 6 weeks, up to 38 months
Duration of Response	Duration of overall response was a measurement from the time measure criteria was met for confirmed complete response or partial response (whichever was first recorded) until the first date that recurrent of progressive disease was objectively documented (taking as reference for progressive disease the smallest measurement recorded since treatment started).	Assessed every 6 weeks, up to 36 months
Time to Progression (TPP)	Progression free survival time was defined as the time from the day of randomization to the start of documented progression, based on the blinded radiological review response assessment. Progressive disease was defined as a ≥ 20% increase in the sum of longest diameter (SLD) of target lesions, taking as reference the smallest SLD recorded since the treatment started or the appearance of one or more new lesions	Assessed every 6 weeks until progression or death, up to 36 months
Time to Failure (TTF)	Time to Failure (TTF) was defined as the time from the day of randomization to the discontinuation of protocol treatment for any reason.	Baseline to stopping treatment, up to 36 months

Collaborators and Investigators

• Sponsor: American Regent, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2002
• Primary Completion (Actual): October 27, 2007
• Study Completion (Actual): October 27, 2007

Study Registration Dates

• First Submitted: July 13, 2004
• First Submitted That Met QC Criteria: July 15, 2004
• First Posted (Estimated): July 16, 2004

Study Record Updates

• Last Update Posted (Actual): July 23, 2025
• Last Update Submitted That Met QC Criteria: July 21, 2025
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Dacarbazine; Paclitaxel; Imidazole
• Other Study ID Numbers: P01-02-17

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No