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NCT Number: NCT01335009

Efficacy Study of Pharmacokinetic(PK)/Pharmacodynamic(PD) Relationship of Monotherapy MORAb-004 in Metastatic Melanoma

This is a global, Phase 2, open label, dose selection, proof-of-concept study to assess progression free survival in subjects with metastatic melanoma.

Approximately 80 subjects at 29 sites in the U.S., U.K., Germany and Australia will be randomized into one of two dose groups: 2 mg/kg, 4 mg/kg. Weekly treatment will continue until disease progression.

Subjects must have measurable disease by CT Scan or MRI and must have completed at least one prior round of chemotherapy.

Subjects will be assessed for Efficacy, PK/PD, Overall survival, and Safety (Adverse Events/Adverse Events of Interest, Electrocardiograms (ECG's), clinical labs, physical exams/vital signs, tolerability).

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Key information

Conditions

Metastatic Melanoma Melanoma Neoplasm Metastasis Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Neoplastic Processes Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Pathologic Processes Pathological Conditions, Signs and Symptoms Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Sydney Cancer Center - Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia

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About this study

MORAb-004 is a monoclonal antibody directed against endosialin, a cell surface glycoprotein, which is expressed on cells involved in tumor vasculature. Studies have found endosialin to play a key role in tumor growth and neovessel formation in numerous cancer types including melanoma. Preclinical pharmacological studies have shown that MORAb-004 is a potentially useful anti-cancer agent. This clinical trial is being performed to determine the efficacy of MORAb-004 at two dose levels in subjects with metastatic melanoma, as well as to establish serum pharmacokinetics and pharmacodynamics of the antibody.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Be surgically sterile or consent to use a medically acceptable method of contraception throughout the study period.
  • Histologically confirmed diagnosis of metastatic melanoma
  • At least 1 prior systemic treatment for metastatic melanoma with disease progression following treatment
  • Measurable disease, as defined by RECIST v1.1, assessed within 4 weeks prior to study entry
  • At least 3 week interval between first infusion of test article and most recent prior systemic anticancer therapy. All treatment-associated toxicity must be resolved to less than or equal to Grade 1 before the administration of MORAb-004
  • Have a life expectancy of at least 3 months as estimated by the investigator
  • Have other significant medical conditions well-controlled and stable, in the opinion of the investigator, for at least 30 days prior to Study Day 1
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Have sites of disease amenable to the protocol-specified biopsy (Note: All participants will have protocol-specified biopsy at Screening. The second, on-treatment biopsy will be mandatory in the first 30 randomized participants only. For all other participants, the second biopsy is optional.
  • Laboratory tests results prior to Study Day 1 within limits as outlined in protocol

Exclusion criteria

  • Have received no prior systemic treatment for metastatic melanoma
  • Evidence of other active malignancy requiring treatment within the last 5 years (other than basal cell or squamous cell carcinoma of the skin), or active brain metastasis
  • Clinically significant heart disease (Congestive heart failure of New York Heart Association [NYHA] Class 3 or 4, angina not well controlled by medication, or myocardial infarction within 6 mos.), or ECGs demonstrating clinically significant arrhythmias
  • Have any other serious systemic disease, including active bacterial or fungal infection, or any medical condition requiring cytotoxic therapy or chronic (at least 4 consecutive weeks) systemic corticosteroid use
  • Have active viral hepatitis or symptomatic Human immunodeficiency virus (HIV) infection
  • Be breast-feeding, pregnant, or likely to become pregnant during the study
  • Known allergic reaction to a prior monoclonal antibody therapy
  • Previous treatment with MORAb-004
  • Brain metastasis

Treatment and study plan

MORAb-004 (monoclonal antibody)

Biological

Subjects will receive one cycle of treatment with MORAb-004, administered intravenously, on Days 1, 8, 15, and 22 (4 administrations per cycle). Additional cycles will continue without interruption until disease progression occurs or clinical or symptomatic progression as suggested by an investigator.

Primary outcomes

  1. Percentage of Participants With Progression-free Survival (PFS) at Week 24

    Time frame: Week 24

    PFS was defined as the time (in weeks) from the date of randomization to the date of the first sign of disease progression (PD) based on Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, or date of death, regardless of cause. PD greater than or equal to (>=) 20 percent (%) increase in the nadir of total tumor burden (TTB) (minimum 5 millimeter [mm]). Participants who were alive with no disease progression had their PFS time censored at the date of their last tumor assessment. Participants who received a new anti-cancer therapy before disease progression had their PFS time censored at the date of their last tumor assessment before the new anti-cancer therapy was started. PFS was analyzed using Kaplan Meier method.

Secondary outcomes

  1. Percentage of Participants With PFS at Weeks 16 and 52

    Time frame: Week 16 and Week 52

    PFS was defined as the time (in weeks) from the date of randomization to the date of the first observation of PD (RECIST version 1.1) or date of death, regardless of the cause. PD >=20% increase in the nadir of TTB (minimum 5 mm). Participants who were alive with no disease progression had their PFS time censored at the date of their last tumor assessment. Participants who received new anti-cancer therapy before disease progression had their PFS time censored at the date of their last tumor assessment before the new anti-cancer therapy was initiated. PFS was based on the Kaplan-Meier method.

  2. Overall Survival (OS)

    Time frame: Date of first study treatment (Day 1) to date of death or up to approximately 2 years 7 months

    OS was defined as the time (in weeks) from the date of randomization to the date of death, regardless of cause. In the absence of death confirmation, or for participants alive at the time of analysis, the survival time was censored at the date of the last study follow-up. OS was calculated using the Kaplan-Meier method. As per planned analysis, efficacy outcomes was planned to be analyzed until cut-off date (02 December 2013).

  3. Percentage of Participants With Overall Response

    Time frame: Date of first study treatment (Day 1) to complete response or partial response, assessed up to approximately 2 years 7 months

    ORR was defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) that occurred (defined by RECIST version 1.1) using CT/MRI. Per RECIST 1.1, CR= disappearance of all lesions; PR greater than or equal to (>=) 30percent (%) decrease from baseline in TTB. As per planned analysis, efficacy outcomes was planned to be analyzed until cut-off date (02 December 2013).

  4. Optimal Biologic Dosing (OBD) of Morab-004

    Time frame: Day 1 Cycle 1 (Cycle length = 28 days)

    OBD is defined as the dose level/exposure level at which three parameters are met: 1) adequate pharmacokinetic (PK) profile with a serum half-life (t1/2) of >=48 hours, 2) at least minimal demonstration of antitumor efficacy (50% or greater PFS rate at 16 weeks), and 3) change of 25% or greater from baseline value in any of the pharmacodynamic (PD) parameters assessed in the study in 30% of participants at that dose level.

Sponsors and collaborators

Lead sponsor

Eisai Inc.

Industry

Registry information

Official study title

A Study of the Efficacy and PK/PD Relationship of Monotherapy MORAb-004 in Subjects With Metastatic Melanoma

Important dates

Study start
2011
Primary completion
2013
Study completion
2020
First posted
Apr 13, 2011
Registry last updated
Sep 1, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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