Metastatic MelanomaPhase 2NCT01335009
Efficacy Study of Pharmacokinetic(PK)/Pharmacodynamic(PD) Relationship of Monotherapy MORAb-004 in Metastatic Melanoma
A Phase 2 study testing MORAb-004 (monoclonal antibody) in people with Metastatic Melanoma, run by Eisai Inc. at 29 sites in 4 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma
- What is being tested?
- MORAb-004 (monoclonal antibody)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 29 sitesin 4 countries
- Study dates
- 16 May 2011to 10 Apr 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- Known allergic reaction to a prior monoclonal antibody therapy
- Previous treatment with MORAb-004
- Brain metastasis
Trial locations and contacts
29 sites in 4 countries.
29 sites in 4 countries
United States20 sites
University of Colorado Cancer Center, Anschutz Cancer Pavilion
Aurora, Colorado, 80045
St. Luke's Hospital & Health Network
Bethlehem, Pennsylvania, 18051
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 19454
The University Of Chicago
Chicago, Illinois, 60637
Duke University Medical Center
Durham, North Carolina, 27710
University of Iowa Hospital
Iowa City, Iowa, 52242
The Angeles Clinic and Research Institute
Los Angeles, California, 90025
University of California Los Angeles
Los Angeles, California, 90095
University of Minnesota
Minneapolis, Minnesota, 19454
Atlantic Health
Morristown, New Jersey, 07962
Yale University
New Haven, Connecticut, 06520
New York University Cancer Institute
New York, New York, 10016
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Oncology Specialists, SC
Park Ridge, Illinois, 60068
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, 15232
University of Utah Huntsman Cancer Institute
Salt Lake City, Utah, 84112
Pinnacle Oncology
Scottsdale, Arizona, 19454
Washington University School of Medicine
St Louis, Missouri, 63110
Australia4 sites
Sydney Cancer Center - Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050
Newcastle Melanoma Unit, Calvery Mater Newcastle
Waratah, New South Wales, 2298
The Crown Princess Mary Cancer Centre, Westmead Hospital
Westmead, New South Wales, 2145
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
Germany3 sites
Universitatsklinikum Essen, Klinik fur Dermatologie
Essen, 45147
Universitats-Hautklinik
Mainz, 55131
Eberhard Karls University Tuebingen
Tübingen, 72076
United Kingdom2 sites
The Royal Marsden Hospital
London, SW3 6JJ
Weston Park Hospital
Sheffield, S10 2SJ
About this study
Official title: A Study of the Efficacy and PK/PD Relationship of Monotherapy MORAb-004 in Subjects With 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).
Read the detailed description
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.
- Conditions
- Metastatic Melanoma
- Being tested
- MORAb-004 (monoclonal antibody)
- Keywords
- melanoma, malignant, metastatic
- Medical subject headings
- Melanoma, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| MORAb-004, 2 mg/kg | Experimental | Biologic (monoclonal antibody) Receives: Biological: MORAb-004 (monoclonal antibody) |
| MORAb-004, 4 mg/kg | Experimental | Biologic (monoclonal antibody) Receives: Biological: MORAb-004 (monoclonal antibody) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Progression-free Survival (PFS) at 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.
Measured: Week 24
Secondary outcomes (4)
Percentage of Participants With PFS at Weeks 16 and 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.
Measured: Week 16 and Week 52
Overall Survival (OS)
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).
Measured: Date of first study treatment (Day 1) to date of death or up to approximately 2 years 7 months
Percentage of Participants With Overall Response
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).
Measured: Date of first study treatment (Day 1) to complete response or partial response, assessed up to approximately 2 years 7 months
Optimal Biologic Dosing (OBD) of Morab-004
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.
Measured: Day 1 Cycle 1 (Cycle length = 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2011 (estimated)
- Study start16 May 2011
- Primary completion2 Dec 2013
- Study completion10 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- More trials run by Eisai Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01335009
- Sponsor's protocol ID
- MORAb-004-201MEL
- Other IDs
- 2011-001282-40
- Status last verified
- Apr 2021
- First submitted
- 14 Mar 2011
- Last updated
- 1 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of the Efficacy and PK/PD Relationship of Monotherapy MORAb-004 in Subjects With Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT01335009
- Acronym / sponsor ID
- MORAb-004-201MEL
- Conditions
- Metastatic Melanoma
- Keywords
- melanoma, malignant, metastatic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Study start
- 16 May 2011 (actual)
- Primary completion
- 2 Dec 2013 (actual)
- Study completion
- 10 Apr 2020 (actual)
- First posted
- 13 Apr 2011 (estimated)
- Results
- Posted 1 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MORAb-004, 2 mg/kg | Experimental | Biological: MORAb-004 (monoclonal antibody)Biologic (monoclonal antibody) |
| MORAb-004, 4 mg/kg | Experimental | Biological: MORAb-004 (monoclonal antibody)Biologic (monoclonal antibody) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MORAb-004 (monoclonal antibody)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. | Biological | MORAb-004, 2 mg/kg, MORAb-004, 4 mg/kg |
Primary outcome
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.
4 secondary outcomes
Percentage of Participants With PFS at Weeks 16 and 52
Time frame: Week 16 and Week 52
Overall Survival (OS)
Time frame: Date of first study treatment (Day 1) to date of death or up to approximately 2 years 7 months
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
Optimal Biologic Dosing (OBD) of Morab-004
Time frame: Day 1 Cycle 1 (Cycle length = 28 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
29 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MORAb-004 (monoclonal antibody) in people with Metastatic Melanoma, run by Eisai Inc. at 29 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, Australia, Germany, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Progression-free Survival (PFS) at Week 24 (time frame: Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2021.