MelanomaPhase 2NCT01973608
MSB0010445 and Stereotactic Body Radiation Therapy in Advanced Melanoma
A Phase 2 study testing MSB0010445 (0.3 milligram per kilogram [mg/kg]), MSB0010445 (1.0 mg/kg) and MSB0010445 (1.8 mg/kg) in people with Melanoma, run by EMD Serono at 1 site in United States.
Trial summary
This is a Phase 2a, open-label, parallel group, partly randomized dose escalation trial to assess the safety and efficacy of a low dose, an intermediate dose, and high dose MSB0010445 given by intravenous infusion to subjects with advanced (unresectable or metastatic) melanoma in combination with stereotactic body… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- MSB0010445 (0.3 milligram per kilogram [mg/kg]), MSB0010445 (1.0 mg/kg) and MSB0010445 (1.8 mg/kg)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2014to Jun 2015
- 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
- Advanced unresectable or metastatic melanoma, previously treated with ipilimumab; anti-melanoma treatments, including anti-PD/PD-L1 or any other immunotherapy, are allowed provided no treatment from last dose of that treatment to trial enrolment
- Subjects need to have
- one lesion that can be irradiated
- at least 1 measurable lesion outside the radiation field, different from the lesion that will be irradiated
- one lesion that can be biopsied before treatment with SBRT and MSB0010445
- one lesion outside the radiation field that can be biopsied while on treatment with MSB0010445
Show all 13Show fewer
- The lesion that is biopsied at Baseline can be the lesion that will be irradiated
- The lesion that will be biopsied while on treatment should not be a lesion that has been irradiated or biopsied at Baseline
- Signed written informed consent
- Male and female subjects at least 18 years of age
- Life expectancy greater than or equal to (>=) 4 months
- Eastern cooperative oncology group (ECOG) performance status of 0 or 1
- Other protocol defined inclusion criteria could apply
Who cannot join
- Active central nervous system metastasis
- Treatment with systemic anti-cancer therapy within the 30 days before the first dose of SBRT
- Pre-existing pericardial effusion or history of Grade >=2 pleural effusion or ascites within 3 months before first dose of SBRT
- Concurrent systemic therapy with steroids or other immunosuppressive agents except short-term systemic steroids for allergic reactions
- Other protocol defined exclusion criteria could apply
Trial locations and contacts
1 site in 1 country.
United States1 site
Please Contact U.S. Medical Information
Rockland, Massachusetts
About this study
Official title: A Safety Study for MSB0010445 in Combination With Stereotactic Body Radiation in Advanced Melanoma Subjects Following Prior Treatment With Ipilimumab
This is a Phase 2a, open-label, parallel group, partly randomized dose escalation trial to assess the safety and efficacy of a low dose, an intermediate dose, and high dose MSB0010445 given by intravenous infusion to subjects with advanced (unresectable or metastatic) melanoma in combination with stereotactic body radiation therapy (SBRT).
- Conditions
- Melanoma
- Being tested
- MSB0010445 (0.3 milligram per kilogram [mg/kg]), MSB0010445 (1.0 mg/kg), MSB0010445 (1.8 mg/kg), MSB0010445 (2.4 mg/kg), Stereotactic Body Radiation Therapy (SBRT)
- Keywords
- Melanoma, MSB0010445, Dose limiting toxicity, Stereotactic body radiation therapy
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MSB0010445 (0.3 milligram per kilogram [mg/kg])Drug
MSB0010445 will be administered at a single dose of 0.3 mg/kg as intravenous (IV) infusion over approximately 1 hour every 3 weeks (q3w) for the first 12 Weeks as a part of induction phase followed by maintenance dose of 0.3 mg/kg drug every three weeks until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 will be performed 3 days after the last dose of Stereotactic Body Radiation Therapy (SBRT) to the targeted reference lesion.
MSB0010445 (1.0 mg/kg)Drug
MSB0010445 will be administered at a single dose of 1.0 mg/kg as IV infusion over approximately 1 hour q3w for the first 12 Weeks as a part of induction phase followed by maintenance dose of 0.3 mg/kg drug every three weeks until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 will be performed 3 days after the last dose of SBRT to the targeted reference lesion.
MSB0010445 (1.8 mg/kg)Drug
MSB0010445 will be administered at a single dose of 1.8 mg/kg as IV infusion over approximately 1 hour q3w for the first 12 Weeks as a part of induction phase followed by maintenance dose of 0.3 mg/kg drug every three weeks until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 will be performed 3 days after the last dose of SBRT to the targeted reference lesion.
MSB0010445 (2.4 mg/kg)Drug
MSB0010445 will be administered at a single dose of 2.4 mg/kg as IV infusion over approximately 1 hour q3w for the first 12 Weeks as a part of induction phase followed by maintenance dose of 0.3 mg/kg drug every three weeks until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 will be performed 3 days after the last dose of SBRT to the targeted reference lesion.
Stereotactic Body Radiation Therapy (SBRT)Radiation
SBRT will be administered using a dose and schedule recommended based upon the data showing the best abscopal effect using multiple fractions if one site will be targeted subject received 3 fractions (1 per day) of 8 Gray (Gy) each (total: 24 Gy). If the target lesion will be located in the thorax, the maximum total dose administered will be 18 Gy (3 x 6 Gy).
| Study group | Role | What they receive |
|---|---|---|
| MSB0010445 Low Dose Cohort 0.3 mg/kg | Experimental | Not described Receives: Drug: MSB0010445 (0.3 milligram per kilogram [mg/kg]); Radiation: Stereotactic Body Radiation Therapy (SBRT) |
| MSB0010445 Intermediate Dose Cohort 1.0 mg/kg | Experimental | Not described Receives: Drug: MSB0010445 (1.0 mg/kg); Radiation: Stereotactic Body Radiation Therapy (SBRT) |
| MSB0010445 High Dose Cohort 1.8 mg/kg | Experimental | Not described Receives: Drug: MSB0010445 (1.8 mg/kg); Radiation: Stereotactic Body Radiation Therapy (SBRT) |
| MSB0010445 High Dose Cohort 2.4 mg/kg | Experimental | Not described Receives: Drug: MSB0010445 (2.4 mg/kg); Radiation: Stereotactic Body Radiation Therapy (SBRT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With at Least 1 Dose Limiting Toxicity (DLT)
DLT was defined as any Grade>= 3 toxicity related to drug, occurring during 21 days post first dose of drug except Grade 3 infusion-related adverse reaction resolving within 6 hours and Transient (<=6 hours) Grade 3 flu-like symptoms/fever controlled with medical management; Transient (<= 24 hours) Grade 3 fatigue, local reactions, headache, nausea, emesis that resolved to <= Grade 1; Grade 3 skin toxicity ,Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 8 x upper limit of normal (ULN)/total bilirubin < 5 x ULN resolving to <= Grade 1 in <7 days after medical management; Grade 3 diarrhea controlled with maximal medical management within 72 hours; Grade 4 lymphopenia that resolves to <= Grade 1 within 7 days \& with no clinical manifestations; Grade 3 lab abnormality with no clinical correlation and resolves to <= Grade 1 within 7 days with adequate medical management Tumor flare defined as local pain, irritation or rash localized at sites of known/suspected tumor.
Measured: Baseline up to Day 21
Secondary outcomes (2)
Number of Subjects With Best Overall Response (BOR) According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1
BOR was defined as a confirmed complete response (CR) or partial response (PR) during second-line treatment. For target lesions (TLs), CR was defined as the disappearance of all TLs, and PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the baseline SLD. For non-target lesions (NTLs), CR was defined as the disappearance of all NTLs and normalization of tumor marker levels.
Measured: Screening up to 28 days after last dose of drug; assessed up to maximum of 1.41 years
Number of Subjects With Treatment-Emergent Adverse Events (AEs) or Serious AEs
TEAE was defined as an AE that started on or after the first administration of SBRT. An SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/ significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Measured: Screening up to 28 days after last dose of drug; assessed up to maximum of 1.41 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2013 (estimated)
- Study startJan 2014
- Primary completionApr 2015
- Study completionJun 2015
Why it stopped: The study is terminated prematurely as the sponsor decided to discontinue program of NHS-IL2 \[MSB0010445\]
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 MelanomaStudies of the same condition, open and under way.
- 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
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- EMD Serono
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, EMD Serono, Inc., Rockland MA, a subsidiary of Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01973608
- Sponsor's protocol ID
- EMR 062235-005
- Status last verified
- Sep 2016
- First submitted
- 25 Oct 2013
- Last updated
- 31 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Safety Study for MSB0010445 in Combination With Stereotactic Body Radiation in Advanced Melanoma Subjects Following Prior Treatment With Ipilimumab
- ClinicalTrials.gov ID
- NCT01973608
- Acronym / sponsor ID
- EMR 062235-005
- Conditions
- Melanoma
- Keywords
- Melanoma, MSB0010445, Dose limiting toxicity, Stereotactic body radiation therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study is terminated prematurely as the sponsor decided to discontinue program of NHS-IL2 \[MSB0010445\]
- Enrolment
- 12 participants (actual)
- Lead sponsor
- EMD SeronoIndustry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Study start
- Jan 2014
- Primary completion
- Apr 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 31 Oct 2013 (estimated)
- Results
- Posted 31 Oct 2016
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 Phase 2a, open-label, parallel group, partly randomized dose escalation trial to assess the safety and efficacy of a low dose, an intermediate dose, and high dose MSB0010445 given by intravenous infusion to subjects with advanced (unresectable or metastatic) melanoma in combination with stereotactic body radiation therapy (SBRT).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| MSB0010445 Low Dose Cohort 0.3 mg/kg | Experimental | Drug: MSB0010445 (0.3 milligram per kilogram [mg/kg]), Radiation: Stereotactic Body Radiation Therapy (SBRT) |
| MSB0010445 Intermediate Dose Cohort 1.0 mg/kg | Experimental | Drug: MSB0010445 (1.0 mg/kg), Radiation: Stereotactic Body Radiation Therapy (SBRT) |
| MSB0010445 High Dose Cohort 1.8 mg/kg | Experimental | Drug: MSB0010445 (1.8 mg/kg), Radiation: Stereotactic Body Radiation Therapy (SBRT) |
| MSB0010445 High Dose Cohort 2.4 mg/kg | Experimental | Drug: MSB0010445 (2.4 mg/kg), Radiation: Stereotactic Body Radiation Therapy (SBRT) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Advanced unresectable or metastatic melanoma, previously treated with ipilimumab; anti-melanoma treatments, including anti-PD/PD-L1 or any other immunotherapy, are allowed provided no treatment from last dose of that treatment to trial enrolment
- Subjects need to have
- The lesion that is biopsied at Baseline can be the lesion that will be irradiated
- The lesion that will be biopsied while on treatment should not be a lesion that has been irradiated or biopsied at Baseline
- Signed written informed consent
Key exclusion criteria (5 listed)
- Active central nervous system metastasis
- Treatment with systemic anti-cancer therapy within the 30 days before the first dose of SBRT
- Pre-existing pericardial effusion or history of Grade >=2 pleural effusion or ascites within 3 months before first dose of SBRT
- Concurrent systemic therapy with steroids or other immunosuppressive agents except short-term systemic steroids for allergic reactions
- Other protocol defined exclusion criteria could apply
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 |
|---|---|---|
| MSB0010445 (0.3 milligram per kilogram [mg/kg])MSB0010445 will be administered at a single dose of 0.3 mg/kg as intravenous (IV) infusion over approximately 1 hour every 3 weeks (q3w) for the first 12 Weeks as a part of induction phase followed by maintenance dose of 0.3 mg/kg drug every three weeks until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 will be performed 3 days after the last dose of Stereotactic Body Radiation Therapy (SBRT) to the targeted reference lesion. | Drug | MSB0010445 Low Dose Cohort 0.3 mg/kg |
| MSB0010445 (1.0 mg/kg)MSB0010445 will be administered at a single dose of 1.0 mg/kg as IV infusion over approximately 1 hour q3w for the first 12 Weeks as a part of induction phase followed by maintenance dose of 0.3 mg/kg drug every three weeks until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 will be performed 3 days after the last dose of SBRT to the targeted reference lesion. | Drug | MSB0010445 Intermediate Dose Cohort 1.0 mg/kg |
| MSB0010445 (1.8 mg/kg)MSB0010445 will be administered at a single dose of 1.8 mg/kg as IV infusion over approximately 1 hour q3w for the first 12 Weeks as a part of induction phase followed by maintenance dose of 0.3 mg/kg drug every three weeks until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 will be performed 3 days after the last dose of SBRT to the targeted reference lesion. | Drug | MSB0010445 High Dose Cohort 1.8 mg/kg |
| MSB0010445 (2.4 mg/kg)MSB0010445 will be administered at a single dose of 2.4 mg/kg as IV infusion over approximately 1 hour q3w for the first 12 Weeks as a part of induction phase followed by maintenance dose of 0.3 mg/kg drug every three weeks until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 will be performed 3 days after the last dose of SBRT to the targeted reference lesion. | Drug | MSB0010445 High Dose Cohort 2.4 mg/kg |
| Stereotactic Body Radiation Therapy (SBRT)SBRT will be administered using a dose and schedule recommended based upon the data showing the best abscopal effect using multiple fractions if one site will be targeted subject received 3 fractions (1 per day) of 8 Gray (Gy) each (total: 24 Gy). If the target lesion will be located in the thorax, the maximum total dose administered will be 18 Gy (3 x 6 Gy). | Radiation | MSB0010445 High Dose Cohort 1.8 mg/kg, MSB0010445 High Dose Cohort 2.4 mg/kg, MSB0010445 Intermediate Dose Cohort 1.0 mg/kg, MSB0010445 Low Dose Cohort 0.3 mg/kg |
Primary outcome
Number of Subjects With at Least 1 Dose Limiting Toxicity (DLT)
Time frame: Baseline up to Day 21
DLT was defined as any Grade>= 3 toxicity related to drug, occurring during 21 days post first dose of drug except Grade 3 infusion-related adverse reaction resolving within 6 hours and Transient (<=6 hours) Grade 3 flu-like symptoms/fever controlled with medical management; Transient (<= 24 hours) Grade 3 fatigue, local reactions, headache, nausea, emesis that resolved to <= Grade 1; Grade 3 skin toxicity ,Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 8 x upper limit of normal (ULN)/total bilirubin < 5 x ULN resolving to <= Grade 1 in <7 days after medical management; Grade 3 diarrhea controlled with maximal medical management within 72 hours; Grade 4 lymphopenia that resolves to <= Grade 1 within 7 days \& with no clinical manifestations; Grade 3 lab abnormality with no clinical correlation and resolves to <= Grade 1 within 7 days with adequate medical management Tumor flare defined as local pain, irritation or rash localized at sites of known/suspected tumor.
2 secondary outcomes
Number of Subjects With Best Overall Response (BOR) According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1
Time frame: Screening up to 28 days after last dose of drug; assessed up to maximum of 1.41 years
Number of Subjects With Treatment-Emergent Adverse Events (AEs) or Serious AEs
Time frame: Screening up to 28 days after last dose of drug; assessed up to maximum of 1.41 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2016.
- 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.
Medical Responsible study director
EMD Serono, Inc., Rockland MA, a subsidiary of Merck KGaA, Darmstadt, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MSB0010445 (0.3 milligram per kilogram [mg/kg]), MSB0010445 (1.0 mg/kg) and MSB0010445 (1.8 mg/kg) in people with Melanoma, run by EMD Serono at 1 site in United States.
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 13 inclusion and 5 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: stopped early, as of the sponsor's last update on 31 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 31 Oct 2016). 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?
Number of Subjects With at Least 1 Dose Limiting Toxicity (DLT) (time frame: Baseline up to Day 21). 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 31 Oct 2016.