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MSB0010445 and Stereotactic Body Radiation Therapy in Advanced Melanoma

Primary Purpose

Melanoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
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)
Sponsored by
EMD Serono
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma focused on measuring Melanoma, MSB0010445, Dose limiting toxicity, Stereotactic body radiation therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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

Sites / Locations

  • Please Contact U.S. Medical Information

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

MSB0010445 Low Dose Cohort 0.3 mg/kg

MSB0010445 Intermediate Dose Cohort 1.0 mg/kg

MSB0010445 High Dose Cohort 1.8 mg/kg

MSB0010445 High Dose Cohort 2.4 mg/kg

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
October 25, 2013
Last Updated
September 14, 2016
Sponsor
EMD Serono
Collaborators
Merck KGaA, Darmstadt, Germany
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1. Study Identification

Unique Protocol Identification Number
NCT01973608
Brief Title
MSB0010445 and Stereotactic Body Radiation Therapy in Advanced Melanoma
Official Title
A Safety Study for MSB0010445 in Combination With Stereotactic Body Radiation in Advanced Melanoma Subjects Following Prior Treatment With Ipilimumab
Study Type
Interventional

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Terminated
Why Stopped
The study is terminated prematurely as the sponsor decided to discontinue program of NHS-IL2 [MSB0010445]
Study Start Date
January 2014 (undefined)
Primary Completion Date
April 2015 (Actual)
Study Completion Date
June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
EMD Serono
Collaborators
Merck KGaA, Darmstadt, Germany

4. Oversight

5. Study Description

Brief 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 radiation therapy (SBRT).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
Melanoma, MSB0010445, Dose limiting toxicity, Stereotactic body radiation therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
MSB0010445 Low Dose Cohort 0.3 mg/kg
Arm Type
Experimental
Arm Title
MSB0010445 Intermediate Dose Cohort 1.0 mg/kg
Arm Type
Experimental
Arm Title
MSB0010445 High Dose Cohort 1.8 mg/kg
Arm Type
Experimental
Arm Title
MSB0010445 High Dose Cohort 2.4 mg/kg
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
MSB0010445 (0.3 milligram per kilogram [mg/kg])
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
MSB0010445 (1.0 mg/kg)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
MSB0010445 (1.8 mg/kg)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
MSB0010445 (2.4 mg/kg)
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
Stereotactic Body Radiation Therapy (SBRT)
Intervention Description
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).
Primary Outcome Measure Information:
Title
Number of Subjects With at Least 1 Dose Limiting Toxicity (DLT)
Description
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.
Time Frame
Baseline up to Day 21
Secondary Outcome Measure Information:
Title
Number of Subjects With Best Overall Response (BOR) According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1
Description
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.
Time Frame
Screening up to 28 days after last dose of drug; assessed up to maximum of 1.41 years
Title
Number of Subjects With Treatment-Emergent Adverse Events (AEs) or Serious AEs
Description
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.
Time Frame
Screening up to 28 days after last dose of drug; assessed up to maximum of 1.41 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
EMD Serono, Inc., Rockland MA, a subsidiary of Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
Please Contact U.S. Medical Information
City
Rockland
State/Province
Massachusetts
Country
United States

12. IPD Sharing Statement

Learn more about this trial

MSB0010445 and Stereotactic Body Radiation Therapy in Advanced Melanoma

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