MSB0010445 and Stereotactic Body Radiation Therapy in Advanced Melanoma

NCT ID: NCT01973608

Last Updated: 2016-10-31

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2015-06-30

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).

Conditions

Melanoma

Keywords

Melanoma; MSB0010445; Dose limiting toxicity; Stereotactic body radiation therapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MSB0010445 Low Dose Cohort 0.3 mg/kg

Group Type: EXPERIMENTAL

MSB0010445 (0.3 milligram per kilogram [mg/kg])

Intervention Type: 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.

Stereotactic Body Radiation Therapy (SBRT)

Intervention Type: 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).

MSB0010445 Intermediate Dose Cohort 1.0 mg/kg

Group Type: EXPERIMENTAL

MSB0010445 (1.0 mg/kg)

Intervention Type: 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.

Stereotactic Body Radiation Therapy (SBRT)

Intervention Type: 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).

MSB0010445 High Dose Cohort 1.8 mg/kg

Group Type: EXPERIMENTAL

MSB0010445 (1.8 mg/kg)

Intervention Type: 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.

Stereotactic Body Radiation Therapy (SBRT)

Intervention Type: 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).

MSB0010445 High Dose Cohort 2.4 mg/kg

Group Type: EXPERIMENTAL

MSB0010445 (2.4 mg/kg)

Intervention Type: 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)

Intervention Type: 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).

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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).

Intervention Type: RADIATION

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: collaborator

EMD Serono

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

EMD Serono, Inc., Rockland MA, a subsidiary of Merck KGaA, Darmstadt, Germany

Locations

Please Contact U.S. Medical Information

Rockland, Massachusetts, United States

Countries

United States

Other Identifiers

EMR 062235-005

Identifier Type: -

Identifier Source: org_study_id