MSB0010445 and Stereotactic Body Radiation Therapy in Advanced Melanoma

NCT01973608 | Terminated Phase 2 Results

• 1 other identifier: EMR 062235-005
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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

  Screening up to 28 days after last dose of drug; assessed up to maximum of 1.41 years

Study Arms (4)

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)

Interventions

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 Low Dose Cohort 0.3 mg/kg

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 Intermediate Dose Cohort 1.0 mg/kg

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 High Dose Cohort 1.8 mg/kg

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.

MSB0010445 High Dose Cohort 2.4 mg/kg

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).

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• EMD Serono: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (1)

Please Contact U.S. Medical Information

Rockland, Massachusetts, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Limitations and Caveats

The study was terminated early due to sponsor's decision to discontinue the development of MSB0010445. The decision to discontinue development of MSB0010445 was not related to any safety or efficacy concerns.

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2013
• First Posted: October 31, 2013
• Study Start: January 1, 2014
• Primary Completion: April 1, 2015
• Study Completion: June 1, 2015
• Last Updated: October 31, 2016
• Results First Posted: October 31, 2016

Record last verified: 2016-09

Locations

US (1)