MSB0010445 and Stereotactic Body Radiation Therapy in Advanced Melanoma
14 september 2016 uppdaterad av: EMD Serono
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).
Studieöversikt
Status
Avslutad
Betingelser
Studietyp
Interventionell
Inskrivning (Faktisk)
12
Fas
- Fas 2
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
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Massachusetts
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Rockland, Massachusetts, Förenta staterna
- Please Contact U.S. Medical Information
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Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år och äldre (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
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
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
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Experimentell: MSB0010445 Low Dose Cohort 0.3 mg/kg
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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.
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).
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Experimentell: MSB0010445 Intermediate Dose Cohort 1.0 mg/kg
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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 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.
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Experimentell: MSB0010445 High Dose Cohort 1.8 mg/kg
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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 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.
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Experimentell: MSB0010445 High Dose Cohort 2.4 mg/kg
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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 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.
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
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Number of Subjects With at Least 1 Dose Limiting Toxicity (DLT)
Tidsram: Baseline up to Day 21
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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.
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Baseline up to Day 21
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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
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Number of Subjects With Best Overall Response (BOR) According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1
Tidsram: Screening up to 28 days after last dose of drug; assessed up to maximum of 1.41 years
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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.
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Screening up to 28 days after last dose of drug; assessed up to maximum of 1.41 years
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Number of Subjects With Treatment-Emergent Adverse Events (AEs) or Serious AEs
Tidsram: Screening up to 28 days after last dose of drug; assessed up to maximum of 1.41 years
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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.
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Screening up to 28 days after last dose of drug; assessed up to maximum of 1.41 years
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Samarbetspartners och utredare
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Sponsor
Samarbetspartners
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart
1 januari 2014
Primärt slutförande (Faktisk)
1 april 2015
Avslutad studie (Faktisk)
1 juni 2015
Studieregistreringsdatum
Först inskickad
25 oktober 2013
Först inskickad som uppfyllde QC-kriterierna
25 oktober 2013
Första postat (Uppskatta)
31 oktober 2013
Uppdateringar av studier
Senaste uppdatering publicerad (Uppskatta)
31 oktober 2016
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
14 september 2016
Senast verifierad
1 september 2016
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- EMR 062235-005
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