A Phase 1 Study of Nivolumab (BMS-936558) in Subjects With Advanced or Recurrent Malignancies (MDX1106-03)
keskiviikko 1. joulukuuta 2021 päivittänyt: Bristol-Myers Squibb
A Phase 1, Open-Label, Multicenter, Multidose, Dose Escalation Study of BMS-936558 (Nivolumab) in Subjects With Selected Advanced or Recurrent Malignancies
The purpose of this study is to determine the safety and effectiveness of MDX-1106 in patients with certain types of cancer.
Another purpose is to determine how MDX-1106 is absorbed and distributed within the body, and how it's eventually eliminated.
Tutkimuksen yleiskatsaus
Tila
Valmis
Ehdot
Opintotyyppi
Interventio
Ilmoittautuminen (Todellinen)
395
Vaihe
- Vaihe 1
Yhteystiedot ja paikat
Tässä osiossa on tutkimuksen suorittajien yhteystiedot ja tiedot siitä, missä tämä tutkimus suoritetaan.
Opiskelupaikat
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Arizona
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Scottsdale, Arizona, Yhdysvallat, 85258
- Pinnacle Oncology Hematology
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Connecticut
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New Haven, Connecticut, Yhdysvallat, 06520
- Yale University School Of Medicine
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Florida
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Tampa, Florida, Yhdysvallat, 33612-9497
- H. Lee Moffitt Cancer Center & Research Institute
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Maryland
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Baltimore, Maryland, Yhdysvallat, 21231
- Johns Hopkins University
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Massachusetts
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Boston, Massachusetts, Yhdysvallat, 02215
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, Yhdysvallat, 02215
- Dana Farber Cancer Institute
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Boston, Massachusetts, Yhdysvallat, 02215
- Massachusetts General Hospital
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Michigan
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Ann Arbor, Michigan, Yhdysvallat, 48109
- University of Michigan Cancer Center
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New York
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New York, New York, Yhdysvallat, 10065
- Memorial Sloan Kettering Nassau
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North Carolina
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Huntersville, North Carolina, Yhdysvallat, 28078
- Carolina Biooncology Institute
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Ohio
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Cincinnati, Ohio, Yhdysvallat, 45219
- Christ Hospital
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Tennessee
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Nashville, Tennessee, Yhdysvallat, 37203
- Sarah Cannon Research Institute
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Nashville, Tennessee, Yhdysvallat, 37232
- Vanderbilt-Ingram Cancer Ctr
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Osallistumiskriteerit
Tutkijat etsivät ihmisiä, jotka sopivat tiettyyn kuvaukseen, jota kutsutaan kelpoisuuskriteereiksi. Joitakin esimerkkejä näistä kriteereistä ovat henkilön yleinen terveydentila tai aiemmat hoidot.
Kelpoisuusvaatimukset
Opintokelpoiset iät
18 vuotta ja vanhemmat (Aikuinen, Vanhempi Aikuinen)
Hyväksyy terveitä vapaaehtoisia
Ei
Sukupuolet, jotka voivat opiskella
Kaikki
Kuvaus
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com
Inclusion Criteria:
- Subjects must have mCRPC,RCC, MEL, Non-small-cell lung cancer (NSCLC), or Colorectal Cancer (CRC), that is advanced (non-resectable), or recurrent and for which no alternative, curative standard exists
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
- Must have at least 1 measurable lesion
- Subjects with mCRPC and with only non-measurable bone lesions must have either progression new lesions or have Prostate-specific antigen (PSA) progression within the 6-week period before study administration
- At least 1 and up to 5 prior systemic therapies for advanced/recurrent disease
- Prior treated brain or meningeal metastases must be without Magnetic resonance imaging (MRI) evidence of progression for at least 8 weeks and off immunosuppressive doses of systemic steroids for at least 2 weeks before study drug administration
- Prior systemic radiation therapy must have been completed at least 4 weeks before study drug administration. Prior focal radiotherapy completed at least 2 weeks prior to study drug administration
- Immunosuppressive doses of systemic medications, such as steroids or absorbed topical steroids must be discontinued at least 2 weeks before study drug administration
- Prior surgery that required general anesthesia must be completed at least 2 weeks before study drug administration. Surgery requiring local/epidural anesthesia must be completed at least 72 hours before study drug administration
Exclusion Criteria:
- History of severe hypersensitivity reactions to other Monoclonal antibody (mAb)s
- Subjects with any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo or resolved childhood asthma/atopy
- Prior therapy with an anti-Programmed death-1 (PD-1), anti-PD-L1, anti-PD-L2, or anti- Cytotoxic t-lymphocyte antigen-4 (CTLA-4) antibody (or any other antibody targeting T cell co-stimulation pathways)
- Known history of Human Immunodeficiency Virus
- Active infection requiring therapy, positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA)
- Underlying medical conditions that will make the administration of study drug hazardous
- Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids
- Use of other investigational drugs (drugs not marketed for any indication) within 28 days or at least 5 half-lives (whichever is longer) before study drug administration
Opintosuunnitelma
Tässä osiossa on tietoja tutkimussuunnitelmasta, mukaan lukien kuinka tutkimus on suunniteltu ja mitä tutkimuksella mitataan.
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Ei satunnaistettu
- Inventiomalli: Yksittäinen ryhmätehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
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Kokeellinen: Melanoma - BMS-936558 (MDX-1106)
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Solution, Intravenous, 0.1 mg/kg - 10 mg/kg, Every 2 weeks, 3 years depending on response
Muut nimet:
Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
Muut nimet:
Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
Muut nimet:
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Kokeellinen: RCC - BMS-936558 (MDX-1106)
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Solution, Intravenous, 0.1 mg/kg - 10 mg/kg, Every 2 weeks, 3 years depending on response
Muut nimet:
Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
Muut nimet:
Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
Muut nimet:
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Kokeellinen: mCRPC - BMS-936558 (MDX-1106)
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Solution, Intravenous, 0.1 mg/kg - 10 mg/kg, Every 2 weeks, 3 years depending on response
Muut nimet:
Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
Muut nimet:
Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
Muut nimet:
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Kokeellinen: NSCLC - BMS-936558 (MDX-1106)
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Solution, Intravenous, 0.1 mg/kg - 10 mg/kg, Every 2 weeks, 3 years depending on response
Muut nimet:
Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
Muut nimet:
Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
Muut nimet:
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Kokeellinen: CRC - BMS-936558 (MDX-1106)
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Solution, Intravenous, 0.1 mg/kg - 10 mg/kg, Every 2 weeks, 3 years depending on response
Muut nimet:
Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
Muut nimet:
Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
Muut nimet:
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Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs
Aikaikkuna: Day 1 to 70 days following last dose of study drug up to June 2013, approximately 4 years
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AE=any new unfavorable symptom, sign or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity or drug dependency/abuse; is life-threatening, an important medical event or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible or missing relationship to study drug. Death=during the study and up to 28 days past study discontinuation. The select AEs were determined using the Medical Dictionary for Regulatory Activities (MedDRA, v15.1) and graded using the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0. |
Day 1 to 70 days following last dose of study drug up to June 2013, approximately 4 years
|
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Number of Participants With Abnormal Serum Chemistry Laboratory Values
Aikaikkuna: Day 1 up to June 2013, approximately 4 years
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Alkaline phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine and Total Bilirubin.
National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr).
Abnormal values for ALP, ALT and AST were based on grades; Gr 1: > 1.0 - 2.5 * upper limits of normal (ULN); Gr 2: > 2.5 - 5.0 * ULN; Gr 3: > 5.0 - 20.0 * ULN; Gr 4: > 20.0 * ULN.
Abnormal values for Creatinine were based on Gr 1: > 1.0 - 1.5*ULN; Gr 2: > 1.5 - 3.0*ULN; Gr 3: > 3.0 - 6.0*ULN; Gr 4: > 6.0*ULN.
Abnormal values for Total Bilirubin were based on Gr 1: > 1.0 - 1.5 * upper limits of normal (ULN); Gr 2: > 1.5 - 3.0 * ULN; Gr 3: > 3.0 - 10.0 * ULN; Gr 4: > 10.0 * ULN.
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Day 1 up to June 2013, approximately 4 years
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Number of Participants With Abnormal Hematology Laboratory Values
Aikaikkuna: Day 1 up to June 2013, approximately 4 years
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Hemoglobin, Lymphocytes, Neutrophils, Platelets and Leukocytes.
National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr).
Abnormal values for Hemoglobin were based on Gr 1: 10.0 - less than (<) lower limit of normal (LLN); Gr 2: 8.0 - < 10.0; Gr 3: 6.5 - < 8.0; Gr 4: < 6.5.
Abnormal values for Lymphocytes were based on Gr 1: 0.8 - < 1.5; Gr 2: 0.5 - < 0.8; Gr 3): 0.2 - < 0.5; Gr 4: < 0.2.
Abnormal values for Neutrophils were based on Gr 1: 1.5 - < 2.0; Gr 2: 1.0 - < 1.5; Gr 3: 0.5 - < 1.0; Gr 4: < 0.5.
Abnormal values for Platelets were based on Gr 1: 75.0 - < lower limits of normal (LLN); Gr 2: 50.0 - < 75.0;
Gr 3: 25.0 - < 50.0;
Gr 4: < 25.0.
Abnormal values for Leukocytes were based on Gr 1: 3.0 - < LLN; Gr 2: 2.0 - < 3.0; Gr 3: 1.0 - < 2.0; Gr4: < 1.0.
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Day 1 up to June 2013, approximately 4 years
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Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Immunogenicity Assessment
Aikaikkuna: Day 1 up to June 2013, approximately 4 years
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Classification of participants host immune response was based on the following definitions: Anti-Drug Antibody (ADA) Positive Subjects have with at least one ADA positive sample at any time after initiation of treatment.
ADA positive subjects were further classified into categories with Persistent Positive defined as an ADA positive sample at 2 or more sequential timepoints at least 8 weeks apart.
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Day 1 up to June 2013, approximately 4 years
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Objective Response Rate
Aikaikkuna: Day 1 up to June 2013, approximately 4 years
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Tumor response was evaluated by the sponsor based on tumor assessments by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.0.
Objective response rate (ORR) was defined as the proportion of participants who's confirmed best overall response (BOR) is either complete (CR) or partial (PR), where the denominator is the number of treated participants in the population of interest.
Response was based on tumor measurements.
Responders= complete response (CR) or partial response (PR).
CR=disappearance of all target and non-target lesions; PR=at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the screening sum longest diameter.
95% Confidence intervals (CIs) were computed using the Clopper Pearson method.
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Day 1 up to June 2013, approximately 4 years
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Duration of Tumor Response
Aikaikkuna: Day 1 up to June 2013, approximately 4 years
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Duration of tumor response (DOR) was calculated from the first date of response of complete response (CR) or partial response (PR) to the date of the first progressive disease (PD) or the date of death.
Duration of response was censored at the last tumor assessment date if a responder did not have PD or death.
Nonresponders were not included in the analysis.
Median DOR was estimated by Kaplan-Meier analysis.
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Day 1 up to June 2013, approximately 4 years
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Geometric Mean Maximum Serum Concentration (Cmax)
Aikaikkuna: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3
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Nivolumab in human serum was assayed by PPD® (Richmond, Virginia) using a cross-validated enzyme-linked immunosorbent assay (ELISA).
Blood samples were assessed at all doses from a subset of participants.
The pharmacokinetic (PK) parameter of Cmax was measured in micrograms per milliliter (µg/mL).
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1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3
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Median Time of Maximum Serum Concentration (Tmax)
Aikaikkuna: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3
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Nivolumab in human serum was assayed by PPD® (Richmond, Virginia) using a cross-validated ELISA.
Blood samples were assessed Blood samples were assessed at all doses from a subset of participants.
The PK parameter of Tmax was measured in hours (h).
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1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3
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Geometric Mean Area Under the Curve (AUC[TAU]) in One Dosing Interval Observed Post-Single Dose
Aikaikkuna: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3
|
Nivolumab in human serum was assayed by PPD® (Richmond, Virginia) using a cross-validated ELISA.
Blood samples were assessed at all doses from a subset of participants.
The PK parameter of AUC was measured in micrograms*hours per milliliter (μg*h/mL).
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1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3
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Geometric Mean Total Body Clearance of Drug From Serum (CLT)
Aikaikkuna: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycle 3
|
Nivolumab in human serum was assayed by PPD® (Richmond, Virginia) using a cross-validated ELISA.
Blood samples Blood samples were assessed at all doses from a subset of participants.
The PK parameter of CLT was measured in milliliters per hour (mL/h).
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1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycle 3
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Mean Effective Half-life (T-HALFeff)
Aikaikkuna: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycle 3
|
Nivolumab in human serum was assayed by PPD® (Richmond, Virginia) using a cross-validated ELISA.
Blood samples were assessed at all doses from a subset of participants.
The PK parameter of T-HALFeff was measured in hours (h).
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1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycle 3
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Yhteistyökumppanit ja tutkijat
Täältä löydät tähän tutkimukseen osallistuvat ihmiset ja organisaatiot.
Sponsori
Yhteistyökumppanit
Julkaisuja ja hyödyllisiä linkkejä
Tutkimusta koskevien tietojen syöttämisestä vastaava henkilö toimittaa nämä julkaisut vapaaehtoisesti. Nämä voivat koskea mitä tahansa tutkimukseen liittyvää.
Yleiset julkaisut
- Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Drilon A, Wolchok JD, Carvajal RD, McHenry MB, Hosein F, Harbison CT, Grosso JF, Sznol M. Five-Year Survival and Correlates Among Patients With Advanced Melanoma, Renal Cell Carcinoma, or Non-Small Cell Lung Cancer Treated With Nivolumab. JAMA Oncol. 2019 Oct 1;5(10):1411-1420. doi: 10.1001/jamaoncol.2019.2187.
- Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, Leming PD, Lipson EJ, Puzanov I, Smith DC, Taube JM, Wigginton JM, Kollia GD, Gupta A, Pardoll DM, Sosman JA, Hodi FS. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014 Apr 1;32(10):1020-30. doi: 10.1200/JCO.2013.53.0105. Epub 2014 Mar 3.
- Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012 Jun 28;366(26):2443-54. doi: 10.1056/NEJMoa1200690. Epub 2012 Jun 2.
Opintojen ennätyspäivät
Nämä päivämäärät seuraavat ClinicalTrials.gov-sivustolle lähetettyjen tutkimustietueiden ja yhteenvetojen edistymistä. National Library of Medicine (NLM) tarkistaa tutkimustiedot ja raportoidut tulokset varmistaakseen, että ne täyttävät tietyt laadunvalvontastandardit, ennen kuin ne julkaistaan julkisella verkkosivustolla.
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Torstai 30. lokakuuta 2008
Ensisijainen valmistuminen (Todellinen)
Maanantai 4. helmikuuta 2013
Opintojen valmistuminen (Todellinen)
Tiistai 22. joulukuuta 2020
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Maanantai 4. elokuuta 2008
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Torstai 7. elokuuta 2008
Ensimmäinen Lähetetty (Arvio)
Perjantai 8. elokuuta 2008
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Perjantai 3. joulukuuta 2021
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Keskiviikko 1. joulukuuta 2021
Viimeksi vahvistettu
Maanantai 1. marraskuuta 2021
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Muita asiaankuuluvia MeSH-ehtoja
- Neoplasmat histologisen tyypin mukaan
- Neoplasmat
- Urologiset kasvaimet
- Urogenitaaliset kasvaimet
- Neoplasmat sivustoittain
- Munuaissairaudet
- Urologiset sairaudet
- Adenokarsinooma
- Karsinooma
- Kasvaimet, rauhas- ja epiteelikasvaimet
- Munuaisten kasvaimet
- Karsinooma, munuaissolut
- Farmakologisen vaikutuksen molekyylimekanismit
- Antineoplastiset aineet
- Antineoplastiset aineet, immunologiset
- Immuunijärjestelmän tarkistuspisteen estäjät
- Nivolumabi
Muut tutkimustunnusnumerot
- CA209-003
- MDX1106-03 (Muu tunniste: BMS)
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Joo
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Nämä tiedot haettiin suoraan verkkosivustolta clinicaltrials.gov ilman muutoksia. Jos sinulla on pyyntöjä muuttaa, poistaa tai päivittää tutkimustietojasi, ota yhteyttä register@clinicaltrials.gov. Heti kun muutos on otettu käyttöön osoitteessa clinicaltrials.gov, se päivitetään automaattisesti myös verkkosivustollemme .