A Study On An Immunostimulant Antibody In Combination With Chemotherapy For Advanced Cancer Of The Pancreas
26 novembre 2013 mis à jour par: Hoffmann-La Roche
A Phase 1 Dose Escalation Open Label Study Of CP-870,893 In Combination With Gemcitabine In Patients With Chemotherapy-Naïve Surgically Incurable Pancreatic Cancer
This study aims to seek evidence that activation of certain cells of the immune system will be safe and well tolerated in combination with cytotoxic chemotherapy.
Preliminary evidence of clinical anti-tumor activity will be sought.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Type d'étude
Interventionnel
Inscription (Réel)
22
Phase
- La phase 1
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Indiana
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Indianapolis, Indiana, États-Unis, 46202
- Pfizer Investigational Site
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Pennsylvania
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Philadelphia, Pennsylvania, États-Unis, 19104
- Pfizer Investigational Site
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-
Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
Inclusion Criteria:
- 1st-line surgically incurable cancer of the pancreas
- ECOG(Eastern Cooperative Oncology Group) performance status 0-1
Exclusion Criteria:
- Previous systemic therapy for pancreas cancer
- History of cancer-associated blood clots
- History of autoimmune disease
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Non randomisé
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: bras unique
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CP-870,893 intravenous administration [IV] on day 3 of 4-week cycles
gemcitabine 1000 mg/m^2 intravenous administration [IV] q week [wk]x3 of 4-week cycles
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Number of Participants With Dose Limiting Toxicities (DLTs)
Délai: Baseline up to Cycle 1 / Day 28
|
Any of the following during first cycle of treatment and attributable to CP-870893: afebrile Grade (Gr) 4 neutropenia (absolute neutrophil count [ANC] <500 cells/mm^3) ≥7 days or Gr 3 or 4 neutropenia associated with fever (1 oral temperature >38.5 degrees Celsius (C) or 3 oral temperatures >38.0 degrees C in a 24-hour period); Gr 4 thrombocytopenia or Gr 3 thrombocytopenia associated with bleeding; Gr 4 lymphopenia, if coupled with clinical consequence (such as, opportunistic infection) or any other Gr 3 hematological adverse events; ≥Gr 3 non-hematologic toxicities (except alopecia). |
Baseline up to Cycle 1 / Day 28
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Percentage of Participants With Objective Tumor Response According to Response Evaluation Criteria in Solid Tumors (RECIST)
Délai: At the end of every even-numbered cycle (cycle=28 days) up to a maximum of 12 cycles and 4 to 6 weeks following initial documentation of response
|
Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST.
Confirmed CR defined as disappearance of all target lesions.
Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST.
Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.
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At the end of every even-numbered cycle (cycle=28 days) up to a maximum of 12 cycles and 4 to 6 weeks following initial documentation of response
|
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Overall Survival (OS)
Délai: Baseline, assessed monthly until death or 7.5 months after last participant was enrolled (up to January 2011)
|
OS is time from baseline to death from any cause.
Participants last known to be alive were censored at the date of last contact.
|
Baseline, assessed monthly until death or 7.5 months after last participant was enrolled (up to January 2011)
|
|
Progression Free Survival (PFS)
Délai: Baseline, assessed monthly until death or 7.5 months after last participant was enrolled (up to January 2011)
|
PFS is time from baseline to first progression (Prog) or death from any cause.
Participants last known to be alive, had not started a new (non-protocol) cancer treatment, were Prog-free, and who had a baseline and ≥1 on-study disease assessment were censored at date of last objective disease assessment that verified lack of Prog.
Participants who were off treatment prior to Prog and who had no on-study disease assessment were also censored.
Prog: ≥20% increase in sum of longest dimension (LD) of target lesions from smallest sum LD recorded since treatment start or appearance of ≥1 new lesions.
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Baseline, assessed monthly until death or 7.5 months after last participant was enrolled (up to January 2011)
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Time to Progression
Délai: Monthly until death or 7.5 months after last participant was enrolled (up to January 2011)
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Disease progression defined as ≥20% increase in sum LD of target lesions from smallest sum LD recorded since treatment start or appearance of ≥1 new lesions.
Criteria for progression also included unequivocal progression of existing nontarget lesions.
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Monthly until death or 7.5 months after last participant was enrolled (up to January 2011)
|
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Maximum Serum Concentration (Cmax)
Délai: Cycle 1 / Day 3 pre-dose, 5 minutes after End of Infusion (EOI), and 2, 6, and 24 hours after EOI and pre-dose on Day 3 of every subsequent cycle up to a maximum of 12 cycles
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Cycle 1 / Day 3 pre-dose, 5 minutes after End of Infusion (EOI), and 2, 6, and 24 hours after EOI and pre-dose on Day 3 of every subsequent cycle up to a maximum of 12 cycles
|
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Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Délai: Cycle 1 / Day 3 pre-dose, 5 minutes after EOI, and 2, 6, and 24 hours after EOI and pre-dose on Day 3 of every subsequent cycle up to a maximum of 12 cycles
|
Area under the serum concentration time-curve from time zero to the last measured concentration.
AUClast analyzed using a noncompartmental approach to estimate individual participant values.
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Cycle 1 / Day 3 pre-dose, 5 minutes after EOI, and 2, 6, and 24 hours after EOI and pre-dose on Day 3 of every subsequent cycle up to a maximum of 12 cycles
|
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Change (Pre-dose to Post-dose) in Plasma Cytokine Concentrations: Pre-dose Concentration (CYTO0), Maximum Concentration (CTYOMAX)
Délai: Cycle 1 / Day 1 prior to gemcitabine infusion (0 hour), 5 minutes after EOI and 2, 4, 6, and 24 hours after EOI; Cycle 1 / Day 3 prior to CP-970893 infusion (0 hour), 5 minutes after EOI, and 2, 4, 6, and 24 hours after EOI
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An increase in values indicates greater cytokine release from cells targeted by the antibody and may be associated with an infusion reaction.
Change calculated as mean of pre-dose and maximum post-dose values.
|
Cycle 1 / Day 1 prior to gemcitabine infusion (0 hour), 5 minutes after EOI and 2, 4, 6, and 24 hours after EOI; Cycle 1 / Day 3 prior to CP-970893 infusion (0 hour), 5 minutes after EOI, and 2, 4, 6, and 24 hours after EOI
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Change (Pre-dose to Post-dose) in Plasma Cytokine Concentrations: Time of Maximum Concentration (TCYTOMAX)
Délai: Cycle 1 / Day 1 prior to gemcitabine infusion (0 hour), 5 minutes after EOI and 2, 4, 6, and 24 hours after EOI; Cycle 1 / Day 3 prior to CP-970893 infusion (0 hour), 5 minutes after EOI, and 2, 4, 6, and 24 hours after EOI
|
An increase in values indicates greater cytokine release from cells targeted by the antibody and may be associated with an infusion reaction.
Change calculated as mean of pre-dose and maximum post-dose values.
|
Cycle 1 / Day 1 prior to gemcitabine infusion (0 hour), 5 minutes after EOI and 2, 4, 6, and 24 hours after EOI; Cycle 1 / Day 3 prior to CP-970893 infusion (0 hour), 5 minutes after EOI, and 2, 4, 6, and 24 hours after EOI
|
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Total and Neutralizing Human Antihuman Antibody (HAHA) Titer
Délai: Prior to infusion of CP-870893 on Day 3 of every cycle up to a maximum of 12 cycles
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HAHA assessed as an indicator of immunogenicity to CP-870893.
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Prior to infusion of CP-870893 on Day 3 of every cycle up to a maximum of 12 cycles
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Change (Pre-dose to Post-dose) in Bone Marrow Derived Cells (B Cell) Surface Markers: CD54, CD23, CD40, CD86, and Human Leukocyte Antigen (HLA-DR)
Délai: Cycle 1 / Day 1 and Cycle 1 / Day 8 prior to gemcitabine infusion and 6 and 24 hours after EOI; Cycle 1 / Day 3 prior to CP-870893 infusion and 6, 24, and 48 hours after EOI
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Assess the ability of PF-870893 to activate B-cells and HLA-DR which are involved in the production of antibodies.
Change calculated as mean of pre-dose and post-dose values.
Positive values indicate greater presence of cells associated with antibody production.
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Cycle 1 / Day 1 and Cycle 1 / Day 8 prior to gemcitabine infusion and 6 and 24 hours after EOI; Cycle 1 / Day 3 prior to CP-870893 infusion and 6, 24, and 48 hours after EOI
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18-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) Imaging (MTD Expansion Cohort)
Délai: Baseline, Week 2, Week 8, and Single Time Point (STP) PET for all PET scans after Week 8
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FDG PET assessment to characterize and monitor tumors before and after study treatment; measured as a standardized uptake value (SUV).
A reduction in SUV from baseline for at least 1 tumor may indicate a positive metabolic response to treatment.
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Baseline, Week 2, Week 8, and Single Time Point (STP) PET for all PET scans after Week 8
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Carbohydrate Antigen 19-9 (CA 19-9)
Délai: At the end of every even-numbered cycle (cycle=28 days) and 4 to 6 weeks following initial documentation of response
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CA 19-9 or sialylated Lewis (a) antigen (a tumor marker).
Values higher than 37 units per milliliter (U/ml) considered abnormal; higher values usually indicate greater presence of disease.
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At the end of every even-numbered cycle (cycle=28 days) and 4 to 6 weeks following initial documentation of response
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Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Recommended Phase 2 Dose (RP2D) of CP-870893 in Participants With Advanced Pancreas Cancer
Délai: Baseline up to time of determination of maximum tolerated dose (MTD)
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Additional participants enrolled at MTD of CP-870893 to further characterize suitability for phase 2 testing.
RP2D confirmed if ≤ 3 our of 12 participants in expansion cohort experience DLT in cycle 1.
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Baseline up to time of determination of maximum tolerated dose (MTD)
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
Publications et liens utiles
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Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 juin 2008
Achèvement primaire (Réel)
1 janvier 2011
Achèvement de l'étude (Réel)
1 janvier 2011
Dates d'inscription aux études
Première soumission
26 juin 2008
Première soumission répondant aux critères de contrôle qualité
7 juillet 2008
Première publication (Estimation)
8 juillet 2008
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
24 décembre 2013
Dernière mise à jour soumise répondant aux critères de contrôle qualité
26 novembre 2013
Dernière vérification
1 novembre 2013
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- A5021005
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Non
Étudie un produit d'appareil réglementé par la FDA américaine
Non
produit fabriqué et exporté des États-Unis.
Non
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .