Testing the Addition of an Anti-cancer Drug, Copanlisib, to the Usual Immunotherapy (Nivolumab With or Without Ipilimumab) in Patients With Advanced Solid Cancers That Have Changes in the Following Genes: PIK3CA and PTEN

Titre officiel

A Phase I/II Biomarker Driven Combination Trial of Copanlisib and Immune Checkpoint Inhibitors in Patients With Advanced Solid Tumours

Sommaire:

Cet essai de phase I/II vise à déterminer la dose optimale de copanlisib administré en association avec le nivolumab et l’ipilimumab, ainsi qu’à évaluer les effets secondaires et l’efficacité de ce traitement d’association chez des patients atteints de tumeurs solides qui se sont propagées à d’autres parties de l’organisme (stade avancé) et qui présentent des mutations dans les gènes PIK3CA et PTEN. Le copanlisib pourrait freiner la croissance des cellules tumorales en bloquant certaines enzymes nécessaires à la croissance cellulaire. L’immunothérapie au moyen d’anticorps monoclonaux, comme le nivolumab et l’ipilimumab, peut aider le système immunitaire de l’organisme à attaquer le cancer et entraver la capacité des cellules tumorales à croître et à se propager. L’ajout du copanlisib à l’immunothérapie habituelle pourrait donner de meilleurs résultats que l’immunothérapie habituelle seule chez des patients présentant des tumeurs solides.

Description de l'essai

Primary Outcome:

• Incidence of adverse events and serious adverse events
• Incidence of dose limiting toxicities (DLTs)

• Objective response (OR) rate (complete response [CR] + partial response [PR])
• Clinical benefit rate (OR + stable disease [SD] > 6 months)
• Progression free survival (PFS)
• Overall survival (OS)

PRIMARY OBJECTIVE:

• To evaluate safety and confirm the combination recommended phase 2 dose (RP2D) of the combination of copanlisib, nivolumab (and ipilimumab) in patients with molecularly-selected advanced solid tumours.

SECONDARY OBJECTIVES:

• To observe and record antitumor activity. II. To assess clinical benefit of copanlisib in combination with nivolumab (and ipilimumab) in patients with molecularly-selected advanced solid tumours, as measured by objective response (OR) = complete response (CR) + partial response (PR).
• To assess overall duration of response (DoR), progression free survival (PFS), and overall survival (OS).
• To assess immune-modulatory changes associated with copanlisib-induced PI3K inhibition and combination of copanlisib and nivolumab (and ipilimumab).
• To correlate molecular alterations in the PI3K-AKT pathway and treatment induced immune-modulatory changes with objective response (OR).

EXPLORATORY OBJECTIVES:

• To perform molecular profiling assays on malignant and normal tissues, including, but not limited to, whole exome sequencing (WES), ribonucleic acid (RNA) sequencing, reverse phase protein array (RPPA), circulating tumour deoxyribonucleic acid (DNA) analysis, and immune profiling in order to:
  
  • Identify potential predictive and prognostic biomarkers beyond any genomic alteration by which treatment may be assigned.
  • Identify resistance mechanisms using genomic DNA- and RNA-based assessment platforms.

• To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research.
• To bank formalin-fixed, paraffin-embedded (FFPE) tissue, blood (for cell-free DNA analysis), and nucleic acids obtained from patients at the Experimental Therapeutics Clinical Trials Network (ETCTN) Biorepository at Nationwide Children's Hospital.

OUTLINE: This is a phase I, dose-escalation study of copanlisib followed by a phase II study. Patients are assigned to 1 of 2 trials.

TRIAL I: Patients receive copanlisib hydrochloride intravenously (IV) over 1 hour on days 1, 8, and 15 of cycle 1. Beginning in cycle 2, patients also receive nivolumab IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

TRIAL II: Patients receive copanlisib hydrochloride IV over 1 hour on days 1, 8, and 15 of cycle 1. Beginning in cycle 2, patients also receive nivolumab IV over 60 minutes on day 1 and ipilimumab IV over 90 minutes every 8 weeks for 4 doses. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3-6 months for up to 2 years.

Voir cet essai sur ClinicalTrials.gov