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NCT02631590

Copanlisib (BAY 80-6946) in Combination With Gemcitabine and Cisplatin in Advanced Cholangiocarcinoma

Completed Phase 2 Results posted Last updated 4 August 2021
What this trial tests

Phase 2 trial testing Cisplatin in Biliary Carcinoma in 24 participants. Completed in 5 March 2021.

Timeline
5 July 2016
Primary endpoint
25 October 2019
5 March 2021

Quick facts

Lead sponsorH. Lee Moffitt Cancer Center and Research Institute
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment24
Start date5 July 2016
Primary completion25 October 2019
Estimated completion5 March 2021
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Who can join

18 and older, any sex, with Biliary Carcinoma or Gall Bladder Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression Free Survival (PFS) Primary · 6 months

PFS at six months. Response and progression will be evaluated using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1). PFS will be calculated from study entry to documented disease progression, death from any cause, or date of last follow-up, whichever comes first. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of

GroupValue95% CI
Combination Therapy6.22.9 – 10.1
Response Rate Secondary · Up to 24 months

Complete Response + Partial Response according to RECIST 1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Partial Response
GroupValue95% CI
Combination Therapy31.6
Stable Disease
GroupValue95% CI
Combination Therapy57.9
Overall Survival (OS) Secondary · Up to 24 months

The length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that patients diagnosed with the disease are still alive.

GroupValue95% CI
Combination Therapy13.76.8 – 18.0

Adverse events — posted to ClinicalTrials.gov

Time frame: All adverse events collected from start of study drug to 4 weeks after end of treatment, 2 years 3 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Combination Therapy
Serious: 12/24 (50%)
Deaths: 18/24

Serious adverse events (26 terms)

ReactionSystemCombination Therapy
Abdominal PainGastrointestinal disorders
AscitesGastrointestinal disorders
SepsisInfections and infestations
Blood bilirubin increasedInvestigations
AnemiaBlood and lymphatic system disorders
ColitisGastrointestinal disorders
Colonic obstructionGastrointestinal disorders
DysphagiaGastrointestinal disorders
Gastrointestinal disorders -OtherGastrointestinal disorders
NauseaGastrointestinal disorders
Edema limbsGeneral disorders
FatigueGeneral disorders
PainGeneral disorders
CholecystitisHepatobiliary disorders
Gallbladder obstructionHepatobiliary disorders
Hepatic infectionHepatobiliary disorders
Infections and Infestations - OtherInfections and infestations
Lung infectionInfections and infestations
Urinary tract infectionInfections and infestations
Platelet count decreasedInvestigations
AnorexiaMetabolism and nutrition disorders
DehydrationMetabolism and nutrition disorders
Neoplasms benign, malignant and unspecified - OtherNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Urinary tract obstructionRenal and urinary disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Other adverse events (123 terms — click to expand)

ReactionSystemCombination Therapy
Lymphocyte count decreasedInvestigations
Platelet count decreasedInvestigations
FatigueGeneral disorders
White blood cell decreasedInvestigations
Neutrophil count decreasedInvestigations
AnemiaBlood and lymphatic system disorders
HypertensionVascular disorders
HyperglycemiaMetabolism and nutrition disorders
NauseaGastrointestinal disorders
DiarrheaGastrointestinal disorders
Lipase increasedInvestigations
AnorexiaMetabolism and nutrition disorders
Abdominal PainGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
FeverGeneral disorders
HyponatremiaMetabolism and nutrition disorders
ConstipationGastrointestinal disorders
VomitingGastrointestinal disorders
Weight lossInvestigations
DehydrationMetabolism and nutrition disorders
HyperkalemiaMetabolism and nutrition disorders
HypotensionVascular disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
Edema limbsGeneral disorders
Aspartate aminotransferase increasedInvestigations
Serum amylase increasedInvestigations
ChillsGeneral disorders
PainGeneral disorders
Alkaline phosphatase increasedInvestigations
Creatinine increasedInvestigations
Thromboembolic eventVascular disorders
DizzinessNervous system disorders
Sinus tachycardiaCardiac disorders
Gastrointestinal disorders - OtherGastrointestinal disorders
Mucositis oralGastrointestinal disorders
Infusion related reactionGeneral disorders
Non-cardiac chest painGeneral disorders
Blood bilirubin increasedInvestigations
HypoalbuminemiaMetabolism and nutrition disorders
DyspneaRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Abdominal Pain, Ascites, Sepsis, Blood bilirubin increased, Anemia, Colitis, Colonic obstruction, Dysphagia.

Data from ClinicalTrials.gov NCT02631590 adverse events section.

Sponsor's own description

The purpose of this study is to see if an experimental drug, called copanlisib is effective and safe in treating adult participants with cholangiocarcinoma, when used in combination with gemcitabine and cisplatin.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting PI3K in cancer: mechanisms and advances in clinical trials.
    Yang J, Nie J, Ma X, Wei Y, et al · · 2019 · cited 1142× · PMID 30782187 · DOI 10.1186/s12943-019-0954-x
  2. New Horizons for Precision Medicine in Biliary Tract Cancers.
    Valle JW, Lamarca A, Goyal L, Barriuso J, et al · · 2017 · cited 475× · PMID 28818953 · DOI 10.1158/2159-8290.cd-17-0245
  3. Biliary tract cancers: current knowledge, clinical candidates and future challenges.
    Tariq NU, McNamara MG, Valle JW. · · 2019 · cited 79× · PMID 31015767 · DOI 10.2147/cmar.s157092
  4. Therapy of Primary Liver Cancer.
    Feng M, Pan Y, Kong R, Shu S. · · 2020 · cited 71× · PMID 32914142 · DOI 10.1016/j.xinn.2020.100032
  5. Targeted Therapies in Cholangiocarcinoma: Emerging Evidence from Clinical Trials.
    Simile MM, Bagella P, Vidili G, Spanu A, et al · · 2019 · cited 58× · PMID 30743998 · DOI 10.3390/medicina55020042
  6. Targeted Therapies in Advanced Biliary Tract Cancer: An Evolving Paradigm.
    Chakrabarti S, Kamgar M, Mahipal A. · · 2020 · cited 48× · PMID 32722188 · DOI 10.3390/cancers12082039
  7. Biliary tract cancer: current challenges and future prospects.
    Ghidini M, Pizzo C, Botticelli A, Hahne JC, et al · · 2019 · cited 47× · PMID 30643463 · DOI 10.2147/cmar.s157156
  8. Gallbladder cancer: review of a rare orphan gastrointestinal cancer with a focus on populations of New Mexico.
    Nemunaitis JM, Brown-Glabeman U, Soares H, Belmonte J, et al · · 2018 · cited 43× · PMID 29914418 · DOI 10.1186/s12885-018-4575-3

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