Clinical Trials /

A First-in-human Phase Ia/b, Open Label, Multicentre, Dose Escalation Study of BI 905711 in Patients With Advanced Gastrointestinal Cancers

NCT04137289

Description:

Phase Ia - Explore safety and establish the maximum tolerated dose (MTD)/recommended dose levels for phase Ib expansion phase of BI 905711 based on the frequency of patients experiencing dose limiting toxicities (DLTs) during the MTD evaluation period. The MTD evaluation period is defined as the first two treatment cycles (from first dose administration until the day preceding the third dose administration or end of REP in case of discontinuation before start of Cycle 3). Phase Ia - Explore pharmacokinetics/pharmacodynamics, and efficacy to guide the determination of a potentially effective dose range for phase Ib in the absence of MTD. Phase Ib - Evaluate efficacy and safety of BI 905711 at a potentially effective dose range and determine the Recommended Phase 2 Dose (RP2D)

Related Conditions:
  • Cholangiocarcinoma
  • Colorectal Adenocarcinoma
  • Esophageal Adenocarcinoma
  • Gallbladder Carcinoma
  • Gastric Adenocarcinoma
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A First-in-human Phase Ia/b, Open Label, Multicentre, Dose Escalation Study of BI 905711 in Patients With Advanced Gastrointestinal Cancers
  • Official Title: A First-in-human Phase Ia/b, Open Label, Multicentre, Dose Escalation Study of BI 905711 in Patients With Advanced Gastrointestinal Cancers

Clinical Trial IDs

  • ORG STUDY ID: 1412-0001
  • SECONDARY ID: 2018-003268-29
  • NCT ID: NCT04137289

Conditions

  • Gastrointestinal Neoplasms
  • Cholangiocarcinoma
  • Pancreatic Neoplasms

Interventions

DrugSynonymsArms
BI 905711BI 905711

Purpose

Phase Ia - Explore safety and establish the maximum tolerated dose (MTD)/recommended dose levels for phase Ib expansion phase of BI 905711 based on the frequency of patients experiencing dose limiting toxicities (DLTs) during the MTD evaluation period. The MTD evaluation period is defined as the first two treatment cycles (from first dose administration until the day preceding the third dose administration or end of REP in case of discontinuation before start of Cycle 3). Phase Ia - Explore pharmacokinetics/pharmacodynamics, and efficacy to guide the determination of a potentially effective dose range for phase Ib in the absence of MTD. Phase Ib - Evaluate efficacy and safety of BI 905711 at a potentially effective dose range and determine the Recommended Phase 2 Dose (RP2D)

Trial Arms

NameTypeDescriptionInterventions
BI 905711Experimental
  • BI 905711

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically confirmed, advanced unresectable or metastatic
             gastrointestinal cancers of following histologies:

               -  Colorectal adenocarcinoma

               -  Gastric adenocarcinoma

               -  Esophageal adenocarcinoma

               -  Pancreatic adenocarcinoma

               -  Cholangiocarcinoma

          -  Patient who has failed all available conventional therapies known to confer clinical
             benefit for their disease based on local approved standards. For patients with
             colorectal cancer, prior treatment with regorafenib or TAS-102 is optional.

          -  Phase Ia (dose escalation) only: Patient with either measurable or
             non-measurable/non-evaluable disease.

          -  Phase Ia (expanded cohort) and Phase Ib (expansion phase) only: At least one target
             lesion that can be accurately measured per RECIST v.1.1

          -  Availability and willingness to undergo tumor biopsy before treatment to provide tumor
             tissue. Pre-treatment fresh tumor biopsy collections for biomarker analyses are
             considered optional in phase Ia and mandatory in phase Ib. However, fresh tumor
             biopsies will NOT be considered if significant risk procedures are required including
             (but not limited to) biopsies of the pancreas, or endoscopic procedures extending
             beyond the esophagus, stomach or bowel. Only non-significant risk procedures per the
             investigator's judgment will be used to obtain any biopsies specified in this study.
             In case a fresh tumor biopsy cannot be obtained due to before mentioned reasons an
             archived tumor tissue specimen needs to be submitted.

          -  Adequate hepatic, renal and bone marrow functions as defined by all of the below:

               -  Total bilirubin (= 1.5 x institutional ULN (= 3 x institutional ULN for patient
                  with Gilbert's syndrome)

               -  ALT and AST =2.5 x institutional ULN (=5 x institutional ULN for patients with
                  known liver metastases)

               -  Serum creatinine =1.5x institutional ULN. If creatinine is > 1.5 x ULN, patient
                  is eligible if concurrent creatinine clearance = 50 ml/min (measured or
                  calculated by CKD-EPI formula or Japanese version of CKD-EPI formula for Japanese
                  patients).

               -  ANC = 1.0x 10^9/L

               -  Platelets = 100x10^9/ L

               -  Hb =9.0 g/dl (without transfusion within previous week)

               -  Serum lipase = 1.5 institutional ULN

          -  Recovery from any adverse events of previous anti-cancer therapies to baseline or
             CTCAE grade 1, except for alopecia CTCAE grade 2, sensory peripheral neuropathy CTCAE
             grade = 2 or considered not clinically significant.

          -  ECOG performance status = 1

          -  Life expectancy = 3 months in the opinion of the investigator

          -  Of legal adult age (according to local legislation) at screening

          -  Signed and dated written informed consent in accordance with ICH-GCP and local
             legislation prior to admission to the trial.

          -  Male or female patients. Women of childbearing potential (WOCBP) and men able to
             father a child must be ready and able to use highly effective methods of birth control
             per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used
             consistently and correctly.

        Exclusion Criteria:

          -  Treatment with a systemic anti-cancer therapy or investigational drug within 14 days
             or 5 half-lives (whichever is shorter) of the first treatment with the study
             medication.

          -  Radiation therapy with extensive large field involving parenchymal organs in chest,
             abdomen or pelvis within 3 weeks of the first treatment in the study. There is no
             restriction for minor small field radiotherapy.

          -  Any history of or concomitant condition that, in the opinion of the investigator,
             would compromise the patient's ability to comply with the study or interfere with the
             evaluation of the safety or efficacy of the test drug.

          -  Known pathological condition of GI tract, liver and pancreas, excluding the disease
             under study, that may interfere with assessment of drug safety or may increase the
             risk of toxicity:

               -  inflammatory bowel disease

               -  chronic pancreatitis

               -  other serious GI pathological conditions by judgment of the investigator e.g.
                  autoimmune disease with GI involvement, unexplained active diarrhea CTCAE grade
                  =2

          -  Known history of human immunodeficiency virus infection.

          -  Any of the following laboratory evidence of hepatitis virus infection. Test results
             obtained in routine diagnostics are acceptable if done within 14 days before the
             informed consent date:

               -  Positive results of hepatitis B surface (HBs) antigen

               -  Presence of HBc antibody together with HBV-DNA

               -  Presence of hepatitis C RNA

          -  Active concomitant malignancies, other than the one treated in this trial.

          -  Patients who require anticoagulation therapy with heparin or low molecular weight
             heparin (LMWH). Therapy with factor Xa inhibitors, direct thrombin inhibitors, and
             warfarin is allowed. Patients receiving warfarin must have their INR values closely
             monitored according to institutional guidelines.

          -  Chronic alcohol or drug abuse or any condition that, in the investigator's opinion,
             makes the patient an unreliable trial participant or unlikely to comply with the
             protocol requirements or not expected to complete the trial as scheduled.

          -  Women who are pregnant, nursing, or who plan to become pregnant while in the trial;
             female patients who do not agree to the interruption of breast feeding from the start
             of study treatment to within 30 days after the last study treatment.

          -  Presence of uncontrolled or symptomatic brain or subdural metastases. Inclusion of
             patients with brain metastases who have completed local therapy and are considered
             stable by the investigator, or with newly identified asymptomatic brain metastases at
             screening will be allowed. Use of corticosteroids is allowed if the dose was stable
             for at least 1 week before the baseline MRI.

          -  Patients who are under judicial protection and patients who are legally
             institutionalized

          -  Major surgery (major according to the investigator's assessment) performed within 3
             weeks prior to treatment start or planned within 3 months after screening, e.g. hip
             replacement.

          -  Any of the following cardiac criteria:

               -  Mean resting corrected QT interval (QTc) >470 msec

               -  Any clinically important abnormalities (as assessed by the Investigator) in
                  rhythm, conduction, or morphology of resting ECGs, e.g., complete left bundle
                  branch block, third degree heart block

               -  Patients with an ejection fraction (EF) <50% or the lower limit of normal of the
                  institutional standard will be excluded. Only in cases where the Investigator (or
                  the treating physician or both) suspects cardiac disease with negative effect on
                  the EF, will the EF be measured during screening using an appropriate method
                  according to local standards to confirm eligibility (e.g., echocardiogram,
                  multi-gated acquisition scan). A historic measurement of EF no older than 6
                  months prior to first administration of study drug can be accepted provided that
                  there is clinical evidence that the EF value has not worsened since this
                  measurement in the opinion of the Investigator or of the treating physician or
                  both.

          -  Known hypersensitivity to the trial medication and/or its components i.e. polysorbate
             20, sodium citrate, lysine hydrochloride, sucrose, citric acid.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase Ia - Maximum tolerated dose (MTD) defined as the highest dose with less than 25% risk of the true DLT rate being equal or above 33% during the MTD evaluation period
Time Frame:Up to 28 days
Safety Issue:
Description:Objective response is defined as best overall response of complete response or partial response, where best overall response is the best response recorded from the start of the study treatment until the earliest of disease progression, death or last evaluable tumor assessment and before start of subsequent anti-cancer therapy

Secondary Outcome Measures

Measure:Phase Ia - Cmax: maximum measured concentration of BI 905711 in plasma
Time Frame:Up to day 1 and up to day 19
Safety Issue:
Description:
Measure:Phase Ia - AUC0-t2: area under the concentration-time curve of BI 905711 in plasma
Time Frame:Up to day 1 and up to day 19
Safety Issue:
Description:
Measure:Phase Ia - Objective response based on RECIST 1.1 criteria in patients with measurable disease
Time Frame:Up to 107 days
Safety Issue:
Description:
Measure:Phase Ib - Radiological (CT Scan) tumor shrinkage, defined as the difference between the minimum post-baseline sum of longest diameters of target lesions and the baseline sum of longest diameters of the same set of target lesions according to RECIST 1.1
Time Frame:Up to 107 days
Safety Issue:
Description:
Measure:Phase Ib -The duration of overall response is measured from the time measurement criteria are first met for CR/PR until the first date that recurrent or progressive disease is objectively documented according to RECIST 1.1
Time Frame:Up to 107 days
Safety Issue:
Description:
Measure:Phase Ib - Progression-free survival (PFS) is defined as the time from first treatment administration until tumor progression according to RECIST 1.1 or death from any cause, whichever occurs earlier
Time Frame:Up to 107 days
Safety Issue:
Description:
Measure:Phase Ib - Disease control, defined as CR, PR, or stable disease according to RECIST 1.1 from the start of treatment until the earliest of progression disease, death or last evaluable tumor assessment and before start of subsequent anti-cancer therapy
Time Frame:Baseline and up to 107 days
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Boehringer Ingelheim

Last Updated

June 3, 2020