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Completed

NCT Number: NCT01403974

Phase I Trial of BI 836845 for Various Solid Cancer

This study is a phase I, open-label, dose escalation trial to determine the maximum tolerated dose (MTD) or the relevant biological dose (RBD) in the absence if a MTD of a new drug BI 836845 which blocks the insulin-like growth factor (IGF) pathway believed to be involved in cancer growth. BI 836845 will be administered for the very first time into cancer patients.

The study will also look at the overall safety of the drug, and examine the drug levels in the body at specific timepoints during the trial (pharmacokinetic profile); the effect the drug may have on tumours will also be examined (pharmacodynamics).

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Key information

Conditions

Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

China Medical University Hospital, Taichung, Taiwan

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients with histologically or cytologically confirmed diagnosis of advanced, non resectable and / or metastatic solid cancer, who have failed conventional treatment, or for whom no therapy of proven efficacy exists, or who are not amenable to established forms of treatment.
  • Patients should have evaluable disease, or at least one measurable lesion according to RECIST criteria version 1.1.
  • Age 18 years or older.
  • Life expectancy of at least 3 months in the opinion of the investigator.
  • Written informed consent that is consistent with ICH-GCP guidelines and local legislation.
  • Eastern Cooperative Oncology Group (ECOG) performance score 0, 1 or 2.
  • Patients must have recovered from any previous surgery and have had no major surgery within the last 28 days prior to start of trial medication in the opinion of the investigator.
  • Cardiac left ventricular function with resting ejection fraction > 50% as determined by ECHO or MUGA.
  • Absolute neutrophil count = 1,500/µL.
  • Platelets =100,000/µL.
  • Total bilirubin = 1.5x institution ULN.
  • AST and ALT = 2.5x institution ULN (in case of hepatic primary cancer or known liver metastases: AST and ALT = 5x ULN).
  • Creatinine =1.5 x institution ULN.
  • Haemoglobin = 9g/dL.
  • Haemoglobin A1c less than 8% and fasting plasma glucose =160 mg/dL (=8.9 mmol/L).
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) for the duration of trial participation. Female patients with reproductive potential must have a negative serum pregnancy test within 7 days of trial enrolment.
  • Child-Pugh score 5 or 6. (this criterion is limited to HCC patients in Part II only).
  • Patients eligible to undergo tumor biopsy should have normal coagulation parameters (INR and PTT within normal range). (this criterion is limited to patients in Part II only)

Exclusion criteria

  • Active infectious disease considered by the investigator to be incompatible with the protocol.
  • Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol.
  • History of thrombosis (except tumor invading great vessel) within 1 year of study or if concurrent anticoagulation required, except low-dose warfarin (up to 1 mg/day).
  • Patients not recovered from any therapy-related toxicities from previous chemo-, hormone-, immuno-, molecular targeted, or radiotherapies to at least CTCAE = Grade 1. Prior chemotherapy is allowed if completed at least 4 weeks prior to first trial treatment (6 weeks for mitomycin C or nitrosoureas) and the patient has recovered from the acute toxicities of that therapy.
  • Patients with untreated or symptomatic brain metastases. Patients with treated, asymptomatic brain metastases are eligible if there has been no change in brain disease status for at least 4 weeks before starting trial medication, no history of cerebral oedema or bleeding in the past 4 weeks before starting trial medication and must be on a stable or reducing dose of dexamethasone. Anti-epileptic therapy will be allowed if the patient is stable on antiepileptic treatment for 4 weeks, or more, without adjustments before starting trial medication.
  • Patients who have been treated with any of the following within 4 weeks of starting trial medication: chemotherapy, immunotherapy, radiotherapy, molecular-targeted therapy, biological therapies (including trastuzumab), hormone therapy for breast cancer within 2 weeks of starting trial medication (excluding LHRH agonists in prostate cancer, or bisphosphonates), or treatment with other investigational drugs.
  • Use of any investigational drug within 4 weeks before start of trial medication or concomitantly with this trial.
  • Patients unable to comply with the protocol.
  • Active alcohol abuse or active drug abuse (at the discretion of the investigator).
  • Patients with unstable arrhythmias or unstable angina or severe obstructive pulmonary disease within the last year.
  • For patients entering Part II of the study, prior use of any IGF inhibitor.
  • Pregnancy or breast feeding.
  • Other malignancy requiring active therapy.
  • Patients with a history of diabetes mellitus.
  • For patients that are to undergo tumor biopsy, a history of a hereditary bleeding disorder or clinically relevant major bleeding event in the past 6 months as judged by the investigator (this criterion is limited to patients in Part II only)

Treatment and study plan

BI 836845

Drug

Intravenous infusion once every week

Other names: Xentuzumab

Primary outcomes

  1. Part 1: Maximum Tolerated Dose (MTD) of BI 836845 During the First Treatment Course of the Dose Escalation Phase.

    Time frame: During the first course of treatment, up to 21 days

    In the absence of MTD, the relevant biological dose (RBD) of BI 836845 during the first treatment course of the dose escalation phase was reported. The MTD was defined as the highest dose level of BI 836845 at which no more than 1 out of 6 patients experienced a drug related dose limiting toxicity (DLT) during the first course of treatment. Starting dose of 10 milligrams (mg) BI 836845, administered thrice every 3 weeks. Dose levels evaluated were: 10 mg, 20 mg, 40 mg, 60 mg, 90 mg, 135 mg, 200 mg, 300 mg, 450 mg, 600 mg, 800 mg, 1050 mg, 1400 mg and 1800 mg.

    The BI 836845 dose which could achieve a plateau in total Insulin-like growth factor 1 (IGF-1) plasma concentrations was considered the RBD.

  2. Part 1: Number of Patients With Dose Limiting Toxicities (DLTs) During the Maximum Tolerated Dose (MTD) Evaluation Period

    Time frame: During the first course of treatment, up to 21 days

    Number of participants with DLTs occurring during the first treatment course of the dose escalation part. DLT was defined as drug-related adverse events meeting the criteria summarized below:

    • Common terminology criteria for adverse events (CTCAE) grade 4 neutropenia for ≥ 7 days (d)
    • Febrile neutropenia with single temperature of > 38.3°C/ ≥ 38°C more than 1 hour (h)
    • Documented infection with high neutrophile count
    • CTCAE grade 4 thrombocytopenia/CTCAE grade 3 thrombocytopenia associated with bleeding requiring transfusion
    • AST (Aspartate Amino Transferase)/ALT (Alanine Amino Transferase) > 5x normal
    • CTCAE grade 3/4 non-hematologic toxicity
    • CTCAE grade ≥2 infusion reaction
    • CTCAE grade ≥2 nausea and/or vomiting for ≥7 d
    • CTCAE grade ≥3 skin toxicity
    • CTCAE grade ≥3 hyperglycemia
    • Any electrolyte grade 3 AE
    • No recovery from non-DLT CTCAE grade >2
    • Sustained fatigue/asthenia grade 3 for longer than 96 h
    • Other event qualified as DLT by the investigator

Secondary outcomes

  1. Objective Tumour Response Based on Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1

    Time frame: First treatment administration until the earliest of disease progression, death, last adequate tumor assessment or the start of subsequent anti-cancer therapy. Up to 72 weeks.

    Number of patients with the objective response (OR). Objective response was defined as best overall response of complete response (CR) or partial response (PR) (with no confirmation required) based on Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. CR was defined by the disappearance of all target lesions and PR was defined by a decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference. The best overall response was recorded since first administration of the trial medication and until the earliest of disease progression, death, last adequate tumor assessment or the start of subsequent anti-cancer therapy.

  2. Duration of Objective Response

    Time frame: First treatment administration until the earliest of disease progression, death, last adequate tumor assessment or the start of subsequent anti-cancer therapy. Up to 72 weeks.

    Duration of objective response (days), defined as time from first objective response to the time to progression or death and was only calculated for patients with an objective response (with no confirmation required).

  3. Best Overall Response Based on Response Evaluation Criteria In Solid Tumours (RECIST) Criteria Version 1.1

    Time frame: First treatment administration until disease progression or last evaluable assessment in absence of progression; Up to 72 weeks

    Number of patients with best overall response. Best overall response represented the best response (complete response - CR, partial response - PR, stable disease -SD, progressive disease - PD) a patient had during their time in the study from first administration of trial medication until the earliest date of progression, or the last evaluable assessment in the absence of progression or the start of subsequent anti-cancer therapy. CR was defined by the disappearance of all target lesions and PR was defined by a decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

  4. Disease Control

    Time frame: First treatment administration until the earliest of disease progression, death, last adequate tumor assessment or the start of subsequent anti-cancer therapy. Up to 72 weeks.

    Number of patients with Disease control. Disease control was defined as best overall response of CR, PR or SD >24 week, with no confirmation required.

  5. Part 2 - Biopsiable Tumours: Progression-free Survival (PFS)

    Time frame: First treatment administration until tumour progression or death. Up to 72 weeks

    PFS was evaluated only for cohort 2 (Biopsiable tumors) in expansion phase of the study. PFS was defined as the time from first treatment administration until tumour progression according to RECIST 1.1 or death from any cause, whichever occurred earlier. Median duration along with 95% confidence interval is based on Kaplan-Meier method.

  6. Maximum Measured Concentration of the BI 836845 in Plasma (Cmax)

    Time frame: Up to 337 hours. Detailed timeframe is in the description.

    Maximum measured concentration of the BI 836845 in plasma (Cmax). Geometric mean (gMean) and Geometric coefficient of variation (gCV) is presented for each course. As defined in the CTP, PK data is presented by BI 836845 dose level and was not collected for Course 4 part 2.

    For Course 1 of part 1 and part 2, Course 2 part 1 and part 2, Course 3 part 2, Course 4 part 1 the following timeframe applies : At 0.083 hour before and 0.5, 1, 2, 4, 7, 24, 72*, 168, 169, 336 and 337 hours after infusion. * applies only to part 1 administration courses. In Course 3 of part 1 the following timeframe applies: At 0.083 hour before and 0.5, 1, 168, 169, 336 and 337 hours after infusion.

  7. Time to Maximum Measured Concentration BI 836845 in Plasma (Tmax)

    Time frame: Up to 337 hours. Detailed timeframe is in the description.

    Time to maximum measured concentration of the BI 836845 in plasma (tmax). As defined in the CTP, PK data is presented by BI 836845 dose level and was not collected for Course 4 part 2.

    For Course 1 of part 1 and part 2, Course 2 part 1 and part 2, Course 3 part 2, Course 4 part 1 the following timeframe applies : At 0.083 hour before and 0.5, 1, 2, 4, 7, 24, 72*, 168, 169, 336 and 337 hours after infusion. * applies only to part 1 administration courses. In Course 3 of part 1 the following timeframe applies: At 0.083 hour before and 0.5, 1, 168, 169, 336 and 337 hours after infusion.

  8. Area Under the Plasma Concentration-time Curve of BI 836845 From Time 0 to 168 Hours (AUC 0-168)

    Time frame: Up to 337 hours. Detailed timeframe is in the description.

    Area under the plasma concentration-time curve from time 0 to 168 hours (AUC 0-168) of the BI 836845. As defined in the CTP, PK data is presented by BI 836845 dose level and was not collected for Course 4 part 2.

    For Course 1 of part 1 and part 2, Course 2 part 1 and part 2, Course 3 part 2, Course 4 part 1 the following timeframe applies : At 0.083 hour before and 0.5, 1, 2, 4, 7, 24, 72*, 168, 169, 336 and 337 hours after infusion. * applies only to part 1 administration courses. In Course 3 of part 1 the following timeframe applies: At 0.083 hour before and 0.5, 1, 168, 169, 336 and 337 hours after infusion.

    In the arm BI 836845 450 mg, data from 3 participants was available (15800, 20400 and 12700); as these 3 subjects represented less than 2/3 of the participants included in this course and this dose group, no descriptive statistics were presented in the Clinical Trial Report. The gMean and gCV values were calculated post hoc for ClinicalTrials.gov disclosure purpose only.

  9. Incidence and Intensity of Adverse Events (AEs) According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)

    Time frame: First treatment administration until end of treatment plus residual effect period; Up to 74 weeks

    Number of patients with adverse events (AEs) according to the grading as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. The intensity of AEs was defined based on:

    • Grade 1 - Mild AE; awareness of sign(s) or symptom(s) which is/are easily tolerated.
    • Grade 2 - Moderate AE; enough discomfort to cause interference with usual activity.
    • Grade 3 - Severe AE; incapacitating or causing inability to work or to perform usual activities.
    • Grade 4 - Life-threatening or disabling AE.
    • Grade 5 - Death related to AE.

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study title

A Phase I Dose Escalation Trial of Weekly Intravenous Administrations of BI 836845 in Patients With Advanced Solid Cancers With Repeated Administrations in Patients Showing Clinical Benefit

Important dates

Study start
2011
Primary completion
2015
Study completion
2015
First posted
Jul 27, 2011
Registry last updated
Jul 25, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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