Trial to Determine MTD of BI 836845 Administered Intravenously Once Every Three Weeks in Patients With Advanced Solid Tumours and Later a Weekly Dosing Schedule in Selected Tumour Types

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Boehringer Ingelheim
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01317420
First received: March 15, 2011
Last updated: August 6, 2014
Last verified: August 2014
  Purpose

This study is a phase I, open-label, dose escalation trial to determine the maximum tolerated dose (MTD) of a new drug BI 836845 which blocks the insulin 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).


Condition Intervention Phase
Neoplasms
Drug: BI 836845
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Dose Escalation Trial of BI 836845 Administered Intravenously Once Every Three Weeks in Patients With Advanced Solid Tumours During Escalation and Weekly in Selected Tumour Types During Expansion, With Repeated Administrations in Patients Showing Clinical Benefit.

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Occurence of drug related dose limiting toxicities for determination of Maximum Tolerated Dose (MTD) (Part I) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Occurence of drug related dose limiting toxicities (DLT) (Part I) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Part I) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Response rate (CR/PR/SD) according to RECIST criteria 1.1 (Part II). [ Time Frame: up to 44 months ] [ Designated as safety issue: No ]
  • Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Part II) [ Time Frame: up to 44 months ] [ Designated as safety issue: No ]
  • Intensity of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Part I) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Duration of objective response (CR/PR), defined as time from first objective response to the time to progression or death (Part II). [ Time Frame: up to 44 months ] [ Designated as safety issue: No ]
  • Intensity of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Part II) [ Time Frame: up to 44 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Maximum measured plasma concentration (Cmax). (Part I and II) [ Time Frame: up to 336 ] [ Designated as safety issue: No ]
  • Time from dosing to the maximum plasma concentration (tmax). (Part I and II) [ Time Frame: up to 336 hours ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve over the time interval of one week (AUC0-168). (Part I and II) [ Time Frame: up to 168 hours ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve over one dosing interval (AUC0-t). (Part I and II) [ Time Frame: up to 168 hours ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve over the time interval from zero extrapolated to infinity (AUC0-inf). (Part I and II) [ Time Frame: up to 336 hours ] [ Designated as safety issue: No ]
  • Terminal half-life (t1/2). (Part I and II) [ Time Frame: up to 336 hours ] [ Designated as safety issue: No ]
  • Mean residence time after intravenous infusion (MRT). (Part I and II) [ Time Frame: up to 336 hours ] [ Designated as safety issue: No ]
  • Total plasma clearance (CL). (Part I and II) [ Time Frame: up to 336 hours ] [ Designated as safety issue: No ]
  • Apparent volume of distribution during the terminal phase (Vz). (Part I and II) [ Time Frame: up to 336 hours ] [ Designated as safety issue: No ]
  • Volume of distribution after intravenous infusion at steady state (Vss). (Part II) [ Time Frame: up to 336 hours ] [ Designated as safety issue: No ]

Estimated Enrollment: 72
Study Start Date: April 2011
Estimated Study Completion Date: December 2015
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Monotherapy
BI 836845 dose escalation, infusion, once every three weeks, monotherapy
Drug: BI 836845
Intravenous infusion once every three weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Male or female patients with cytologically or histologically confirmed solid tumours that are refractory to standard therapy or that have no standard therapy.
  2. Patients should have evaluable disease, or at least one measurable lesion according to Response Evaluation Criteria In Solid Tumours (RECIST) criteria version 1.1
  3. Age, equal, or more than, 18 years old.
  4. Life expectancy of at least 3 months.
  5. Written informed consent that is consistent with ICH-GCP guidelines.
  6. Eastern Cooperative Oncology Group (ECOG) performance score 0, 1 or 2.
  7. Patients must have recovered from any previous surgery and no major surgery within the last 28 days prior to start of trial medication.
  8. Cardiac left ventricular function with resting ejection fraction >50% as determined by Echocardiography (ECHO) or Multiple Gated Acquisition scan (MUGA).
  9. Absolute neutrophil count equal, or more than, 1,500/µl.
  10. Platelets equal, or more than, 100,000/µl.
  11. Total bilirubin equal, or less than 1.5 x institution upper limit of normal.
  12. Aspartate Amino Transferas (AST) (Serum glutamic oxaloacetic transaminase (SGOT)) / Alanine Amino Transferase (ALT) (Serum glutamic pyruvic transaminase (SGPT )) equal, or less than, 2.5 x upper limit of normal (in case of known liver metastases AST and/or ALT, equal, or less than, 5 x upper limit of normal).
  13. Creatinine equal, or less than, 1.5 x institution upper limit of normal.
  14. Haemoglobin equal, or more than, 9g/dL.
  15. Haemoglobin A1c less than 8% and fasting glucose, equal, or less than, 8.9 mmol/L (= 160 mg/dL).
  16. 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.
  17. Patients enetering part II of the study should have cytologically or histologically confirmed disease from the Ewing's family of tumours/PNET (cohort 1), or solid tumours suitable for biopsy (cohort 2), that are refractory to standard therapy or that have no standard therapy.
  18. Patients eligible to undergo biospy should have normal coagulation parameters (INR and PTT within normal ranges) and platelet count (equal, or more than, 100,000/µl) prior to biospy tissue collection.

Exclusion criteria:

  1. Active infectious disease.
  2. Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol.
  3. History of thrombosis within 1 year of study or if concurrent anticoagulation required, except low-dose warfarin (up to 1mg/day).
  4. Patients not recovered from any therapy-related toxicities from previous chemo-, hormone-, immuno-, molecular targeted, or radiotherapies to at least Common Terminology Criteria for Adverse Events (CTCAE) equal, or less than, 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.
  5. 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.
  6. Patients who have been treated with any of the following within 4 weeks of starting trial medication: chemotherapy, immunotherapy, radiotherapy, biological therapies (including trastuzumab), molecular targeted, hormone therapy for breast cancer within 2 weeks of starting trial medication (excluding Luteinizing-hormone-releasing hormone (LHRH) agonists in prostate cancer, or bisphosphonates), or treatment with other investigational drugs.
  7. Participation in another clinical trial within the past 4 weeks before start of therapy or concomitantly with this trial.
  8. Patients unable to comply with the protocol.
  9. Active alcohol abuse or active drug abuse (at the discretion of the investigator).
  10. Patients with unstable arrhythmias or unstable angina or severe obstructive pulmonary disease within the last year.
  11. For patients entering part II of the study, prior use of any insulin growth factor (IGF) inhibitor.
  12. Patients with a history of diabetes mellitus.
  13. Pregnancy or breast feeding.
  14. Patients that are to undergo biospy should not have a history of a hereditary bleeding disorder as judged by the investigator.
  15. Patients that are to undergo biospy should pause acetylsalicylic acid treatment for at least 7 days prior to biospy tissue collection.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01317420

Contacts
Contact: Boehringer Ingelheim Call Center 1-800-243-0127 clintriage.rdg@boehringer-ingelheim.com

Locations
United Kingdom
1280.2.4402 Boehringer Ingelheim Investigational Site Recruiting
Leeds, United Kingdom
1280.2.4401 Boehringer Ingelheim Investigational Site Recruiting
Sutton, United Kingdom
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01317420     History of Changes
Other Study ID Numbers: 1280.2, 2010-021714-29
Study First Received: March 15, 2011
Last Updated: August 6, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on August 25, 2014