Skip to main content
OpenTrials
Completed

NCT Number: NCT00993499

Trial of Continuous Once Daily Oral Treatment Using BIBW 2992 (Afatinib) Plus Sirolimus (Rapamune®) in Patients With Non-small Cell Lung Cancer Harbouring an EGFR Mutation and/or Disease Progression Following Prior Erlotinib or Gefitinib

The primary objective of this trial is to identify the Maximum Tolerated Dose of BIBW 2992 therapy when given continuously in combination with Sirolimus.

The MTD will be based on the Dose Limiting Toxicity information collected during the first two cycles.

Overall safety, pharmacokinetics and anti-tumour efficacy will be evaluated as secondary objectives.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Carcinoma, Non-Small-Cell Lung Bronchial Neoplasms Carcinoma, Bronchogenic Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

1200.70.34001 Boehringer Ingelheim Investigational Site, Badalona (Barcelona), Spain

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Pathologically or cytologically confirmed diagnosis of Stage IIIB or Stage IV NSCLC
  • Patients who have failed conventional treatment (at least 1 prior treatment line), or for whom no therapy of proven efficacy exists
  • Patients whose tumors:
  • are EGFR mutation-positive or
  • are EGFR mutation-negative or unknown provided they had disease progression after achieving either response or stable disease for at least 6 months from a previous treatment with erlotinib (Tarceva®) or gefitinib (Iressa®)
  • Patients aged 18 years or older
  • Life expectancy of at least three (3) months
  • Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score 0-2
  • Written informed consent that is consistent with ICH-GCP guidelines

Exclusion criteria

  • Prior major surgery, chemotherapy or radiation therapy within 4 weeks before start of therapy.
  • Prior treatment with an mTOR inhibitor within the past 4 weeks before start of therapy or concomitantly with this study
  • Use of erlotinib (Tarceva®) or gefitinib (Iressa®) within 14 days of run-in treatment with Sirolimus
  • Active CNS metastases (defined as stable for <4 weeks and/or symptomatic and/or requiring treatment with anticonvulsants or steroids)
  • Severe alteration in serum fasting cholesterol (equal or more than 350 mg/dL) or triglycerides (equal or more than 400 mg/dL). Patients may be allowed to enrol on the trial after initiation of lipid lowering agents.
  • Requirement for treatment with any of the prohibited concomitant medications:
  • Concomitant CYP3A4 inhibitors within the past 7 days before start of therapy or concomitantly with this study.
  • Concomitant CYP3A4 inducers within the past 14 days before start of therapy or concomitantly with this study.
  • Any contraindications for therapy with Sirolimus.
  • Known hypersensitivity to BIBW 2992, Sirolimus or other rapamycin analogues (everolimus, temsirolimus, deforolimus, etc.) or the excipients of any of the trial drugs.
  • Use of any investigational drug within 4 weeks before start of therapy.

Treatment and study plan

BIBW 2992

Drug

Dose escalation (19-40 patients): low or high dose oral + 12 addit. pat. at MTD, until progression or undue AEs

Sirolimus (rapamycin)

Drug

Dose escalation (19-40 patients): several dose levels + 12 addit. pat. at MTD until progression or undue AEs.

Primary outcomes

  1. Occurrence of Dose Limiting Toxicities (DLT)

    Time frame: 2 first cycles, 56 days

    Number of participants with of dose limiting toxicities (DLT)

Secondary outcomes

  1. Best Overall Response

    Time frame: From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days

    Best overall response (unconfirmed) according to RECIST v1.1

  2. Objective Response

    Time frame: From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days

    Rate of (unconfirmed) objective response, defined as complete response (CR) or partial response (PR) according to RECIST v1.1

  3. Rate of Disease Control

    Time frame: From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days

    Rate of (unconfirmed) disease control defined as CR, PR, or stable disease (SD), according to RECIST v1.1

  4. Exploratory Examination of EGFR Mutations (Exons 19, 20 and 21 and Others) in Serum/Plasma DNA and Tumour DNA.

    Time frame: Multiple time points during the trial

    Exploratory examination of Epidermal growth factor (receptor)(EGFR) mutations (Exons 19, 20 and 21 and others) in serum/plasma DNA and tumour DNA.

    This endpoint was not analysed in the study report as the available data was too limited.

  5. Maximum Measured Plasma Concentration of Afatinib at Steady State (Cmax,ss)

    Time frame: 24 hours (h), 311h 55minutes (min), 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h and 336h after first administration of afatinib

    Maximum measured plasma concentration of Afatinib at steady state (Cmax,ss)

  6. AUC of Afatinib at Steady State Over the Dosing Interval τ (AUCτ,ss)

    Time frame: 24 hours (h), 311h 55minutes (min), 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h and 336h after first administration of afatinib

    Area under the curve (AUC) of Afatinib at steady state over the dosing interval τ (AUCτ,ss) for afatinib.

  7. Maximum Measured Plasma Concentration of Sirolimus at Steady State (Cmax,ss)

    Time frame: 24 hours (h) 5 minutes (min), 24h, 23h, 22h, 20h, 18h, 16h, 5min before first afatinib administration and 144h, 311h 55min, 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h, 336h, 480h after first administration of afatinib

    Maximum measured plasma concentration of sirolimus at steady state (Cmax,ss)

  8. AUC of Sirolimus at Steady State Over the Dosing Interval τ (AUCτ,ss)

    Time frame: 24 hours (h) 5 minutes (min), 24h, 23h, 22h, 20h, 18h, 16h, 5min before first afatinib administration and 144h, 311h 55min, 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h, 336h, 480h after first administration of afatinib

    Area under the curve (AUC) of sirolimus at steady state over the dosing interval τ (AUCτ,ss) for afatinib.

  9. Occurrence of Adverse Events According to CTCAE, Version 3.0

    Time frame: From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days

    Percentage of participants with adverse events according to highest Common Terminology Criteria for Adverse Events (CTCAE) grade, version 3.0

  10. Percentage of Patients With Drug-related AEs

    Time frame: From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days

    Percentage of patients with drug-related adverse events (AEs).

  11. Frequency of Patients With Possible Clinically-significant Abnormalities in Liver Enzymes or Total Bilirubin

    Time frame: From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days

    Evaluation of laboratory parameters included assessment of the frequency of patients with ALT and AST elevations concurrent with elevated bilirubin and indicative of Hy's law cases.

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study title

A Phase Ib Open Label Clinical Trial of Continuous Once Daily Oral Treatment Using BIBW 2992 Plus Sirolimus in Patients With Non-small Cell Lung Cancer Harbouring an EGFR Mutation and/or Disease Progression Following Prior Erlotinib or Gefitinib

Important dates

Study start
2009
Primary completion
2014
Study completion
2014
First posted
Oct 12, 2009
Registry last updated
Oct 7, 2015

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.

Related clinical trials

Published trials that share one or more normalized conditions with this study.