Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

BIBW 2992 (Afatinib) in Combination With Pemetrexed in Advanced Solid Tumours

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01169675
First received: July 19, 2010
Last updated: June 3, 2014
Last verified: January 2014
  Purpose

This Phase I study will investigate the safety of BIBW 2992 in combination with standard dose pemetrexed (500mg/m2) given on a 21 day cycle in patients with advanced solid cancers. BIBW 2992 will be given on two different dose schedules; dosing on days 1-21 and dosing on days 1 to 6 of a 21 day cycle.

The use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), including BIBW 2992 have demonstrated efficacy in solid tumors including non-small cell lung cancer (NSCLC). In addition, pemetrexed has demonstrated efficacy and has been approved as single agent chemotherapy in second-line NSCLC patients with adenocarcinoma. The data obtained from this trial shall allow for a conclusion as to whether BIBW 2992 may be safely administered in advanced cancer patients in combination therapy with pemetrexed.


Condition Intervention Phase
Neoplasms
Drug: BIBW 2992 low dose
Drug: BIBW 2992 high dose
Drug: pemetrexed
Drug: BIBW 2992 high dose 6 day
Drug: BIBW 2992 low dose 6 day
Drug: BIBW 2992 medium dose 6 day
Drug: BIBW 2992 medium dose
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: BIBW 2992 Phase I Combination With Pemetrexed in Advanced Solid Tumours

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Investigator Defined Dose Limiting Toxicity (DLT) During First Course of Treatment, Treated Set [ Time Frame: DLT were assessed during the first cycle (days 1-21) ] [ Designated as safety issue: No ]
    Occurence of DLT during the first course of treatment to determine the maximum tolerated dose (MTD) of Afatinib at two different dose schedules in combination with the standard established dose of pemetrexed (500 mg/m2).


Secondary Outcome Measures:
  • Investigator Defined Dose Limiting Toxicity (DLT) During All Courses of Treatment, Treated Set [ Time Frame: DLT were assessed during all cycles of treatment ] [ Designated as safety issue: No ]
    Occurence of DLT during all courses of treatment with Afatinib at two different dose schedules in combination with the standard established dose of pemetrexed (500 mg/m2).

  • Objective Response (OR) [ Time Frame: Every 6 weeks before week 48 and every 12 weeks after week 48 until progression ] [ Designated as safety issue: No ]

    Objective Response is defined as complete response or partial response according to the response evaluation criteria in solid tumours (RECIST) version 1.1.

    Complete Response (CR): disappearance of all non-target lesions and normalization of tumor marker level; Partial Response (PR): at least 30% decrease of the sum of longest diameter (LD) of target lesions; Progressive Disease (PD): at least a 20% increase in the sum of LD of target lesions together with an absolute increase in the sum of LD of at least 5 millimeters; Stable Disease (SD): neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for PD.


  • Disease Control [ Time Frame: Every 6 weeks before week 48 and every 12 weeks after week 48 until progression ] [ Designated as safety issue: No ]
    Disease Control is defined as complete response, partial response, or stable disease according to the response evaluation criteria in solid tumours (RECIST) version 1.1.

  • Progression Free Survival (PFS) [ Time Frame: Every 6 weeks before week 48 and every 12 weeks after week 48 until progression ] [ Designated as safety issue: No ]
    PFS was defined as the time from the first treatment to the occurence of tumour progression or death, whichever came first. It was assessed according to RECIST version 1.1 criteria.

  • Tumour Shrinkage [ Time Frame: Every 6 weeks before week 48 and every 12 weeks after week 48 until progression ] [ Designated as safety issue: No ]
    Tumour shrinkage is defined as the maximum percentage decrease from baseline in the sum of the longest diameters of target lesions.


Enrollment: 53
Study Start Date: July 2010
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIBW 2992 low dose
patient receives low dose tablet BIBW 2992 po daily plus pemetrexed 500mg/m^2 on day 1 of 21 day cycle
Drug: BIBW 2992 low dose
patient receives low dose BIBW 2992 po daily on day 1 of 21 day cycle
Drug: pemetrexed
given intravenously on day 1 of a 21 day cycle
Experimental: BIBW 2992 medium dose
patient receives medium dose BIBW 2992 po daily plus pemetrexed 500mg/m^2 on day 1 of 21 day cycle
Drug: pemetrexed
given intravenously on day 1 of a 21 day cycle
Drug: BIBW 2992 medium dose
patient receives medium dose BIBW 2992 po daily on day 1 of 21 day cycle
Experimental: BIBW 2992 high dose
patient receives high dose BIBW 2992 po daily plus pemetrexed 500mg/m^2 on day 1 of 21 day cycle
Drug: BIBW 2992 high dose
patient receives high dose BIBW 2992 po daily on day 1 of 21 day cycle
Drug: pemetrexed
given intravenously on day 1 of a 21 day cycle
Experimental: BIBW 2992 low dose 6 day
patient receives low dose BIBW 2992 po daily on days 1-6 plus pemetrexed 500mg/m^2 on day 1 of 21 day cycle
Drug: pemetrexed
given intravenously on day 1 of a 21 day cycle
Drug: BIBW 2992 low dose 6 day
patient receives low dose BIBW 2992 po daily on days 1-6 on day 1 of 21 day cycle
Experimental: BIBW 2992 medium dose 6 day
patient receives medium BIBW 2992 po daily on days 1-6 plus pemetrexed 500mg/m^2 on day 1 of 21 day cycle
Drug: pemetrexed
given intravenously on day 1 of a 21 day cycle
Drug: BIBW 2992 medium dose 6 day
patient receives medium dose BIBW 2992 po daily on day1 to 6 of a 21 day cycle
Experimental: BIBW 2992 high dose 6 day
patient receives high dose BIBW 2992 po daily on days 1-6 plus pemetrexed 500mg/m^2 on day 1 of 21 day cycle
Drug: BIBW 2992 high dose 6 day
patient receives high dose BIBW 2992 po daily on days 1-6 on 1 of 21 day cycle
Drug: pemetrexed
given intravenously on day 1 of a 21 day cycle

  Eligibility

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

Inclusion criteria:

  1. Age 18 or older.
  2. Eastern cooperative oncology group performance status of 0-2.
  3. Life expectancy of at least 12 weeks.
  4. Measurable disease according to Response evaluation criteria in solid tumors 1.1 criteria.
  5. Written informed consent

Exclusion criteria:

  1. Treatment with an investigational drug within the past 28 days prior to the start of therapy
  2. Persisting toxicities which are clinically significant from previous therapy
  3. Patients who are unwilling or unable to take folic acid and vitamin B12 supplementation
  4. Active brain metastases
  5. Other active malignancy diagnosed within the past 3 years
  6. Concomitant intercurrent illnesses that would limit compliance with trial requirement
  7. Patients unable or unwilling to interrupt concomitant administration of Non-steroidal anti-inflammatory drugs (NSAIDS) as per pemetrexed prescribing information
  8. Patients who have received prior therapy with BIBW 2992
  9. Left ventricular function by echocardiogram or Multiple gated acquisition scan (MUGA) less than institutional lower limit of normal
  10. Absolute neutrophil count (ANC) less than 1,500/mm3
  11. Platelet count less than 100,000/mm3
  12. Hemoglobin less than 90g/L
  13. Total bilirubin less than 26µmol/L
  14. Alanine amino transferase (ALT) and/or aspartate amino transferase (AST) greater than 2.5 X ULN, except in case of known liver metastasis where maximum 5 X ULN is acceptable
  15. Serum creatinine level greater than 133µmol/L and/or creatinine clearance (measured or calculated) less than 45 ml/min
  16. History or recent gastrointestinal bleeding, obstruction or perforation or malabsorption syndrome and must be able to swallow the BIBW 2992 in whole by mouth.
  17. History of interstitial lung disease
  18. Women and men who are sexually active and unwilling to use a medically acceptable method of contraception
  19. Pregnancy or breast feeding
  20. Known or suspected active alcohol or drug abuse
  21. Patients unable to comply with the protocol
  22. Has a diagnosis of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
  23. Any known hypersensitivity to the trial drugs or their excipients
  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: NCT01169675

Locations
Canada, Alberta
1200.92.1001 Boehringer Ingelheim Investigational Site
Edmonton, Alberta, Canada
Canada, Ontario
1200.92.1002 Boehringer Ingelheim Investigational Site
Hamilton, Ontario, Canada
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01169675     History of Changes
Other Study ID Numbers: 1200.92
Study First Received: July 19, 2010
Results First Received: October 30, 2013
Last Updated: June 3, 2014
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Pemetrexed
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014