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NeoplasmsPhase 1NCT01169675

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

A Phase 1 study testing BIBW 2992 low dose, BIBW 2992 high dose and pemetrexed in people with Neoplasms, run by Boehringer Ingelheim at 2 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoplasms
What is being tested?
BIBW 2992 low dose, BIBW 2992 high dose and pemetrexed
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
2 sitesCanada
Study dates
Jul 2010to Nov 2012
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

2 sites in 1 country.

Canada2 sites

  • 1200.92.1001 Boehringer Ingelheim Investigational Site

    Edmonton, Alberta

  • 1200.92.1002 Boehringer Ingelheim Investigational Site

    Hamilton, Ontario

Other trials in Canada

About this study

Official title: BIBW 2992 Phase I Combination With Pemetrexed in Advanced Solid Tumours

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.

Conditions
Neoplasms
Being tested
BIBW 2992 low dose, BIBW 2992 high dose, pemetrexed, BIBW 2992 high dose 6 day, BIBW 2992 low dose 6 day
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BIBW 2992 low doseDrug

    patient receives low dose BIBW 2992 po daily on day 1 of 21 day cycle

  • BIBW 2992 high doseDrug

    patient receives high dose BIBW 2992 po daily on day 1 of 21 day cycle

  • pemetrexedDrug

    given intravenously on day 1 of a 21 day cycle

  • pemetrexedDrug

    given intravenously on day 1 of a 21 day cycle

  • BIBW 2992 high dose 6 dayDrug

    patient receives high dose BIBW 2992 po daily on days 1-6 on 1 of 21 day cycle

  • pemetrexedDrug

    given intravenously on day 1 of a 21 day cycle

  • pemetrexedDrug

    given intravenously on day 1 of a 21 day cycle

  • pemetrexedDrug

    given intravenously on day 1 of a 21 day cycle

  • pemetrexedDrug

    given intravenously on day 1 of a 21 day cycle

  • BIBW 2992 low dose 6 dayDrug

    patient receives low dose BIBW 2992 po daily on days 1-6 on day 1 of 21 day cycle

  • BIBW 2992 medium dose 6 dayDrug

    patient receives medium dose BIBW 2992 po daily on day1 to 6 of a 21 day cycle

  • BIBW 2992 medium doseDrug

    patient receives medium dose BIBW 2992 po daily on day 1 of 21 day cycle

Study groups in NCT01169675
Study groupRoleWhat they receive
BIBW 2992 low doseExperimentalpatient receives low dose tablet BIBW 2992 po daily plus pemetrexed 500mg/m^2 on day 1 of 21 day cycle
Receives: Drug: BIBW 2992 low dose; Drug: pemetrexed
BIBW 2992 medium doseExperimentalpatient receives medium dose BIBW 2992 po daily plus pemetrexed 500mg/m^2 on day 1 of 21 day cycle
Receives: Drug: pemetrexed; Drug: BIBW 2992 medium dose
BIBW 2992 high doseExperimentalpatient receives high dose BIBW 2992 po daily plus pemetrexed 500mg/m^2 on day 1 of 21 day cycle
Receives: Drug: BIBW 2992 high dose; Drug: pemetrexed
BIBW 2992 low dose 6 dayExperimentalpatient receives low dose BIBW 2992 po daily on days 1-6 plus pemetrexed 500mg/m^2 on day 1 of 21 day cycle
Receives: Drug: pemetrexed; Drug: BIBW 2992 low dose 6 day
BIBW 2992 medium dose 6 dayExperimentalpatient receives medium BIBW 2992 po daily on days 1-6 plus pemetrexed 500mg/m^2 on day 1 of 21 day cycle
Receives: Drug: pemetrexed; Drug: BIBW 2992 medium dose 6 day
BIBW 2992 high dose 6 dayExperimentalpatient receives high dose BIBW 2992 po daily on days 1-6 plus pemetrexed 500mg/m^2 on day 1 of 21 day cycle
Receives: Drug: BIBW 2992 high dose 6 day; Drug: pemetrexed

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Investigator Defined Dose Limiting Toxicity (DLT) During First Course of Treatment, Treated Set

    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).

    Measured: DLT were assessed during the first cycle (days 1-21)

Secondary outcomes (5)

  1. Investigator Defined Dose Limiting Toxicity (DLT) During All Courses of Treatment, Treated Set

    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).

    Measured: DLT were assessed during all cycles of treatment

  2. Objective Response (OR)

    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.

    Measured: Every 6 weeks before week 48 and every 12 weeks after week 48 until progression

  3. Disease Control

    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.

    Measured: Every 6 weeks before week 48 and every 12 weeks after week 48 until progression

  4. Progression Free Survival (PFS)

    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.

    Measured: Every 6 weeks before week 48 and every 12 weeks after week 48 until progression

  5. Tumour Shrinkage

    Tumour shrinkage is defined as the maximum percentage decrease from baseline in the sum of the longest diameters of target lesions.

    Measured: Every 6 weeks before week 48 and every 12 weeks after week 48 until progression

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jul 2010 (estimated)
  2. Study startJul 2010
  3. Primary completionNov 2012
  4. Study completionNov 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01169675
Sponsor's protocol ID
1200.92
Status last verified
Jan 2014
First submitted
19 Jul 2010
Last updated
9 Jun 2014

Publications

  • Chu QS, Sangha R, Hotte SJ, Sergenson G, Schnell D, Chand VK, Hirte HW. A phase I, dose-escalation trial of continuous- and pulsed-dose afatinib combined with pemetrexed in patients with advanced solid tumors. Invest New Drugs. 2014 Dec;32(6):1226-35. doi: 10.1007/s10637-014-0139-9. Epub 2014 Jul 19.

    PubMed 25037863

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BIBW 2992 low dose, BIBW 2992 high dose and pemetrexed in people with Neoplasms, run by Boehringer Ingelheim at 2 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Dec 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01169675, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2014.

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