HER-2 Positive Gastric CancerPhase 2NCT02274012
Trial of Afatinib in Combination With Weekly Paclitaxel in the Second Line Treatment
A Phase 2 study testing Afatinib and Paclitaxel in people with HER-2 Positive Gastric Cancer and Gastrooesophageal Cancer, run by Columbia University.
Trial summary
The investigators are doing this research program to find out if the investigational drug, afatinib which is a medication known to block the function of the ErbB2 protein might help standard chemotherapy, in particular paclitaxel, work better. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER-2 Positive Gastric Cancer, Gastrooesophageal Cancer, Esophageal Cancer
- What is being tested?
- Afatinib and Paclitaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 29 May 2014to 12 Aug 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the intrathoracic esophagus, gastrointestinal junction or stomach.
- Tumor must be HER2 positive 3+ by immunohistochemistry or positive by Fluorescence in situ hybridization (FISH) analysis if 2+ by immunohistochemistry.
- Received and failed at least one prior cytotoxic chemotherapy regimen for advanced disease that included trastuzumab.
- Age greater than or equal to 18 years.
- At least one measurable lesion as defined by modified RECIST criteria.
- ECOG performance status less than or equal to 2.
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- Life expectancy of at least 12 weeks.
- Normal organ and marrow function as defined.
- Able to swallow and retain oral medication.
- Left ventricular ejection fraction (LVEF) within institutional range of normal as measured by echocardiogram (ECHO).
- Prior malignancy is acceptable if the subject is considered to be cured.
- Ability to understand and the willingness to sign a written informed consent document.
- All subjects of childbearing potential must agree to use acceptable methods of birth control (Men and Women).
- Willingness to consent to the use of baseline diagnostic tumor specimen for correlative studies.
Who cannot join
- Squamous cell carcinoma.
- History of clinically relevant cardiovascular abnormalities within 6 months.
- Baseline (less than 1 month before treatment) cardiac left ventricular function with resting ejection fraction of less than 50 percent measured by multigated blood pool imaging of the heart (MUGA scan) or echocardiogram.
- Pregnant and lactating women are excluded from the study.
- Significant or recent acute gastrointestinal disorders with diarrhea.
- More than 2 prior cytotoxic chemotherapy regimens for relapsed or metastatic disease.
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- Major surgery, chemotherapy, radiation therapy or other cancer therapy within 3 weeks of treatment day 1.
- Use of any investigational drug within 4 weeks.
- Prior treatment with taxanes if given as full-dose chemotherapy for advanced disease.
- Prior treatment with afatinib or any other HER2 inhibitor other than trastuzumab.
- Front-line chemotherapy that did not contain trastuzumab.
- Active central nervous system disease (CNS) metastases.
- Planned concurrent anti-cancer therapy while taking investigational treatment.
- Unresolved or unstable, serious toxicity from prior cancer treatment (any toxicities greater than grade 2).
- Peripheral neuropathy of Grade 2 or greater
- Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety.
- Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to paclitaxel
- Prior anthracycline therapy with a cumulative dose of doxorubicin (or equivalent) greater than or equal to 400 mg/m2
- Pre-existing or current interstitial lung disease
- Known Hypersensitivity to Afatinib (BIBW 2992) or the excipients of any of the trial drugs.
- Patients unable to comply with the protocol.
- Active hepatitis B infection, active hepatitis C infection or known human immunodeficiency virus HIV carrier.
- Known or suspected active drug or alcohol abuse.
- Concomitant treatment with strong inhibitors or inducers of P-glycoprotein.
About this study
Official title: Phase II Trial of Afatinib in Combination With Weekly Paclitaxel in the Second Line Treatment of HER2 Amplified Advanced Gastric, Gastroesophageal Junction and Esophageal Cancer
The investigators are doing this research program to find out if the investigational drug, afatinib which is a medication known to block the function of the ErbB2 protein might help standard chemotherapy, in particular paclitaxel, work better.
Afatinib (GILOTRIF) is a highly potent, irreversible inhibitor of the EGFR and HER2. On July 12, 2013 the United States Food and Drug Administration (US FDA) approved afatinib for the first-line treatment of patients with metastatic non-small cell lung cancer whose tumors had specific EGFR gene mutations (exon 19 deletions or exon 21 i.e. L858R substitution mutations) as detected by an FDA approved test.
Read more
Paclitaxel is a standard, anti-cancer medicine that has been approved by the US Food and Drug Administration (FDA) for the treatment of lung cancer.
The combination of Afatinib and Paclitaxel are considered investigational when used in this research program. An investigational drug is a drug that is not approved by the FDA for its indication.
Read the detailed description
Standard Procedures:
Subjects are offered second line chemotherapy with paclitaxel 80 mg/m2 intravenous infusion over 60 minutes on days 1, 8, and 15 of a 28-day cycle until disease progression or intolerable toxicity.
Experimental Procedures:
In addition to the standard chemotherapy, afatinib 40 mg orally once daily will be administered starting on the first day of paclitaxel. Translational studies to assess circulating tumor cells at the start of therapy and then at several later time points, including at the time of progression. These studies will assess the correlation of circulating tumor cell numbers with radiographic response and pilot studies will also be conducted to assess HER2 expression, HER2 genomic amplification, HER2 pathway activation and secondary genetic changes in the HER2 coding sequence as well as other pathway components.
- Being tested
- Afatinib, Paclitaxel
- Keywords
- Gastric, Gastroesophageal Junction, Gastroesophageal Cancer, Esophageal Cancer, Metastatic, HER2 amplified, Afatinib
- Medical subject headings
- Esophageal Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AfatinibDrug
Also called BIBW 2992
Afatinib 40mg/PO daily will be administered in combination to standard of care paclitaxel.
PaclitaxelDrug
Also called Taxol
On the day of the first dose of afatinib, paclitaxel will be administered at a dose of 80 mg/m2 intravenously over 60 minutes on days 1, 8 and 15 of a 28-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Afatinib and weekly Paclitaxel | Experimental | In addition to the standard chemotherapy, afatinib 40 mg orally once daily will be administered starting on the first day of paclitaxel. Translational studies to assess circulating tumor cells at the start of therapy and then at several later time points, including at the time of progression. These studies will assess the correlation of circulating tumor cell numbers with radiographic response and pilot studies will also be conducted to assess HER2 expression, HER2 genomic amplification, HER2 pathway activation and secondary genetic changes in the HER2 coding sequence as well as other pathway components. Receives: Drug: Afatinib; Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of tumor burden (in centimeters) for participants during protocol therapy
Measured: Change from Baseline Tumor burden, measured every 8 weeks, up to approximately 4 years
Secondary outcomes (5)
Number of participants with adverse events.
Safety of BIBW 2992 will be evaluated as indicated by intensity and incidence of adverse events, graded according to US National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) Version 4.0. Safety endpoints include:
- events leading to dose reduction
- events leading to permanent treatment discontinuation
- the overall incidence and CTC criteria grade of adverse events, as well as relatedness of adverse events to treatment
- causes of death
Measured: up to approximately 36 months
Total number of circulating tumor cell (CTC) numbers.
CTC number changes from cycle 1, day 1 to cycle 2/3, day 1 will be correlated with response rate, progression-free survival as well as skin toxicity.
Measured: up to approximately 36 months
Clinical benefit in progression free survival.
Measured: every 3 months up to approximately 4 years
Clinical benefit in overall survival.
Measured: every 3 months up to approximately 4 years
ErbB2 levels benefit during therapy.
Diagnostic tumor specimens will be retrieved for all subjects participating in the protocol. These specimens will be used for confirmation of ErbB2 status as well as correlative analyses of clinical response.
Measured: up to approximately 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2014 (estimated)
- Study start29 May 2014 (estimated)
- Primary completion12 Aug 2015
- Study completion12 Aug 2015
Why it stopped: Former PI left institution and had plans to continue at another institution.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER-2 Positive Gastric CancerStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- Boehringer Ingelheim
- Responsible party
- Principal investigator, Naiyer Rizvi, Columbia University
- Investigators
- Naiyer Rizvi, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02274012
- Sponsor's protocol ID
- AAAM5905
- Other IDs
- 1200.203
- Status last verified
- Mar 2017
- First submitted
- 15 Oct 2014
- Last updated
- 14 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Afatinib in Combination With Weekly Paclitaxel in the Second Line Treatment of HER2 Amplified Advanced Gastric, Gastroesophageal Junction and Esophageal Cancer
- ClinicalTrials.gov ID
- NCT02274012
- Acronym / sponsor ID
- AAAM5905
- Keywords
- Gastric, Gastroesophageal Junction, Gastroesophageal Cancer, Esophageal Cancer, Metastatic, HER2 amplified, Afatinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Former PI left institution and had plans to continue at another institution.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- Boehringer Ingelheim
- Study start
- 29 May 2014 (estimated)
- Primary completion
- 12 Aug 2015 (actual)
- Study completion
- 12 Aug 2015 (actual)
- First posted
- 24 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators are doing this research program to find out if the investigational drug, afatinib which is a medication known to block the function of the ErbB2 protein might help standard chemotherapy, in particular paclitaxel, work better.
Afatinib (GILOTRIF) is a highly potent, irreversible inhibitor of the EGFR and HER2. On July 12, 2013 the United States Food and Drug Administration (US FDA) approved afatinib for the first-line treatment of patients with metastatic non-small cell lung cancer whose tumors had specific EGFR gene mutations (exon 19 deletions or exon 21 i.e. L858R substitution mutations) as detected by an FDA approved test.
Paclitaxel is a standard, anti-cancer medicine that has been approved by the US Food and Drug Administration (FDA) for the treatment of lung cancer.
The combination of Afatinib and Paclitaxel are considered investigational when used in this research program. An investigational drug is a drug that is not approved by the FDA for its indication.
Detailed description
Standard Procedures:
Subjects are offered second line chemotherapy with paclitaxel 80 mg/m2 intravenous infusion over 60 minutes on days 1, 8, and 15 of a 28-day cycle until disease progression or intolerable toxicity.
Experimental Procedures:
In addition to the standard chemotherapy, afatinib 40 mg orally once daily will be administered starting on the first day of paclitaxel. Translational studies to assess circulating tumor cells at the start of therapy and then at several later time points, including at the time of progression. These studies will assess the correlation of circulating tumor cell numbers with radiographic response and pilot studies will also be conducted to assess HER2 expression, HER2 genomic amplification, HER2 pathway activation and secondary genetic changes in the HER2 coding sequence as well as other pathway components.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Afatinib and weekly Paclitaxel | Experimental | Drug: Afatinib, Drug: PaclitaxelIn addition to the standard chemotherapy, afatinib 40 mg orally once daily will be administered starting on the first day of paclitaxel. Translational studies to assess circulating tumor cells at the start of therapy and then at several later time points, including at the time of progression. These studies will assess the correlation of circulating tumor cell numbers with radiographic response and pilot studies will also be conducted to assess HER2 expression, HER2 genomic amplification, HER2 pathway activation and secondary genetic changes in the HER2 coding sequence as well as other pathway components. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the intrathoracic esophagus, gastrointestinal junction or stomach.
- Tumor must be HER2 positive 3+ by immunohistochemistry or positive by Fluorescence in situ hybridization (FISH) analysis if 2+ by immunohistochemistry.
- Received and failed at least one prior cytotoxic chemotherapy regimen for advanced disease that included trastuzumab.
- Age greater than or equal to 18 years.
- At least one measurable lesion as defined by modified RECIST criteria.
Key exclusion criteria (25 listed)
- Squamous cell carcinoma.
- History of clinically relevant cardiovascular abnormalities within 6 months.
- Baseline (less than 1 month before treatment) cardiac left ventricular function with resting ejection fraction of less than 50 percent measured by multigated blood pool imaging of the heart (MUGA scan) or echocardiogram.
- Pregnant and lactating women are excluded from the study.
- Significant or recent acute gastrointestinal disorders with diarrhea.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AfatinibAlso: BIBW 2992Afatinib 40mg/PO daily will be administered in combination to standard of care paclitaxel. | Drug | Afatinib and weekly Paclitaxel |
| PaclitaxelAlso: TaxolOn the day of the first dose of afatinib, paclitaxel will be administered at a dose of 80 mg/m2 intravenously over 60 minutes on days 1, 8 and 15 of a 28-day cycle. | Drug | Afatinib and weekly Paclitaxel |
Primary outcome
Change of tumor burden (in centimeters) for participants during protocol therapy
Time frame: Change from Baseline Tumor burden, measured every 8 weeks, up to approximately 4 years
5 secondary outcomes
Number of participants with adverse events.
Time frame: up to approximately 36 months
Total number of circulating tumor cell (CTC) numbers.
Time frame: up to approximately 36 months
Clinical benefit in progression free survival.
Time frame: every 3 months up to approximately 4 years
Clinical benefit in overall survival.
Time frame: every 3 months up to approximately 4 years
ErbB2 levels benefit during therapy.
Time frame: up to approximately 4 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2017.
- Herbert Irving Comprehensive Cancer Center (HICCC) Clinical Trials PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Naiyer Rizvi, MD principal investigator
Columbia University
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Afatinib and Paclitaxel in people with HER-2 Positive Gastric Cancer and Gastrooesophageal Cancer, run by Columbia University.
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 14 inclusion and 25 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: withdrawn, as of the sponsor's last update on 14 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Change of tumor burden (in centimeters) for participants during protocol therapy (time frame: Change from Baseline Tumor burden, measured every 8 weeks, up to approximately 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Mar 2017.