Esophageal CancerPhase 2NCT01522768
Afatinib and Paclitaxel in Patients With Advanced HER2-Positive Trastuzumab-Refractory Advanced Esophagogastric Cancer
A Phase 2 study testing Afatinib and Paclitaxel in people with Esophageal Cancer and Gastric Cancer, run by Memorial Sloan Kettering Cancer Center at 9 sites in United States.
Trial summary
The purpose of this study is to find out what effects, good or bad, the combination of standard chemotherapy agent paclitaxel with the investigational (experimental) drug afatinib that targets HER2, has on HER2-positive esophagogastric cancer that started to get bigger despite previous treatment with trastuzumab. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Esophageal Cancer, Gastric 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
- 42 participants
- Where
- 9 sitesUnited States
- Study dates
- Mar 2012to 20 Feb 2023
- Phase
- Phase 2
- 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
- Pathologically or cytologically confirmed esophagogastric cancer.
- HER2 overexpression and/or amplification as determined by immunohistochemistry (3+) or FISH (≥2.0)
- Previously received trastuzumab as part of a regimen in the perioperative or metastatic setting with evidence of progression 9Zr-trastuzumab use as imaging agent for 89Zr-trastuzumab PET permitted..
- May have previously received lapatinib as part of a regimen in the perioperative or metastatic setting with evidence of progression of disease. Washout period for lapatinib of 14 days.
- Completion of previous chemotherapy regimen ≥2 weeks prior to the start of study treatment. Other chemotherapy regimens may have been administered between the time of progression on prior trastuzumab containing regimen and protocol therapy. No restriction on prior chemotherapy regimens for advanced stage disease.
- At least one measurable metastatic lesion according to RECIST 1.1 criteria. Ascites, pleural effusions, and bone metastases are not considered measurable. Minimum indicator lesion size = 10 mm by helical CT or = 20 mm by conventional techniques. Pathological nodes must be = 15 mm by the short axis to be considered measurable.
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- Patients aged 18 years or older, as no dosing or adverse event data are currently available on the use of afatinib in patients <18 years of age, children are excluded from this study.
- Life expectancy of at least three (3) months.
- Karnofsky performance status ≥60%
- All patients with disease technically amenable to biopsy will be asked to undergo a biopsy. Patient must agree to allow 2 biopsies of any malignant lesion that can be accessed by endoscopy or with the aid or radiology (i.e. CT guided).
- Patients who have previously provided samples at any time after trastuzumab resistance will be exempt from biopsy at the start of therapy.
- Consent to preservation of frozen and fixed samples of tumor cores for evaluation
- Able to swallow and retain oral medication.
- Negative serum HCG pregnancy test for premenopausal women of reproductive capacity and for women less than 12 months after menopause.
- Willingness to use birth control while on study.
- Asymptomatic, central nervous system metastases are permitted.
Who cannot join
- Patients receiving any concurrent anticancer therapy or investigational agents with the intention of treating esophagogastric cancer. 89Zr-trastuzumab uses as imaging agent for 89Zr-trastuzumab PET permitted.
- Prior disease progression on docetaxel or paclitaxel in metastatic setting.
- Patients who are unwilling to consent to mandatory tumor biopsy. Patients with archival tissue permitted to enroll on study per MSK Principal Investigator discretion Women who are pregnant or breast feeding.
- Concurrent radiotherapy is not permitted for disease progression on treatment on protocol (except in the context specified in section 9.0), but might be allowed for pre-existing non-target lesions with approval from the principal investigator of the trial.
- Concurrent medical conditions which may increase the risk of toxicity, including ongoing or active infection, history of significant bleeding disorder unrelated to cancer (congenital bleeding disorders, acquired bleeding disorders within one year), HIV-positive.
- Subjects with acute Hepatitis B are not eligible. Subjects with chronic hepatitis are eligible if their condition is stable and in the opinion of the investigator, if consulted, would not pose a risk to subject safety.
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- History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to study entry.
- Baseline (< 1 month before treatment) cardiac left ventricular function with resting ejection fraction of less than 50% measured by echocardiogram.
- Known pre-existing interstitial lung disease.
- Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g., Crohn's disease, malabsorption, or CTCAEGrade >2 diarrhea of any etiology.
- Unwillingness to give written informed consent, unwillingness to participate, or inability to comply with the protocol for the duration of the study.
- Active hepatitis B infection, active hepatitis C infection
- Known HIV carrier
- Known or suspected active drug or alcohol abuse. Restricted Therapies
- Additional experimental anti-cancer treatment and/or standard chemo-, immunotherapy, hormone treatment (with the exception of megestrol acetate), or concurrent radiotherapy is not allowed concomitantly with the administration of study treatment (with the exception listed in section 9.0) 89Zr-trastuzumab use as imaging agent for 89Zr-trastuzumab PET permitted. Afatinib is a substrate of P-gp and its plasma concentrations can be affected by the use of P-gp inhibitors (data on file) and it is also likely that P-gp inducers could also influence afatinib plasma concentrations.
- The use of potent P-gp inhibitors (including cyclosporine, erythromycin, ketoconazole, itraconazole, quinidine, Phenobarbital salt with quinidine, ritonavir, valspodar, verapamil) and potent P-gp inducers (including St John's wort, rifampicin) has to be avoided during treatment with afatinib. Any exemptions to this have to be discussed with the principal investigator.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Memorial Sloan Kettering Commack
Commack, New York, 11725
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
University of Southern California
Los Angeles, California, 90033
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Memorial Sloan Kettering Rockville Centre
Rockville Centre, New York
About this study
Official title: A Phase II Study of Afatinib and Paclitaxel in Patients With Advanced HER2-Positive Trastuzumab Refractory Advanced Esophagogastric Cancer
The purpose of this study is to find out what effects, good or bad, the combination of standard chemotherapy agent paclitaxel with the investigational (experimental) drug afatinib that targets HER2, has on HER2-positive esophagogastric cancer that started to get bigger despite previous treatment with trastuzumab. The doctors will also study the tumor to understand why it grew while on trastuzumab treatment and to see the effects afatinib and paclitaxel has on the tumor.
- Conditions
- Esophageal Cancer, Gastric Cancer
- Being tested
- Afatinib and Paclitaxel
- Keywords
- ESOPHAGUS, STOMACH, Afatinib, paclitaxel, trastuzumab, 11-166
- Medical subject headings
- Esophageal Neoplasms, Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Afatinib and PaclitaxelDrug
All patients receiving therapy on trial with afatinib and trastuzumab will continue on afatinib and trastuzumab until disease progression or intolerable toxicity. All additional patients will be enrolled on afatinib and paclitaxel. Patients will be treated with afatinib and paclitaxel combination. Patients will receive oral afatinib 40 mg daily plus paclitaxel 80 mg/m^2 intravenously on day 1, 8, and 15 of a 28-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Afatinib and Paclitaxel | Experimental | This is a multi-institution, open-label, non-randomized, Phase II evaluation of oral afatinib daily and intravenous paclitaxel (weekly, 3 weeks on, 1 week off) in patients with trastuzumab refractory HER2-positive metastatic or recurrent esophagogastric adenocarcinoma. An initial biopsy prior to the start of therapy is required for the correlative studies evaluating the biologic effects of afatinib. It will be obtained for all patients whose tumors are feasible to biopsy. At the site investigator's discretion, a second biopsy will also be obtained. At the discretion of the MSK Principal Investigator, select participants who show response on this study and then progress may be asked to have an optional third biopsy. Receives: Drug: Afatinib and Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy
of afatinib in patients with metastatic HER2-positive esophagogastric cancer as measured by overall clinical benefit defined as response rate (ORR) = stable disease (SD) complete response (CR) or partial response (PR) at 4 months by RECIST 1.1 criteria
Measured: 2 years
Secondary outcomes (1)
Number of Participants Evaluated for Toxicity
The type, frequency, severity, timing, and relationship of each adverse event will be determined as per the NCI Common Toxicity Criteria, version 4.0.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2012 (estimated)
- Study startMar 2012
- Primary completion20 Feb 2023
- Study completion20 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Esophageal CancerStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe 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
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Boehringer Ingelheim, University of Southern California, Dana-Farber Cancer Institute, United States Department of Defense
- Responsible party
- Sponsor
- Investigators
- Yelena Janjigian, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01522768
- Sponsor's protocol ID
- 11-166
- Status last verified
- Feb 2023
- First submitted
- 25 Jan 2012
- Last updated
- 1 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Maron SB, Chatila W, Walch H, Chou JF, Ceglia N, Ptashkin R, Do RKG, Paroder V, Pandit-Taskar N, Lewis JS, Biachi De Castria T, Sabwa S, Socolow F, Feder L, Thomas J, Schulze I, Kim K, Elzein A, Bojilova V, Zatzman M, Bhanot U, Nagy RJ, Lee J, Simmons M, Segal M, Ku GY, Ilson DH, Capanu M, Hechtman JF, Merghoub T, Shah S, Schultz N, Solit DB, Janjigian YY. Determinants of Survival with Combined HER2 and PD-1 Blockade in Metastatic Esophagogastric Cancer. Clin Cancer Res. 2023 Sep 15;29(18):3633-3640. doi: 10.1158/1078-0432.CCR-22-3769.
PubMed 37406106Sanchez-Vega F, Hechtman JF, Castel P, Ku GY, Tuvy Y, Won H, Fong CJ, Bouvier N, Nanjangud GJ, Soong J, Vakiani E, Schattner M, Kelsen DP, Lefkowitz RA, Brown K, Lacouture ME, Capanu M, Mattar M, Qeriqi B, Cecchi F, Tian Y, Hembrough T, Nagy RJ, Lanman RB, Larson SM, Pandit-Taskar N, Schoder H, Iacobuzio-Donahue CA, Ilson DH, Weber WA, Berger MF, de Stanchina E, Taylor BS, Lewis JS, Solit DB, Carrasquillo JA, Scaltriti M, Schultz N, Janjigian YY. EGFR and MET Amplifications Determine Response to HER2 Inhibition in ERBB2-Amplified Esophagogastric Cancer. Cancer Discov. 2019 Feb;9(2):199-209. doi: 10.1158/2159-8290.CD-18-0598. Epub 2018 Nov 21.
PubMed 30463996
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Afatinib and Paclitaxel in Patients With Advanced HER2-Positive Trastuzumab Refractory Advanced Esophagogastric Cancer
- ClinicalTrials.gov ID
- NCT01522768
- Acronym / sponsor ID
- 11-166
- Conditions
- Esophageal Cancer, Gastric Cancer
- Keywords
- ESOPHAGUS, STOMACH, Afatinib, paclitaxel, trastuzumab, 11-166
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Boehringer Ingelheim, University of Southern California, Dana-Farber Cancer Institute, United States Department of Defense
- Study start
- Mar 2012 (actual)
- Primary completion
- 20 Feb 2023 (actual)
- Study completion
- 20 Feb 2023 (actual)
- First posted
- 1 Feb 2012 (estimated)
- Results
- Posted 1 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to find out what effects, good or bad, the combination of standard chemotherapy agent paclitaxel with the investigational (experimental) drug afatinib that targets HER2, has on HER2-positive esophagogastric cancer that started to get bigger despite previous treatment with trastuzumab. The doctors will also study the tumor to understand why it grew while on trastuzumab treatment and to see the effects afatinib and paclitaxel has on the tumor.
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 Paclitaxel | Experimental | Drug: Afatinib and PaclitaxelThis is a multi-institution, open-label, non-randomized, Phase II evaluation of oral afatinib daily and intravenous paclitaxel (weekly, 3 weeks on, 1 week off) in patients with trastuzumab refractory HER2-positive metastatic or recurrent esophagogastric adenocarcinoma. An initial biopsy prior to the start of therapy is required for the correlative studies evaluating the biologic effects of afatinib. It will be obtained for all patients whose tumors are feasible to biopsy. At the site investigator's discretion, a second biopsy will also be obtained. At the discretion of the MSK Principal Investigator, select participants who show response on this study and then progress may be asked to have an optional third biopsy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Pathologically or cytologically confirmed esophagogastric cancer.
- HER2 overexpression and/or amplification as determined by immunohistochemistry (3+) or FISH (≥2.0)
- Previously received trastuzumab as part of a regimen in the perioperative or metastatic setting with evidence of progression 9Zr-trastuzumab use as imaging agent for 89Zr-trastuzumab PET permitted..
- May have previously received lapatinib as part of a regimen in the perioperative or metastatic setting with evidence of progression of disease. Washout period for lapatinib of 14 days.
- Completion of previous chemotherapy regimen ≥2 weeks prior to the start of study treatment. Other chemotherapy regimens may have been administered between the time of progression on prior trastuzumab containing regimen and protocol therapy. No restriction on prior chemotherapy regimens for advanced stage disease.
Key exclusion criteria (16 listed)
- Patients receiving any concurrent anticancer therapy or investigational agents with the intention of treating esophagogastric cancer. 89Zr-trastuzumab uses as imaging agent for 89Zr-trastuzumab PET permitted.
- Prior disease progression on docetaxel or paclitaxel in metastatic setting.
- Patients who are unwilling to consent to mandatory tumor biopsy. Patients with archival tissue permitted to enroll on study per MSK Principal Investigator discretion Women who are pregnant or breast feeding.
- Concurrent radiotherapy is not permitted for disease progression on treatment on protocol (except in the context specified in section 9.0), but might be allowed for pre-existing non-target lesions with approval from the principal investigator of the trial.
- Concurrent medical conditions which may increase the risk of toxicity, including ongoing or active infection, history of significant bleeding disorder unrelated to cancer (congenital bleeding disorders, acquired bleeding disorders within one year), HIV-positive.
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 |
|---|---|---|
| Afatinib and PaclitaxelAll patients receiving therapy on trial with afatinib and trastuzumab will continue on afatinib and trastuzumab until disease progression or intolerable toxicity. All additional patients will be enrolled on afatinib and paclitaxel. Patients will be treated with afatinib and paclitaxel combination. Patients will receive oral afatinib 40 mg daily plus paclitaxel 80 mg/m^2 intravenously on day 1, 8, and 15 of a 28-day cycle. | Drug | Afatinib and Paclitaxel |
Primary outcome
Efficacy
Time frame: 2 years
of afatinib in patients with metastatic HER2-positive esophagogastric cancer as measured by overall clinical benefit defined as response rate (ORR) = stable disease (SD) complete response (CR) or partial response (PR) at 4 months by RECIST 1.1 criteria
1 secondary outcome
Number of Participants Evaluated for Toxicity
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37406106Maron SB, Chatila W, Walch H, Chou JF, Ceglia N, Ptashkin R, Do RKG, Paroder V, Pandit-Taskar N, Lewis JS, Biachi De Castria T, Sabwa S, Socolow F, Feder L, Thomas J, Schulze I, Kim K, Elzein A, Bojilova V, Zatzman M, Bhanot U, Nagy RJ, Lee J, Simmons M, Segal M, Ku GY, Ilson DH, Capanu M, Hechtman JF, Merghoub T, Shah S, Schultz N, Solit DB, Janjigian YY. Determinants of Survival with Combined HER2 and PD-1 Blockade in Metastatic Esophagogastric Cancer. Clin Cancer Res. 2023 Sep 15;29(18):3633-3640. doi: 10.1158/1078-0432.CCR-22-3769.
- Derived from this study: PubMed 30463996Sanchez-Vega F, Hechtman JF, Castel P, Ku GY, Tuvy Y, Won H, Fong CJ, Bouvier N, Nanjangud GJ, Soong J, Vakiani E, Schattner M, Kelsen DP, Lefkowitz RA, Brown K, Lacouture ME, Capanu M, Mattar M, Qeriqi B, Cecchi F, Tian Y, Hembrough T, Nagy RJ, Lanman RB, Larson SM, Pandit-Taskar N, Schoder H, Iacobuzio-Donahue CA, Ilson DH, Weber WA, Berger MF, de Stanchina E, Taylor BS, Lewis JS, Solit DB, Carrasquillo JA, Scaltriti M, Schultz N, Janjigian YY. EGFR and MET Amplifications Determine Response to HER2 Inhibition in ERBB2-Amplified Esophagogastric Cancer. Cancer Discov. 2019 Feb;9(2):199-209. doi: 10.1158/2159-8290.CD-18-0598. Epub 2018 Nov 21.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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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.
Yelena Janjigian, MD principal investigator
Memorial Sloan Kettering Cancer Center
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Afatinib and Paclitaxel in people with Esophageal Cancer and Gastric Cancer, run by Memorial Sloan Kettering Cancer Center at 9 sites in United States.
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 16 inclusion and 16 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 1 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. 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 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?
Yes. Results are posted in the registry (first posted 1 Nov 2023). 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?
Efficacy (time frame: 2 years). 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 NCT01522768, which also lists 2 linked publications.
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 1 Nov 2023.