HER2 Positive Esophagogastric CancerPhase 2NCT01769508
Study of 5-FU, Oxaliplatin, & Lapatinib Combined With Radiation Therapy to Treat HER2 Positive Esophagogastric Cancer
A Phase 2 study testing 5-Fluorouracil, Oxaliplatin and Lapatinib in people with HER2 Positive Esophagogastric Cancer, run by SCRI Development Innovations, LLC at 9 sites in United States.
Trial summary
With improvements in response rate and survival seen for HER2 positive patients treated with HER2 blockade in the metastatic setting, the use of HER2 blockade in the neoadjuvant setting to increase antitumor effect shows promise. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER2 Positive Esophagogastric Cancer
- What is being tested?
- 5-Fluorouracil, Oxaliplatin and Lapatinib
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 9 sitesUnited States
- Study dates
- Feb 2013to Feb 2015
- 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
- Histologically confirmed Stage I, II, or III adenocarcinoma of the esophagus (lower ⅓), GE junction, or gastric cardia.
- Clinical stage I, II, or III as assessed by required baseline staging. In addition, patients with celiac node involvement (stage IVa) are eligible.
- Patients must be surgical candidates based on stage and location of disease as well as other medical conditions and risk factors.
- Positive HER2 status (overexpression and/or amplification of HER2 in primary tumor) as defined by FISH (HER2 FISH positivity).
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.
- Patient must be able to swallow and absorb oral medication.
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- Patients must have an indwelling central venous access catheter.
- Adequate hematologic, renal, and hepatic function:
- Known brain or leptomeningeal metastases.
- Male patients willing to use adequate contraceptive measures.
- Female patients who are not of child-bearing potential, and female patients of child-bearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to start of treatment.
- Life expectancy ≥ 12 weeks.
- Age ≥18 years of age.
- Willingness and ability to comply with trial and follow-up procedures.
- Ability to understand the nature of this trial and give written informed consent.
Who cannot join
- Patients with evidence of distant metastases are ineligible, as are patients who are not potential surgical candidates based on location or extent of local disease. Patients with celiac nodal disease (Stage IVa) will be allowed on study.
- Previous anti-cancer treatment for esophageal, GE junction, or gastric cancer.
- Any other investigational agents within the 28 days prior to day 1 of the study.
- Known active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
- Concurrent treatment with drugs known to be strong inhibitors or inducers of isoenzyme CYP3A that cannot be discontinued or switched to different medication prior to starting study drug.
- Concurrent use of St. John's wort and grapefruit /grapefruit juice ≤7 days prior to starting study drug is not allowed.
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- Ongoing treatment with full-dose warfarin or its equivalent. Prophylactic treatment with 1 mg daily of warfarin and/or low molecular weight heparin is allowed.
- History of any other disease, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of a novel regimen, or that might affect interpretation of the results of this study or render the subject at high-risk for treatment complications.
- Active gastrointestinal (GI) disease or other condition that in the opinion of the investigator will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (e.g. ulcerative disease, uncontrolled nausea, or vomiting).
- Poorly controlled or clinically significant atherosclerotic vascular disease
- A serious active infection at the time of treatment, or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
- Known diagnosis of human immunodeficiency virus (HIV), Hepatitis B (HBV) or Hepatitis C (HCV).
- Presence of other active cancers, or history of treatment for invasive cancer ≤5 years. Patients with stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e. non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
- Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
- Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Chattanooga Oncology and Hematology Associates
Chattanooga, Tennessee, 37404
Oncology Hematology Care
Cincinnati, Ohio, 45242
Florida Cancer Specialists - South
Fort Myers, Florida, 33916
Northeast Georgia Medical Center
Gainesville, Georgia, 30501
Grand Rapids Oncology Program
Grand Rapids, Michigan, 49503
Tennessee Oncology
Nashville, Tennessee, 37203
Florida Hospital Cancer Institute
Orlando, Florida, 32804
Woodlands Medical Specialists
Pensacola, Florida, 32503
Florida Cancer Specialists-North
St. Petersburg, Florida, 33705
About this study
Official title: A Phase II Study With Lead-in Safety Cohort of 5-Fluorouracil, Oxaliplatin and Lapatinib in Combination With Radiation Therapy as Neoadjuvant Treatment for Patients With Localized HER2 Positive Esophagogastric Adenocarcinomas
With improvements in response rate and survival seen for HER2 positive patients treated with HER2 blockade in the metastatic setting, the use of HER2 blockade in the neoadjuvant setting to increase antitumor effect shows promise. Patients with previously untreated localized HER2 positive esophageal, GE junction and gastric adenocarcinomas will be enrolled. Patients meeting all inclusion/exclusion criteria will receive neoadjuvant treatment with concurrent chemotherapy and radiation therapy beginning on day 1 of treatment. During the lead-in safety portion, the optimal dose of lapatinib will be determined.
Read the detailed description
This is an open-label, non-randomized, Phase II study with a lead-in safety cohort. The study will evaluate the combination of 5-Fluorouracil, Oxaliplatin and Lapatinib with radiation therapy as neoadjuvant treatment for patients with previously untreated localized HER2 positive esophagogastric adenocarcinomas. Approximately 12 patients will be enrolled in the lead-in cohort to evaluate the safety of the combination. Following the lead-in cohort, Phase II will commence and up to 30 additional patients may be treated. The starting doses will be administered as follows:
5-FU 225 mg/mg2 continuous intravenous (IV) infusion Days 1 - 42 during XRT; Oxaliplatin 85 mg/m2 Days 1, 15 and 29, given by IV infusion, per institutional standard; Lapatinib Continuous PO daily dosing during XRT (final dose determined during lead-in cohort).
- Conditions
- HER2 Positive Esophagogastric Cancer
- Being tested
- 5-Fluorouracil, Oxaliplatin, Lapatinib, Radiation Therapy
- Keywords
- Esophagogastric Adenocarcinoma, 5-Fluorouracil, Oxaliplatin, Lapatinib, Radiation Therapy, Surgery
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-FluorouracilDrug
Also called Combined Modality Treatment
5-FU, 225 mg/m2 IVCI, during XRT.
OxaliplatinDrug
Also called Combined Modality Treatment
Oxaliplatin, 85 mg/m2 IV, Days 1, 15, 29.
LapatinibDrug
Also called Combined Modality Treatment
Lapatinib, Continuous PO daily dosing during XRT, dose determined during lead in portion
Radiation TherapyRadiation
Radiation therapy, 50.4 Gy (1.8 Gy/day or 28 fractions) M-F, Weeks1-6
| Study group | Role | What they receive |
|---|---|---|
| Combined Therapy | Experimental | Combined Modality Treatment of Radiation therapy, 5-Fluorouracil, Oxaliplatin and Lapatinib followed by Surgery Receives: Drug: 5-Fluorouracil; Drug: Oxaliplatin; Drug: Lapatinib; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic Complete Response Rate (pCR Rate)
Defined as the absence of invasive tumor in esophagogastric and lymph node tissue removed at time of surgery, as judged by the local pathologist. An improvement in pCR rate from 30 percent (historical) to 50 percent is the primary efficacy endpoint.
Measured: 18 months
Safety and Optimal Dose of Regimen
An additional primary objective is to evaluate the safety and optimal dose of lapatinib when added to 5-FU, oxaliplatin and radiation therapy.
Measured: 18 months
Secondary outcomes (4)
Progression Free Survival (PFS)
The Percentage of Patients Who Experience an Objective Benefit From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: 18 months
Toxicity Profile for Treated Patients
Defined as the frequency of adverse events for patients who received at least one dose of study treatment, and assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0.
Measured: 18 months
Time to Progression (TTP)
Time to progression is defined as the time between day 1 cycle 1 and time to first documented disease progression. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: 18 months
Overall Survival (OS)
The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2013 (estimated)
- Study startFeb 2013
- Primary completionFeb 2014
- Study completionFeb 2015
Why it stopped: Study closed due to slow accrual.
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 (1)Papers the sponsor has linked to this study.
- Other trials for HER2 Positive Esophagogastric CancerStudies of the same condition, open and under way.
- 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
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- SCRI Development Innovations, LLC
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Johanna C Bendell, MD, Study chair, SCRI Development Innovations, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01769508
- Sponsor's protocol ID
- SCRI GI 166
- Status last verified
- May 2016
- First submitted
- 11 Jan 2013
- Last updated
- 13 Jun 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Shepard G, Arrowsmith ER, Murphy P, Barton JH Jr, Peyton JD, Mainwaring M, Blakely L, Maun NA, Bendell JC. A Phase II Study with Lead-In Safety Cohort of 5-Fluorouracil, Oxaliplatin, and Lapatinib in Combination with Radiation Therapy as Neoadjuvant Treatment for Patients with Localized HER2-Positive Esophagogastric Adenocarcinomas. Oncologist. 2017 Oct;22(10):1152-e98. doi: 10.1634/theoncologist.2017-0186. Epub 2017 Aug 1.
PubMed 28765502
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study With Lead-in Safety Cohort of 5-Fluorouracil, Oxaliplatin and Lapatinib in Combination With Radiation Therapy as Neoadjuvant Treatment for Patients With Localized HER2 Positive Esophagogastric Adenocarcinomas
- ClinicalTrials.gov ID
- NCT01769508
- Acronym / sponsor ID
- SCRI GI 166
- Conditions
- HER2 Positive Esophagogastric Cancer
- Keywords
- Esophagogastric Adenocarcinoma, 5-Fluorouracil, Oxaliplatin, Lapatinib, Radiation Therapy, Surgery
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study closed due to slow accrual.
- Enrolment
- 12 participants (actual)
- Lead sponsor
- SCRI Development Innovations, LLCUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- Feb 2013
- Primary completion
- Feb 2014 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 16 Jan 2013 (estimated)
- Results
- Posted 27 Apr 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
With improvements in response rate and survival seen for HER2 positive patients treated with HER2 blockade in the metastatic setting, the use of HER2 blockade in the neoadjuvant setting to increase antitumor effect shows promise. Patients with previously untreated localized HER2 positive esophageal, GE junction and gastric adenocarcinomas will be enrolled. Patients meeting all inclusion/exclusion criteria will receive neoadjuvant treatment with concurrent chemotherapy and radiation therapy beginning on day 1 of treatment. During the lead-in safety portion, the optimal dose of lapatinib will be determined.
Detailed description
This is an open-label, non-randomized, Phase II study with a lead-in safety cohort. The study will evaluate the combination of 5-Fluorouracil, Oxaliplatin and Lapatinib with radiation therapy as neoadjuvant treatment for patients with previously untreated localized HER2 positive esophagogastric adenocarcinomas. Approximately 12 patients will be enrolled in the lead-in cohort to evaluate the safety of the combination. Following the lead-in cohort, Phase II will commence and up to 30 additional patients may be treated. The starting doses will be administered as follows:
5-FU 225 mg/mg2 continuous intravenous (IV) infusion Days 1 - 42 during XRT; Oxaliplatin 85 mg/m2 Days 1, 15 and 29, given by IV infusion, per institutional standard; Lapatinib Continuous PO daily dosing during XRT (final dose determined during lead-in cohort).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combined Therapy | Experimental | Drug: 5-Fluorouracil, Drug: Oxaliplatin, Drug: Lapatinib, Radiation: Radiation TherapyCombined Modality Treatment of Radiation therapy, 5-Fluorouracil, Oxaliplatin and Lapatinib followed by Surgery |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histologically confirmed Stage I, II, or III adenocarcinoma of the esophagus (lower ⅓), GE junction, or gastric cardia.
- Clinical stage I, II, or III as assessed by required baseline staging. In addition, patients with celiac node involvement (stage IVa) are eligible.
- Patients must be surgical candidates based on stage and location of disease as well as other medical conditions and risk factors.
- Positive HER2 status (overexpression and/or amplification of HER2 in primary tumor) as defined by FISH (HER2 FISH positivity).
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.
Key exclusion criteria (15 listed)
- Patients with evidence of distant metastases are ineligible, as are patients who are not potential surgical candidates based on location or extent of local disease. Patients with celiac nodal disease (Stage IVa) will be allowed on study.
- Previous anti-cancer treatment for esophageal, GE junction, or gastric cancer.
- Any other investigational agents within the 28 days prior to day 1 of the study.
- Known active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
- Concurrent treatment with drugs known to be strong inhibitors or inducers of isoenzyme CYP3A that cannot be discontinued or switched to different medication prior to starting study drug.
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 |
|---|---|---|
| 5-FluorouracilAlso: Combined Modality Treatment5-FU, 225 mg/m2 IVCI, during XRT. | Drug | Combined Therapy |
| OxaliplatinAlso: Combined Modality TreatmentOxaliplatin, 85 mg/m2 IV, Days 1, 15, 29. | Drug | Combined Therapy |
| LapatinibAlso: Combined Modality TreatmentLapatinib, Continuous PO daily dosing during XRT, dose determined during lead in portion | Drug | Combined Therapy |
| Radiation TherapyRadiation therapy, 50.4 Gy (1.8 Gy/day or 28 fractions) M-F, Weeks1-6 | Radiation | Combined Therapy |
Primary outcome
Pathologic Complete Response Rate (pCR Rate)
Time frame: 18 months
Defined as the absence of invasive tumor in esophagogastric and lymph node tissue removed at time of surgery, as judged by the local pathologist. An improvement in pCR rate from 30 percent (historical) to 50 percent is the primary efficacy endpoint.
Safety and Optimal Dose of Regimen
Time frame: 18 months
An additional primary objective is to evaluate the safety and optimal dose of lapatinib when added to 5-FU, oxaliplatin and radiation therapy.
4 secondary outcomes
Progression Free Survival (PFS)
Time frame: 18 months
Toxicity Profile for Treated Patients
Time frame: 18 months
Time to Progression (TTP)
Time frame: 18 months
Overall Survival (OS)
Time frame: 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28765502Shepard G, Arrowsmith ER, Murphy P, Barton JH Jr, Peyton JD, Mainwaring M, Blakely L, Maun NA, Bendell JC. A Phase II Study with Lead-In Safety Cohort of 5-Fluorouracil, Oxaliplatin, and Lapatinib in Combination with Radiation Therapy as Neoadjuvant Treatment for Patients with Localized HER2-Positive Esophagogastric Adenocarcinomas. Oncologist. 2017 Oct;22(10):1152-e98. doi: 10.1634/theoncologist.2017-0186. Epub 2017 Aug 1.
Related trials for HER2 Positive Esophagogastric Cancer
Not yet recruitingPhase 3
A Trial of ONO-4578 Versus Placebo in Combination With Nivolumab and Chemotherapy in Participants With Gastric Cancer, Esophagogastric Junction Cancer, or Esophageal Adenocarcinoma
Gastric Cancer, Esophagogastric Junction Cancer
Active, not recruitingPhase 2
Perioperative Chemotherapy Plus Trastuzumab Plus Toripalimab in HER2 Positive Locally Advanced Gastric or Esophagogastric Junction Adenocarcinoma
Adenocarcinoma of the Stomach, Adenocarcinoma of Esophagogastric Junction
Not yet recruitingPhase 2
Nilatinib Maleate Tablets Combined With Capecitabine in the Treatment of HER2-positive Advanced Esophageal/Esophagogastric Junction/Gastric Adenocarcinoma With Brain Metastases
Her2-positive Advanced Esophageal/Esophagogastric Junction/Gastric Adenocarcinoma With Brain Metastasis
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.
Johanna C Bendell, MD study chair
SCRI Development Innovations, LLC
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 5-Fluorouracil, Oxaliplatin and Lapatinib in people with HER2 Positive Esophagogastric Cancer, run by SCRI Development Innovations, LLC 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 15 inclusion and 15 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: stopped early, as of the sponsor's last update on 13 Jun 2016. 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 27 Apr 2016). 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?
Pathologic Complete Response Rate (pCR Rate) (time frame: 18 months). The study lists 2 primary outcomes in all. 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 NCT01769508, 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 13 Jun 2016.