Adenocarcinoma of the Gastroesophageal JunctionPhase 2NCT02234180
Regorafenib in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction Who Have Completed Chemoradiation Therapy and Surgery
A Phase 2 study testing Regorafenib in people with Adenocarcinoma of the Gastroesophageal Junction and Stage IIB Esophageal Adenocarcinoma, run by Academic and Community Cancer Research United at 10 sites in United States.
Trial summary
This randomized phase II trial studies how well regorafenib works in treating patients with cancer of the esophagus or gastroesophageal junction that has spread from where it started to nearby tissue or lymph nodes and have completed chemoradiation therapy and surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenocarcinoma of the Gastroesophageal Junction, Stage IIB Esophageal Adenocarcinoma, Stage IIIA Esophageal Adenocarcinoma
- What is being tested?
- Regorafenib
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3 participants
- Where
- 10 sitesUnited States
- Study dates
- Sep 2014to 8 Jun 2016
- 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
- Histological confirmation of node positive (any T stage N1-3) proximal esophageal, distal esophagus or gastroesophageal (GE) junction adenocarcinoma (Siewert I, II, or III) after completing preoperative chemoradiation and surgery; supporting pathology report sufficient for registration; available tumor tissue from endoscopic biopsies prior to preoperative chemotherapy (chemo)/radiation therapy (RT), and tumor from surgical specimens will be submitted to Academic and Community Cancer Research United (ACCRU), but not be required prior registration; Note: if tissue is depleted, patient will still be eligible after discussion with the physician
- Imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) =< 28 days of study registration negative for disease recurrence
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- Absolute neutrophil count (ANC) >= 1500/mm^3
- Platelet count >= 100,000/mm^3
- Total bilirubin =< 1.5 x the upper limits of normal (ULN)
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- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (=< 5 x ULN for subjects with liver involvement of their cancer)
- Alkaline phosphatase limit =< 2.5 x ULN (=< 5 x ULN for subjects with liver involvement of their cancer)
- Lipase =< 1.5 x the ULN
- Serum creatinine =< 1.5 x the ULN
- International normalized ratio (INR)/partial thromboplastin time (PTT) =< 1.5 x ULN; Note-subjects who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that their medication dose and INR/PTT are stable; close monitoring (day 1 of each cycle) is mandatory; if either of these values is above the therapeutic range, the doses should be modified and the assessments should be repeated weekly until they are stable
- Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
- Provide informed written consent
- Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
- Able to swallow and retain oral medications and begin therapy within 6 to 12 weeks post-surgery
- Provide blood samples for the mandatory correlative research purposes
Who cannot join
- Presence of metastatic or recurrent disease
- R1 or R2 resection
- Patients who have not recovered from serious adverse events (as determined by treating doctor of medicine [MD]) related to surgery
- Uncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mm Hg on repeated measurement) despite optimal medical management per physician discretion
- Active or clinically significant cardiac disease including:
- Congestive heart failure - New York Heart Association (NYHA) > class II
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- Active coronary artery disease
- Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
- Unstable angina (anginal symptoms at rest), new-onset angina < 3 months before randomization, or myocardial infarction within 6 months before randomization
- Evidence or history of bleeding diathesis or coagulopathy
- Any hemorrhage or bleeding event >= National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4 grade 3 =< 4 weeks prior to registration
- Prior cancers < 3 years, with the exception of in-situ cervical cancer, low grade prostate cancer and basal or squamous cell skin cancers
- Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) deep vein thrombosis or pulmonary embolism =< 6 months prior to registration
- Receiving any medications or substances that are strong or moderate inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4); use of strong or moderate inhibitors are prohibited =< 7 days to registration
- Receiving any medications or substances that are inducers of CYP3A4; use of inducers are prohibited =< 7 days prior to registration
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Missouri Valley Cancer Consortium
Omaha, Nebraska, 68106
Mayo Clinic
Rochester, Minnesota, 55905
Toledo Clinic Cancer Centers-Toledo
Toledo, Ohio, 43623
Carle Cancer Center
Urbana, Illinois, 61801
Cancer Center of Kansas - Wichita
Wichita, Kansas, 67214
Comprehensive Cancer Center of Wake Forest University
Winston-Salem, North Carolina, 27157
About this study
Official title: Randomized Phase II Double Blind Study of Adjuvant Regorafenib vs Placebo in Patients With Node Positive Esophageal Cancer That Completed Pre-operative Therapy
This randomized phase II trial studies how well regorafenib works in treating patients with cancer of the esophagus or gastroesophageal junction that has spread from where it started to nearby tissue or lymph nodes and have completed chemoradiation therapy and surgery. Regorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To compare the disease-free survival (DFS) for patients with resected esophageal and gastroesophageal (GE) junction adenocarcinoma treated with regorafenib vs. placebo in the adjuvant setting.
SECONDARY OBJECTIVES:
- To compare the safety profile of adjuvant regorafenib vs. placebo in patients with locally advanced resectable esophageal and GE junction adenocarcinoma.
II. To compare the overall survival (OS) for patients with resected esophageal and GE junction adenocarcinoma treated with regorafenib vs. placebo in the adjuvant setting.
III. To compare the DFS in those patients that receive at least 1 cycle of therapy.
IV. To collect tumor samples for future genomic analysis to explore the biology of locally advanced esophageal and GE junction adenocarcinoma.
- DFS will be compared between the arms from the time of surgery as well.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Within 6-12 weeks after surgery, patients receive regorafenib orally (PO) once daily (QD) on days 1-21.
ARM II: Within 6-12 weeks after surgery, patients receive placebo PO QD on days 1-21.
In both arms, courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years, and every 6 months for up to 5 years.
- Conditions
- Adenocarcinoma of the Gastroesophageal Junction, Stage IIB Esophageal Adenocarcinoma, Stage IIIA Esophageal Adenocarcinoma, Stage IIIB Esophageal Adenocarcinoma, Stage IIIC Esophageal Adenocarcinoma
- Being tested
- Placebo, Regorafenib
- Medical subject headings
- Adenocarcinoma Of Esophagus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboOther
Also called placebo therapy, PLCB, sham therapy
Given PO
RegorafenibDrug
Also called BAY 73-4506, Stivarga
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Arm I (regorafenib) | Experimental | Within 6-12 weeks after surgery, patients receive regorafenib PO QD on days 1-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Receives: Drug: Regorafenib |
| Arm II (placebo) | Placebo comparator | Within 6-12 weeks after surgery, patients receive placebo PO QD on days 1-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease Free Survival (DFS)
Disease free survival (DFS) is defined as the time from randomization to the first of either disease recurrence or death from any cause. The distribution of DFS will be estimated using the Kaplan Meier method.
Measured: Time from randomization to the first of either disease recurrence or death from any cause, assessed up to 1 year and 10 months
Secondary outcomes (2)
Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)
The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.
Measured: Up to 1 year and 10 months
Overall Survival (OS)
Overall survival (OS) is defined as the time from randomization to death due to any cause.
Measured: Time from randomization to death due to any cause, assessed up to 1 year and 10 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2014 (estimated)
- Study startSep 2014
- Primary completion8 Jun 2016
- Study completion8 Jun 2016
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.
- Other trials for Adenocarcinoma of the Gastroesophageal JunctionStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Academic and Community Cancer Research United
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Yelena Janjigian, Principal investigator, Academic and Community Cancer Research United
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02234180
- Sponsor's protocol ID
- RU021212I
- Other IDs
- NCI-2015-01699, NCI-2014-01962, RU021212I, P30CA015083
- Status last verified
- Oct 2018
- First submitted
- 4 Sep 2014
- Last updated
- 17 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase II Double Blind Study of Adjuvant Regorafenib vs Placebo in Patients With Node Positive Esophageal Cancer That Completed Pre-operative Therapy
- ClinicalTrials.gov ID
- NCT02234180
- Acronym / sponsor ID
- RU021212I
- Conditions
- Adenocarcinoma of the Gastroesophageal Junction, Stage IIB Esophageal Adenocarcinoma, Stage IIIA Esophageal Adenocarcinoma, Stage IIIB Esophageal Adenocarcinoma, Stage IIIC Esophageal Adenocarcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Academic and Community Cancer Research UnitedUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Sep 2014
- Primary completion
- 8 Jun 2016 (actual)
- Study completion
- 8 Jun 2016 (actual)
- First posted
- 9 Sep 2014 (estimated)
- Results
- Posted 17 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized phase II trial studies how well regorafenib works in treating patients with cancer of the esophagus or gastroesophageal junction that has spread from where it started to nearby tissue or lymph nodes and have completed chemoradiation therapy and surgery. Regorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES:
- To compare the disease-free survival (DFS) for patients with resected esophageal and gastroesophageal (GE) junction adenocarcinoma treated with regorafenib vs. placebo in the adjuvant setting.
SECONDARY OBJECTIVES:
- To compare the safety profile of adjuvant regorafenib vs. placebo in patients with locally advanced resectable esophageal and GE junction adenocarcinoma.
II. To compare the overall survival (OS) for patients with resected esophageal and GE junction adenocarcinoma treated with regorafenib vs. placebo in the adjuvant setting.
III. To compare the DFS in those patients that receive at least 1 cycle of therapy.
IV. To collect tumor samples for future genomic analysis to explore the biology of locally advanced esophageal and GE junction adenocarcinoma.
- DFS will be compared between the arms from the time of surgery as well.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Within 6-12 weeks after surgery, patients receive regorafenib orally (PO) once daily (QD) on days 1-21.
ARM II: Within 6-12 weeks after surgery, patients receive placebo PO QD on days 1-21.
In both arms, courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years, and every 6 months for up to 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (regorafenib) | Experimental | Drug: RegorafenibWithin 6-12 weeks after surgery, patients receive regorafenib PO QD on days 1-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. |
| Arm II (placebo) | Placebo comparator | Other: PlaceboWithin 6-12 weeks after surgery, patients receive placebo PO QD on days 1-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Histological confirmation of node positive (any T stage N1-3) proximal esophageal, distal esophagus or gastroesophageal (GE) junction adenocarcinoma (Siewert I, II, or III) after completing preoperative chemoradiation and surgery; supporting pathology report sufficient for registration; available tumor tissue from endoscopic biopsies prior to preoperative chemotherapy (chemo)/radiation therapy (RT), and tumor from surgical specimens will be submitted to Academic and Community Cancer Research United (ACCRU), but not be required prior registration; Note: if tissue is depleted, patient will still be eligible after discussion with the physician
- Imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) =< 28 days of study registration negative for disease recurrence
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- Absolute neutrophil count (ANC) >= 1500/mm^3
- Platelet count >= 100,000/mm^3
Key exclusion criteria (15 listed)
- Presence of metastatic or recurrent disease
- R1 or R2 resection
- Patients who have not recovered from serious adverse events (as determined by treating doctor of medicine [MD]) related to surgery
- Uncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mm Hg on repeated measurement) despite optimal medical management per physician discretion
- Active or clinically significant cardiac disease including:
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 |
|---|---|---|
| PlaceboAlso: placebo therapy, PLCB, sham therapyGiven PO | Other | Arm II (placebo) |
| RegorafenibAlso: BAY 73-4506, StivargaGiven PO | Drug | Arm I (regorafenib) |
Primary outcome
Disease Free Survival (DFS)
Time frame: Time from randomization to the first of either disease recurrence or death from any cause, assessed up to 1 year and 10 months
Disease free survival (DFS) is defined as the time from randomization to the first of either disease recurrence or death from any cause. The distribution of DFS will be estimated using the Kaplan Meier method.
2 secondary outcomes
Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)
Time frame: Up to 1 year and 10 months
Overall Survival (OS)
Time frame: Time from randomization to death due to any cause, assessed up to 1 year and 10 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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 principal investigator
Academic and Community Cancer Research United
10 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 Regorafenib in people with Adenocarcinoma of the Gastroesophageal Junction and Stage IIB Esophageal Adenocarcinoma, run by Academic and Community Cancer Research United at 10 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 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 17 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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. Some participants in this study may receive a placebo. 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 17 Oct 2018). 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?
Disease Free Survival (DFS) (time frame: Time from randomization to the first of either disease recurrence or death from any cause, assessed up to 1 year and 10 months). 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 17 Oct 2018.