Sorafenib for Patients With Metastatic or Recurrent Esophageal and Gastroesophageal Junction Cancer

Sponsor
Memorial Sloan Kettering Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT00917462
Collaborator
Bayer (Industry)
35
1
1
110
0.3

Study Details

Study Description

Brief Summary

Sorafenib is a drug being studied for the treatment of cancer. Sorafenib has been shown to block certain proteins on the surface of some cancer cells called "growth factor receptors." Blocking these growth factor receptors can slow or stop cancer cell growth.

Sorafenib is also known as Nexavar®. It has been studied in other types of cancers, including kidney cancer, and has been approved by the Food and Drug Administration (FDA) for treating advanced kidney cancer. Because it is not approved by the FDA for treating esophageal cancer, it is considered an experimental treatment.

The purpose of this study is to determine what effects sorafenib has on advanced esophageal cancer. These effects include whether sorafenib can shrink the tumor or slow down its growth and what side effects sorafenib will have on the tumor.

Condition or Disease Intervention/Treatment Phase
  • Drug: Sorafenib, administered orally
  • Procedure: CT/MRI
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
35 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Trial of Sorafenib for Patients With Metastatic or Recurrent Esophageal and Gastroesophageal Junction Cancer
Actual Study Start Date :
Jun 1, 2009
Actual Primary Completion Date :
Aug 1, 2018
Actual Study Completion Date :
Aug 1, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Sorafenib

Sorafenib for patients with metastatic or recurrent esophageal and gastroesophageal junction cancer.

Drug: Sorafenib, administered orally
Sorafenib 400 mg twice daily administered continuously. Patients will continue on treatment until progression of disease. Each cycle consists of 28 days. The cycle start date will coincide with the physician visit date. Because of the potential need for physician visit scheduling to vary (due to both physician and patient issues), to avoid violation of, and deviation from, the protocol, these visits may vary by up to one to fourteen (1-14) days. A study diary will be completed by patients to ensure compliance with the study drug.

Procedure: CT/MRI
A CT (computerized tomography) or MRI (magnetic resonance imaging) scan of the chest and abdomen will be obtained at baseline, after the first four weeks of therapy, at eight weeks, and then every eight weeks there afterwith a scheduling window of up to one to fourteen (1-14) days. The same imaging modality performed at baseline (CT or MRI) will be repeated at subsequent imaging.

Outcome Measures

Primary Outcome Measures

  1. 2-month Progression-free Survival (PFS) of Sorafenib in Patients With Metastatic or Recurrent Esophageal and Gastroesophageal (GE) Junction Cancer. [2 months]

Secondary Outcome Measures

  1. Overall Response Rate (Partial Response and Complete Response) of Sorafenib. [after the first four weeks of therapy, at eight weeks, and every eight weeks thereafter, an average of 1 year]

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: 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.

  2. Number of Participants With Adverse Events [every week while on study]

  3. Exploratory Analysis of Differential Response Between Squamous Cell Carcinoma and Adenocarcinoma. [2 years]

  4. Percentage of Tumors With High Phosphorylated Extracellular Signal-regulated Kinase Expression [anytime prior to enrollment or during protocol therapy]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Patients must have histologically proven or cytologically confirmed esophageal cancer (squamous cell carcinoma or adenocarcinoma) or adenocarcinoma of the gastroesophageal (GE) junction documented at MSKCC.

  • Metastatic disease measurable on a CT or MRI scan. Locally recurrent disease that is not amenable to potentially curative surgery or radiation therapy is also allowed. Lesions must be ≥ 10 mm in size. The primary tumor is not considered measurable disease. Recurrent or metastatic lesions within a prior radiation field are acceptable as long as disease has progressed in the radiation field by RECIST criteria. The same imaging modality performed at baseline (CT or MRI) will be repeated at subsequent imaging.

  • Patients are allowed to have a maximum of two prior chemotherapy regimens for metastatic disease. Patients are allowed to have a maximum of three prior regimens if they also previously received neoadjuvant/adjuvant chemotherapy or chemoradiotherapy. The last treatment must have been administered > 3 weeks prior to initiation of therapy with sorafenib.

  • Pathologic tissue must be available for immunohistochemistry (IHC) staining for phosphorylated extracellular signal-regulated kinase (pERK). Both patients with and without pERK staining are eligible for treatment. Submission of slides and IHC testing for pERK may be done during the course of therapy and are not required prior to protocol therapy.

  • Age ≥ 18 years.

  • Life expectancy > 3 months.

  • Karnofsky performance status ≥ 60%.

  • Patients must have the ability to comprehend and willingness to sign an informed consent document.

  • At baseline, patients must have normal organ and marrow function as defined:

  • Adequate bone marrow, liver and renal function as assessed by the following:

  • Hemoglobin ≥ 9.0 g/dl

  • Absolute neutrophil count (ANC) ≥ 1,500/mm3

  • Platelet count ≥ 100,000/mm3

  • Total bilirubin ≤ 1.5 times ULN

  • ALT and AST ≤ 2.5 times the ULN ( < or = to 5 x ULN for patients with liver involvement)

  • Creatinine ≤ 1.5 times ULN

Exclusion Criteria:
  • Patients who have not recovered from adverse events related to therapy administered > 3 weeks earlier. This does not include hemoglobin or other hematologic or laboratory criteria.

  • Patients may not be receiving any other investigational agents.

  • Prior therapy with sorafenib-related compounds or compounds of similar biologic or chemical components, including compounds targeting VEGF, VEGF-R or RAF kinase.

  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, greater than New York Heart Association (NYHA) Class II congestive heart failure, unstable or new onset angina pectoris or myocardial infarction within the past six months, unstable arrhythmia, or psychiatric illness/social situation, e.g., severe schizophrenia, that would limit compliance with study requirements. Patients with chronic arrhythmias, such as paroxysmal atrial fibrillation or paroxysmal supraventricular tachycardia, are eligible.

  • Uncontrolled hypertension, defined as systolic blood pressure > 150 mmHg or diastolic blood pressure > 90 mmHg, despite optimal medical management.

  • Thrombotic or embolic event, including cerebrovascular accident or transient ischemic attack within the past six months. Patients with prior deep vein thromboses or pulmonary emboli on a stable anticoagulation regimen will be eligible for enrollment.

  • Any factor that would significantly interfere with the inability to consume or absorb an oral medication, e.g. severe nausea/vomiting not controlled by an aggressive anti-emetic regimen, grade 3/4 dysphagia, extensive small bowel resection or active inflammatory bowel disease leading to chronic malabsorption. Patients with enteral feeding tubes are eligible as sorafenib can be crushed.

  • Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C infection.

  • Patients with any other concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for participation in the study.

  • Patients who are taking St. John's wort or rifampin (as there may be drug-drug interactions with sorafenib.

  • Patients with known brain metastases or meningeal carcinomatosis are excluded. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.

  • Pregnant women are excluded because sorafenib has the potential for teratogenic or abortifacient effects. Female patients must either not be of childbearing potential or must have a negative pregnancy test ≤ 7 days prior to treatment. Female patients are considered not of childbearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or if they are post-menopausal. Men must use effective birth control if their partners are of child-bearing potential.

  • No other malignancy is allowed except for adequately treated carcinoma in-situ of the cervix, superficial transitional cell carcinoma of the bladder or basal/squamous cell skin cancer. Other cancers are permissible if the patient has been disease free for ≥ 3 years.

  • Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks of first dose of study drug.

  • Any other hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks of first dose of study drug.

  • Serious non-healing wound, ulcer, or bone fracture.

  • Evidence or history of bleeding diathesis or coagulopathy.

  • Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.

  • Known or suspected allergy to sorafenib or any agent given in the course of this trial.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Memorial Sloan Kettering Cancer Center New York New York United States 10065

Sponsors and Collaborators

  • Memorial Sloan Kettering Cancer Center
  • Bayer

Investigators

  • Principal Investigator: David Ilson, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00917462
Other Study ID Numbers:
  • 09-016
First Posted:
Jun 10, 2009
Last Update Posted:
Mar 27, 2019
Last Verified:
Aug 1, 2018
Keywords provided by Memorial Sloan Kettering Cancer Center
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Sorafenib
Arm/Group Description Sorafenib for patients with metastatic or recurrent esophageal and gastroesophageal junction cancer. Sorafenib, administered orally: Sorafenib 400 mg twice daily administered continuously. Patients will continue on treatment until progression of disease. Each cycle consists of 28 days. The cycle start date will coincide with the physician visit date. Because of the potential need for physician visit scheduling to vary (due to both physician and patient issues), to avoid violation of, and deviation from, the protocol, these visits may vary by up to one to fourteen (1-14) days. A study diary will be completed by patients to ensure compliance with the study drug.
Period Title: Overall Study
STARTED 35
COMPLETED 34
NOT COMPLETED 1

Baseline Characteristics

Arm/Group Title Sorafenib
Arm/Group Description Sorafenib for patients with metastatic or recurrent esophageal and gastroesophageal junction cancer. Sorafenib, administered orally: Sorafenib 400 mg twice daily administered continuously. Patients will continue on treatment until progression of disease. Each cycle consists of 28 days. The cycle start date will coincide with the physician visit date. Because of the potential need for physician visit scheduling to vary (due to both physician and patient issues), to avoid violation of, and deviation from, the protocol, these visits may vary by up to one to fourteen (1-14) days. A study diary will be completed by patients to ensure compliance with the study drug.
Overall Participants 35
Age (years) [Median (Full Range) ]
Median (Full Range) [years]
62
Sex: Female, Male (Count of Participants)
Female
4
11.4%
Male
31
88.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
1
2.9%
Not Hispanic or Latino
34
97.1%
Unknown or Not Reported
0
0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
Asian
3
8.6%
Native Hawaiian or Other Pacific Islander
0
0%
Black or African American
0
0%
White
31
88.6%
More than one race
0
0%
Unknown or Not Reported
1
2.9%
Region of Enrollment (Count of Participants)
United States
35
100%

Outcome Measures

1. Primary Outcome
Title 2-month Progression-free Survival (PFS) of Sorafenib in Patients With Metastatic or Recurrent Esophageal and Gastroesophageal (GE) Junction Cancer.
Description
Time Frame 2 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Sorafenib
Arm/Group Description Sorafenib for patients with metastatic or recurrent esophageal and gastroesophageal junction cancer. Sorafenib, administered orally: Sorafenib 400 mg twice daily administered continuously. Patients will continue on treatment until progression of disease. Each cycle consists of 28 days. The cycle start date will coincide with the physician visit date. Because of the potential need for physician visit scheduling to vary (due to both physician and patient issues), to avoid violation of, and deviation from, the protocol, these visits may vary by up to one to fourteen (1-14) days. A study diary will be completed by patients to ensure compliance with the study drug.
Measure Participants 35
Progression Free
20
57.1%
Progressed
14
40%
Not evaluable
1
2.9%
2. Secondary Outcome
Title Overall Response Rate (Partial Response and Complete Response) of Sorafenib.
Description Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: 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.
Time Frame after the first four weeks of therapy, at eight weeks, and every eight weeks thereafter, an average of 1 year

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Sorafenib
Arm/Group Description Sorafenib for patients with metastatic or recurrent esophageal and gastroesophageal junction cancer. Sorafenib, administered orally: Sorafenib 400 mg twice daily administered continuously. Patients will continue on treatment until progression of disease. Each cycle consists of 28 days. The cycle start date will coincide with the physician visit date. Because of the potential need for physician visit scheduling to vary (due to both physician and patient issues), to avoid violation of, and deviation from, the protocol, these visits may vary by up to one to fourteen (1-14) days. A study diary will be completed by patients to ensure compliance with the study drug.
Measure Participants 35
Disease Progression
14
40%
Stable Disease
19
54.3%
Complete Response
1
2.9%
Not Evaluable
1
2.9%
3. Secondary Outcome
Title Number of Participants With Adverse Events
Description
Time Frame every week while on study

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Sorafenib
Arm/Group Description Sorafenib for patients with metastatic or recurrent esophageal and gastroesophageal junction cancer. Sorafenib, administered orally: Sorafenib 400 mg twice daily administered continuously. Patients will continue on treatment until progression of disease. Each cycle consists of 28 days. The cycle start date will coincide with the physician visit date. Because of the potential need for physician visit scheduling to vary (due to both physician and patient issues), to avoid violation of, and deviation from, the protocol, these visits may vary by up to one to fourteen (1-14) days. A study diary will be completed by patients to ensure compliance with the study drug.
Measure Participants 35
Count of Participants [Participants]
35
100%
4. Secondary Outcome
Title Exploratory Analysis of Differential Response Between Squamous Cell Carcinoma and Adenocarcinoma.
Description
Time Frame 2 years

Outcome Measure Data

Analysis Population Description
Data were not collected
Arm/Group Title Sorafenib
Arm/Group Description Sorafenib for patients with metastatic or recurrent esophageal and gastroesophageal junction cancer. Sorafenib, administered orally: Sorafenib 400 mg twice daily administered continuously. Patients will continue on treatment until progression of disease. Each cycle consists of 28 days. The cycle start date will coincide with the physician visit date. Because of the potential need for physician visit scheduling to vary (due to both physician and patient issues), to avoid violation of, and deviation from, the protocol, these visits may vary by up to one to fourteen (1-14) days. A study diary will be completed by patients to ensure compliance with the study drug.
Measure Participants 0
5. Secondary Outcome
Title Percentage of Tumors With High Phosphorylated Extracellular Signal-regulated Kinase Expression
Description
Time Frame anytime prior to enrollment or during protocol therapy

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Sorafenib
Arm/Group Description Sorafenib for patients with metastatic or recurrent esophageal and gastroesophageal junction cancer. Sorafenib, administered orally: Sorafenib 400 mg twice daily administered continuously. Patients will continue on treatment until progression of disease. Each cycle consists of 28 days. The cycle start date will coincide with the physician visit date. Because of the potential need for physician visit scheduling to vary (due to both physician and patient issues), to avoid violation of, and deviation from, the protocol, these visits may vary by up to one to fourteen (1-14) days. A study diary will be completed by patients to ensure compliance with the study drug.
Measure Participants 35
Number [% of tumors with high pERK expression]
65

Adverse Events

Time Frame Up to 2 years
Adverse Event Reporting Description
Arm/Group Title Sorafenib
Arm/Group Description Sorafenib for patients with metastatic or recurrent esophageal and gastroesophageal junction cancer. Sorafenib, administered orally: Sorafenib 400 mg twice daily administered continuously. Patients will continue on treatment until progression of disease. Each cycle consists of 28 days. The cycle start date will coincide with the physician visit date. Because of the potential need for physician visit scheduling to vary (due to both physician and patient issues), to avoid violation of, and deviation from, the protocol, these visits may vary by up to one to fourteen (1-14) days. A study diary will be completed by patients to ensure compliance with the study drug.
All Cause Mortality
Sorafenib
Affected / at Risk (%) # Events
Total 35/35 (100%)
Serious Adverse Events
Sorafenib
Affected / at Risk (%) # Events
Total 15/35 (42.9%)
Cardiac disorders
Sinus Tachycardia 1/35 (2.9%)
Gastrointestinal disorders
Constipation 1/35 (2.9%)
Dry Mouth 1/35 (2.9%)
Dysphagia 1/35 (2.9%)
Fistula - GI, Esophagus 2/35 (5.7%)
Vomiting 1/35 (2.9%)
General disorders
Constitutional Symptoms, Other 1/35 (2.9%)
Edema: viscera 1/35 (2.9%)
Fatigue 2/35 (5.7%)
Fever 1/35 (2.9%)
Pain - Other 1/35 (2.9%)
Rigors/Chills 1/35 (2.9%)
Infections and infestations
Pleural Infection 1/35 (2.9%)
Investigations
Hyperbilirubinemia 1/35 (2.9%)
Metabolism and nutrition disorders
Hypercalcemia 1/35 (2.9%)
Dehydration 4/35 (11.4%)
Musculoskeletal and connective tissue disorders
Pain - Chest Wall 1/35 (2.9%)
Pain in extremity 1/35 (2.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary malignancy 1/35 (2.9%)
Nervous system disorders
Motor neuropathy 2/35 (5.7%)
Psychiatric disorders
Confusion 2/35 (5.7%)
Renal and urinary disorders
Renal/Genitourinary - Other 1/35 (2.9%)
Respiratory, thoracic and mediastinal disorders
Cough 1/35 (2.9%)
Dyspnea 1/35 (2.9%)
Pleural effusion 1/35 (2.9%)
Pneumonitis 1/35 (2.9%)
Vascular disorders
Hypertension 1/35 (2.9%)
Thrombosis/Thrombus/Embolism 1/35 (2.9%)
Other (Not Including Serious) Adverse Events
Sorafenib
Affected / at Risk (%) # Events
Total 34/35 (97.1%)
Blood and lymphatic system disorders
Hemoglobin/Anemia 9/35 (25.7%)
Gastrointestinal disorders
Diarrhea 18/35 (51.4%)
Nausea 12/35 (34.3%)
Vomiting 6/35 (17.1%)
Constipation 5/35 (14.3%)
Mucositis 4/35 (11.4%)
General disorders
Fatigue 30/35 (85.7%)
Fever 3/35 (8.6%)
Injury, poisoning and procedural complications
Rash/desquamation 4/35 (11.4%)
Investigations
Weight Loss 5/35 (14.3%)
Platelets 4/35 (11.4%)
ALT/Alkaline phosphatase increased 3/35 (8.6%)
AST/Aspartate aminotransferase increased 3/35 (8.6%)
Alkaline Phosphatase 3/35 (8.6%)
INR 3/35 (8.6%)
Lymphopenia 3/35 (8.6%)
Creatinine 2/35 (5.7%)
Leukocytes 2/35 (5.7%)
Lipase 2/35 (5.7%)
Metabolism and nutrition disorders
Albumin, low 9/35 (25.7%)
Anorexia 9/35 (25.7%)
Hyperglycemia 7/35 (20%)
Hyponatremia 4/35 (11.4%)
Nervous system disorders
Sensory Neuropathy 4/35 (11.4%)
Respiratory, thoracic and mediastinal disorders
Dyspnea 4/35 (11.4%)
Cough 2/35 (5.7%)
Skin and subcutaneous tissue disorders
Dermatology/Skin - other 10/35 (28.6%)
Dry Skin 8/35 (22.9%)
Rash: hand-foot skin reaction 8/35 (22.9%)
Alopecia 4/35 (11.4%)
Pain - scalp 2/35 (5.7%)
Pain - skin 2/35 (5.7%)
Vascular disorders
Hypertension 2/35 (5.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Dr. David Ilson, MD, PhD
Organization Memorial Sloan Kettering Cancer Center
Phone 646-888-4183
Email ilsond@mskcc.org
Responsible Party:
Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00917462
Other Study ID Numbers:
  • 09-016
First Posted:
Jun 10, 2009
Last Update Posted:
Mar 27, 2019
Last Verified:
Aug 1, 2018