Panitumumab, Combination Chemotherapy, and Radiation Therapy Before Surgery in Treating Patients With Advanced Esophageal or Gastroesophageal Junction Cancer

• Sponsor: University of Nebraska (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01307956
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 11
• Location: 1
• Arm: 1
• Duration (Months): 99.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This phase II trial is studying how well giving panitumumab, combination chemotherapy, and radiation therapy together before surgery works in treating patients with advanced esophageal or gastroesophageal (GE) junction cancer. Monoclonal antibodies, such as panitumumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as oxaliplatin, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells. Giving monoclonal antibody therapy together with chemotherapy and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Gastroesophageal Junction; Esophageal Adenocarcinoma; Stage IIA Esophageal Cancer; Stage IIB Esophageal Cancer	Drug: Fluorouracil; Other: Laboratory Biomarker Analysis; Drug: Leucovorin Calcium; Drug: Oxaliplatin; Biological: Panitumumab; Other: Pharmacological Study; Radiation: Radiation Therapy; Procedure: Therapeutic Conventional Surgery	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the pathologic complete response rate of a modified FOLFOX-6 regimen (leucovorin calcium, fluorouracil, and oxaliplatin) given with panitumumab at two-week intervals x 4 cycles in combination with external beam radiation therapy for patients with locally advanced adenocarcinoma of the esophagus.

SECONDARY OBJECTIVES:

1. To determine the toxicities and ability to complete the planned treatment. II. To determine the achieved steady-state plasma concentrations of 5-FU (fluorouracil) and correlate these with clinical toxicity.

2. To assess the potential importance of polymorphic variations in genomic deoxyribonucleic acid (DNA) of pertinent genes whose protein products are the targets of the anti-neoplastic drugs used in the clinical protocol on response and toxicity to therapy.

OUTLINE:

Patients receive panitumumab intravenously (IV) over 1 hour on day 1. Patients also receive oxaliplatin IV and leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on day 1 (FOLFOX chemotherapy). Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Within 24 hours of the start of chemotherapy, patients undergo radiation therapy 5 days a week for 5.5 weeks. Patients then undergo surgery within 6-8 weeks after completion of radiation therapy. Patients with residual disease receive 4 additional courses of FOLFOX chemotherapy on days 1, 15, 29, and 42.

After completion of study treatment, patients are followed up every 3 months for 2 years and then annually thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Neo-adjuvant Therapy With Oxaliplatin, Leucovorin, 5-Fluorouracil, Panitumumab (Vectibix) and Radiation in Patients With Locally Advanced Adenocarcinoma of the Esophagus or Gastroesophageal Junction
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jun 1, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (panitumumab, chemotherapy, radiation) Patients receive panitumumab IV over 1 hour on day 1. Patients also receive oxaliplatin IV and leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on day 1 (FOLFOX chemotherapy). Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Within 24 hours of the start of chemotherapy, patients undergo radiation therapy 5 days a week for 5.5 weeks. Patients then undergo surgery within 6-8 weeks after completion of radiation therapy. Patients with residual disease receive 4 additional courses of FOLFOX chemotherapy on days 1, 15, 29, and 42.

Drug: Fluorouracil; Given IV; Other Names: 5-Fluoro-2,4(1H, 3H)-pyrimidinedione 5-Fluorouracil 5-Fluracil 5-FU AccuSite Carac Fluoro Uracil Fluouracil Flurablastin Fluracedyl Fluracil Fluril Fluroblastin Ribofluor Ro 2-9757 Ro-2-9757 ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Leucovorin Calcium; Given IV; Other Names: Adinepar Calcifolin Calcium (6S)-Folinate Calcium Folinate Calcium Leucovorin Calfolex Calinat Cehafolin Citofolin Citrec Citrovorum Factor Cromatonbic Folinico Dalisol Disintox Divical Ecofol Emovis Factor, Citrovorum Flynoken A Folaren Folaxin FOLI-cell Foliben Folidan Folidar Folinac Folinate Calcium folinic acid Folinic Acid Calcium Salt Pentahydrate Folinoral Folinvit Foliplus Folix Imo Lederfolat Lederfolin Leucosar leucovorin Rescufolin Rescuvolin Tonofolin Wellcovorin ; Drug: Oxaliplatin; Given IV; Other Names: 1-OHP Ai Heng Aiheng Dacotin Dacplat Diaminocyclohexane Oxalatoplatinum Eloxatin Eloxatine JM-83 Oxalatoplatin Oxalatoplatinum RP 54780 RP-54780 SR-96669 ; Biological: Panitumumab; Given IV; Other Names: ABX-EGF ABX-EGF Monoclonal Antibody ABX-EGF, Clone E7.6.3 MoAb ABX-EGF Monoclonal Antibody ABX-EGF Vectibix ; Other: Pharmacological Study; Correlative studies; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy Irradiate Irradiated Irradiation RADIATION Radiotherapeutics Radiotherapy RT Therapy, Radiation ; Procedure: Therapeutic Conventional Surgery; Undergo surgical resection

Outcome Measures

Primary Outcome Measures

1. Complete Pathological Response (pCR) Rate [Up to 8 weeks]

   Based on the proportion who achieve pCR based on the first 4 courses of protocol treatment. Evaluated using the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 guidelines. Means (with associated standard errors), medians (with ranges), percentages and 95% confidence intervals will be reported as appropriate.

Secondary Outcome Measures

1. Number of Patients Who Can Undergo Resection [4 weeks after completion of the radiation]

   Restaging with repeat imaging studies will be performed. If no contraindication for surgical resection is identified, resection will be performed. Means (with associated standard errors), medians (with ranges), percentages and 95% confidence intervals will be reported as appropriate.

Other Outcome Measures

1. Progression-free Survival [Patients were followed from time of consent until the date of first documented progession or date of death from any cause, whichever came first, assessed up to 100 months.]

   Descriptively summarized using the method of Kaplan-Meier. Response and disease progression were assessed using RECIST criteria version 1.1

2. Overall Survival [From the first date of therapy until the date the patient dies, assessed up to 100 months]

   Descriptively summarized using the method of Kaplan-Meier.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have resectable adenocarcinoma of the esophagus or GE-junction and are medically fit to undergo surgery; patients must have no evidence of distant metastasis based on imaging studies

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Absolute neutrophil count (ANC) of at least 2000 per mcL

• Platelet count of at least 100,000 per mcL

• Serum creatinine less than or equal to 2.0 mg/dL

• Serum magnesium greater than or equal to 1.8 mg/dL

• Total bilirubin less than or equal to 2.0 mg per dL

• Measurable disease is not required for this study, since the primary endpoint is complete pathologic response

• The patient must be aware of the neoplastic nature of his/her disease and willingly provide written, informed consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts

Exclusion Criteria:

• Prior therapy: patients with prior history of mediastinal radiation exposure will be ineligible; patients may not have received prior chemotherapy, or antibody therapy for esophageal or GE-junction adenocarcinoma

• History of allergy to platinum compounds or to antiemetics appropriate for administration in conjunction with protocol-directed chemotherapy

• Patients with a prior history of marked intolerance to 5-fluoropyrimidines (5-FU, floxuridine, capecitabine, 5-fluorocytosine [flucytosine]), since such patients may have deficiency of dihydropyrimidine dehydrogenase, which places them at risk for severe and life-threatening toxicity with 5-FU

• Uncontrolled inter-current illness including, but not limited to ongoing or active infection requiring intravenous antibiotics, ongoing immunosuppressive therapy (except for replacement steroids), active human immunodeficiency virus (HIV) infection, that might jeopardize the ability of the patient to receive the chemotherapy program outlined in this protocol with reasonable safety

• Clinically significant cardiac disease (including symptomatic congestive heart failure, myocardial infarction, unstable angina pectoris, or serious, uncontrolled cardiac arrhythmia) within 1 year of study enrollment

• Pregnant and nursing women, or women planning to become pregnant within 6 months after the end of treatment, are excluded from this study; a negative pregnancy test will be required of women of child-bearing age within 72 hours of study enrollment; subjects (male or female) who are not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment are excluded

• History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest computed tomography (CT) scan

• Patients with prior malignancy will be excluded except for adequately treated basal cell or squamous cell skin cancer, adequately treated noninvasive carcinomas, or other cancers from which the patient has been disease-free for at least 5 years

• Patients receiving an investigational agent within 30 days before enrollment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198

Sponsors and Collaborators

• University of Nebraska
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Jean Grem, University of Nebraska

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jean Grem, MD, Principal Investigator, University of Nebraska
• ClinicalTrials.gov Identifier: NCT01307956
• Other Study ID Numbers: 221-09; NCI-2010-02056; 221-09; P30CA036727
• First Posted: Mar 3, 2011
• Last Update Posted: Sep 30, 2019
• Last Verified: Sep 1, 2019

• Additional relevant MeSH terms: Adenocarcinoma; Esophageal Neoplasms; Calcium, Dietary; Leucovorin; Folic Acid; Antineoplastic Agents, Immunological; Panitumumab; Fluorouracil; Oxaliplatin; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Calcium; Levoleucovorin

Study Results

Participant Flow

Arm/Group Title	Treatment (Panitumumab, Chemotherapy, Radiation)
Arm/Group Description	Patients receive panitumumab IV over 1 hour on day 1. Patients also receive oxaliplatin IV and leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on day 1 (FOLFOX chemotherapy). Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Within 24 hours of the start of chemotherapy, patients undergo radiation therapy 5 days a week for 5.5 weeks. Patients then undergo surgery within 6-8 weeks after completion of radiation therapy. Patients with residual disease receive 4 additional courses of FOLFOX chemotherapy on days 1, 15, 29, and 42.
Period Title: Overall Study
STARTED	11
COMPLETED	11
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Panitumumab, Chemotherapy, Radiation)
Arm/Group Description	Patients receive panitumumab IV over 1 hour on day 1. Patients also receive oxaliplatin IV and leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on day 1 (FOLFOX chemotherapy). Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Within 24 hours of the start of chemotherapy, patients undergo radiation therapy 5 days a week for 5.5 weeks. Patients then undergo surgery within 6-8 weeks after completion of radiation therapy. Patients with residual disease receive 4 additional courses of FOLFOX chemotherapy on days 1, 15, 29, and 42.
Overall Participants	11
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	8 72.7%
>=65 years	3 27.3%
Sex: Female, Male (Count of Participants)
Female	1 9.1%
Male	10 90.9%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	10 90.9%
Asian/Pacific Islander	1 9.1%
Region of Enrollment (participants) [Number]
United States	11 100%

Outcome Measures

1. Primary Outcome

Title	Complete Pathological Response (pCR) Rate
Description	Based on the proportion who achieve pCR based on the first 4 courses of protocol treatment. Evaluated using the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 guidelines. Means (with associated standard errors), medians (with ranges), percentages and 95% confidence intervals will be reported as appropriate.
Time Frame	Up to 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Panitumumab, Chemotherapy, Radiation)
Arm/Group Description	Patients receive panitumumab IV over 1 hour on day 1. Patients also receive oxaliplatin IV and leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on day 1 (FOLFOX chemotherapy). Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Within 24 hours of the start of chemotherapy, patients undergo radiation therapy 5 days a week for 5.5 weeks. Patients then undergo surgery within 6-8 weeks after completion of radiation therapy. Patients with residual disease receive 4 additional courses of FOLFOX chemotherapy on days 1, 15, 29, and 42.
Measure Participants	11
Count of Participants [Participants]	3 27.3%

2. Secondary Outcome

Title	Number of Patients Who Can Undergo Resection
Description	Restaging with repeat imaging studies will be performed. If no contraindication for surgical resection is identified, resection will be performed. Means (with associated standard errors), medians (with ranges), percentages and 95% confidence intervals will be reported as appropriate.
Time Frame	4 weeks after completion of the radiation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Panitumumab, Chemotherapy, Radiation)
Arm/Group Description	Patients receive panitumumab IV over 1 hour on day 1. Patients also receive oxaliplatin IV and leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on day 1 (FOLFOX chemotherapy). Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Within 24 hours of the start of chemotherapy, patients undergo radiation therapy 5 days a week for 5.5 weeks. Patients then undergo surgery within 6-8 weeks after completion of radiation therapy. Patients with residual disease receive 4 additional courses of FOLFOX chemotherapy on days 1, 15, 29, and 42.
Measure Participants	11
Count of Participants [Participants]	11 100%

3. Other Pre-specified Outcome

Title	Progression-free Survival
Description	Descriptively summarized using the method of Kaplan-Meier. Response and disease progression were assessed using RECIST criteria version 1.1
Time Frame	Patients were followed from time of consent until the date of first documented progession or date of death from any cause, whichever came first, assessed up to 100 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Panitumumab, Chemotherapy, Radiation)
Arm/Group Description	Patients receive panitumumab IV over 1 hour on day 1. Patients also receive oxaliplatin IV and leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on day 1 (FOLFOX chemotherapy). Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Within 24 hours of the start of chemotherapy, patients undergo radiation therapy 5 days a week for 5.5 weeks. Patients then undergo surgery within 6-8 weeks after completion of radiation therapy. Patients with residual disease receive 4 additional courses of FOLFOX chemotherapy on days 1, 15, 29, and 42.
Measure Participants	11
Median (Full Range) [days]	409

4. Other Pre-specified Outcome

Title	Overall Survival
Description	Descriptively summarized using the method of Kaplan-Meier.
Time Frame	From the first date of therapy until the date the patient dies, assessed up to 100 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Panitumumab, Chemotherapy, Radiation)
Arm/Group Description	Patients receive panitumumab IV over 1 hour on day 1. Patients also receive oxaliplatin IV and leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on day 1 (FOLFOX chemotherapy). Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Within 24 hours of the start of chemotherapy, patients undergo radiation therapy 5 days a week for 5.5 weeks. Patients then undergo surgery within 6-8 weeks after completion of radiation therapy. Patients with residual disease receive 4 additional courses of FOLFOX chemotherapy on days 1, 15, 29, and 42.
Measure Participants	11
Median (Full Range) [days]	596

Adverse Events

Time Frame	Patients were followed for adverse events from the time of first treatment until they 30 days after last day of study treatment. (approximately 10 weeks)
Arm/Group Title	Treatment (Panitumumab, Chemotherapy, Radiation)
Arm/Group Description	Patients receive panitumumab IV over 1 hour on day 1. Patients also receive oxaliplatin IV and leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on day 1 (FOLFOX chemotherapy). Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Within 24 hours of the start of chemotherapy, patients undergo radiation therapy 5 days a week for 5.5 weeks. Patients then undergo surgery within 6-8 weeks after completion of radiation therapy. Patients with residual disease receive 4 additional courses of FOLFOX chemotherapy on days 1, 15, 29, and 42.
All Cause Mortality
	Treatment (Panitumumab, Chemotherapy, Radiation)
	Affected / at Risk (%)	# Events
Total	7/11 (63.6%)
Serious Adverse Events
	Treatment (Panitumumab, Chemotherapy, Radiation)
	Affected / at Risk (%)	# Events
Total	10/11 (90.9%)
Blood and lymphatic system disorders
Anemia	1/11 (9.1%)	4
Febrile Neutropenia	1/11 (9.1%)	1
Cardiac disorders
bradycardia	1/11 (9.1%)	1
Pericarditis	1/11 (9.1%)	1
Chest pain - cardiac	1/11 (9.1%)	1
Gastrointestinal disorders
diarrhea	1/11 (9.1%)	1
nausea	1/11 (9.1%)	1
Vomiting	1/11 (9.1%)	1
Gastrointestinal disorders - Other	2/11 (18.2%)	2
Gastrointestinal disorders - Other	1/11 (9.1%)	1
Gastrointestinal disorders - Other	1/11 (9.1%)	1
Gastrointestinal disorders - Other	1/11 (9.1%)	1
Small intestinal obstruction	1/11 (9.1%)	2
Malabsorption	1/11 (9.1%)	1
Abdominal pain	1/11 (9.1%)	1
Gastrointestinal disorders - Other	1/11 (9.1%)	1
Typhlitis	1/11 (9.1%)	1
Ileus	1/11 (9.1%)	1
General disorders
Fatigue	1/11 (9.1%)	1
Non-cardiac chest pain	1/11 (9.1%)	1
Fever	2/11 (18.2%)	2
General disorders - Other	1/11 (9.1%)	1
pain	1/11 (9.1%)	1
Infections and infestations
Lung infection	3/11 (27.3%)	5
Sepsis	2/11 (18.2%)	2
Infections and infestations - Other	1/11 (9.1%)	1
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications - Other	1/11 (9.1%)	1
Investigations
Weight loss	1/11 (9.1%)	1
Troponin increase	1/11 (9.1%)	1
lymphocyte count decreased	1/11 (9.1%)	1
Investigations - Other	1/11 (9.1%)	2
Metabolism and nutrition disorders
dehydration	2/11 (18.2%)	3
Anorexia	1/11 (9.1%)	1
Hyponatremia	1/11 (9.1%)	1
alcohol intolerance	1/11 (9.1%)	1
Acidosis	1/11 (9.1%)	1
Alkalosis	1/11 (9.1%)	2
Nervous system disorders
Depressed level of consciousness	1/11 (9.1%)	1
Dizziness	1/11 (9.1%)	1
Psychiatric disorders
suicidal ideation	1/11 (9.1%)	1
hallucinations	1/11 (9.1%)	1
depression	1/11 (9.1%)	1
Renal and urinary disorders
Hematuria	1/11 (9.1%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia	3/11 (27.3%)	6
Adult respiratory distress syndrome	3/11 (27.3%)	3
pulmonary edema	1/11 (9.1%)	1
Respiratory failure	2/11 (18.2%)	3
Dyspnea	3/11 (27.3%)	3
Aspiration	1/11 (9.1%)	1
Hoarseness	1/11 (9.1%)	1
Surgical and medical procedures
Surgical and medical procedures - Other	2/11 (18.2%)	2
Vascular disorders
Thromboembolic event	2/11 (18.2%)	2
Thromboembolic event	1/11 (9.1%)	1
hypotension	3/11 (27.3%)	4
Other (Not Including Serious) Adverse Events
	Treatment (Panitumumab, Chemotherapy, Radiation)
	Affected / at Risk (%)	# Events
Total	11/11 (100%)
Blood and lymphatic system disorders
Anemia	7/11 (63.6%)	27
Febrile neutropenia	1/11 (9.1%)	1
Gastrointestinal disorders
Diarrhea	2/11 (18.2%)	2
dysphagia	4/11 (36.4%)	5
mucositis - oral	1/11 (9.1%)	1
constipation	1/11 (9.1%)	1
Nausea	2/11 (18.2%)	2
Ileus	1/11 (9.1%)	1
Injury, poisoning and procedural complications - Other	1/11 (9.1%)	1
Esophageal pain	1/11 (9.1%)	1
Abdominal pain	1/11 (9.1%)	1
General disorders
Pain	2/11 (18.2%)	3
Fatigue	1/11 (9.1%)	2
Infections and infestations
Lung infection	2/11 (18.2%)	2
Infections and infestations - Other	1/11 (9.1%)	1
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications - Other	1/11 (9.1%)	1
Injury, poisoning and procedural complications - Other	1/11 (9.1%)	2
Investigations
lymphocyte count decreased	7/11 (63.6%)	36
White blood cells decreased	8/11 (72.7%)	18
Neutrophil count decreased	7/11 (63.6%)	13
Platelet cell count decreased	2/11 (18.2%)	5
blood bilirubin increased	1/11 (9.1%)	1
INR increased	1/11 (9.1%)	1
Aspartate aminotransferase increased	1/11 (9.1%)	2
Alanine aminotransferase	1/11 (9.1%)	2
weight loss	2/11 (18.2%)	2
Electrocardiogram QT corrected interval prolonged	1/11 (9.1%)	1
Alkaline phosphatase increased	1/11 (9.1%)	1
Metabolism and nutrition disorders
Anorexia	8/11 (72.7%)	10
Hypokalemia	9/11 (81.8%)	19
hyperglycemia	3/11 (27.3%)	3
Acidosis	1/11 (9.1%)	3
Hypoalbuminemia	4/11 (36.4%)	6
hypophosphatemia	4/11 (36.4%)	5
hypocalcemia	2/11 (18.2%)	2
hyponatremia	1/11 (9.1%)	2
Alkalosis	1/11 (9.1%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	2/11 (18.2%)	2
Nervous system disorders
dysgeusia	1/11 (9.1%)	1
Depressed level of consciousness	1/11 (9.1%)	1
Psychiatric disorders
depression	1/11 (9.1%)	1
Respiratory, thoracic and mediastinal disorders
Hoarseness	2/11 (18.2%)	2
pleural effusion	1/11 (9.1%)	1
Respiratory failure	1/11 (9.1%)	1
Respiratory, thoracic and mediastinal disorders - Other	1/11 (9.1%)	1
hypoxia	3/11 (27.3%)	6
Adult respiratory distress syndrome	1/11 (9.1%)	1
Dyspnea	1/11 (9.1%)	1
Skin and subcutaneous tissue disorders
Skin and subcutatneous tissue disorder - Other	1/11 (9.1%)	1
Vascular disorders
Hypotension	2/11 (18.2%)	2
thromboembolic event	1/11 (9.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.