Radiation Therapy, Pemetrexed Disodium, and Carboplatin in Treating Patients With Locally Advanced Esophageal Cancer That Can Be Removed By Surgery

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00268437
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 27
• Locations: 90
• Arm: 1
• Duration (Months): 107
• Patients Per Site: 0.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as pemetrexed disodium and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pemetrexed disodium may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving radiation therapy together with pemetrexed disodium and carboplatin before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying how well giving radiation therapy together with pemetrexed disodium and carboplatin works in treating patients with locally advanced esophageal cancer that can be removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Cancer	Drug: carboplatin; Drug: Pemetrexed; Procedure: conventional surgery; Procedure: neoadjuvant therapy; Radiation: radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the pathologic complete response rate of radiotherapy, pemetrexed disodium, and carboplatin when administered prior to esophagectomy in patients with locally advanced esophageal cancer.

Secondary

• Determine the activity, in terms of clinical response rate and adverse event profile of radiotherapy, pemetrexed disodium, and carboplatin when administered prior to esophagectomy.

• Determine the overall survival, time-to-progression, and time-to-treatment failure for patients receiving the above combined modality treatment.

• Determine the surgical outcome for all patients who undergo esophagectomy.

• Determine the time-to-disease recurrence and disease-free survival for patients who have a curative resection.

• Determine quality of life of patients treated with this regimen. OUTLINE: This is a multicenter study. Patients undergo radiotherapy once daily, 5 days a week, for 5 ½ weeks and concurrently receive pemetrexed disodium IV over 10 minutes and carboplatin IV over 30 minutes on days 1 and 22. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients who are eligible will undergo esophagectomy between 4-12 weeks after completion of radiotherapy.

Quality of life is assessed at baseline, immediately prior to day 22 of chemotherapy, and within 2 weeks prior to surgery.

After completion of study treatment, patients are followed periodically for approximately 4 years.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Preoperative Radiation and Chemotherapy (Pemetrexed and Carboplatin) for Locally Advanced Esophageal Cancer
• Study Start Date: Apr 1, 2006
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Pemetrexed/Carboplatin Pemetrexed+Carboplatin+Radiation

Drug: carboplatin; carboplatin is to be given on days 1 and 22 of the 5 ½ weeks of radiation treatment.; Drug: Pemetrexed; Pemetrexed is to be given on days 1 and 22 of the 5 ½ weeks of radiation treatment.; Procedure: conventional surgery; Procedure: neoadjuvant therapy; Radiation: radiation therapy; Radiation therapy begins day 1 and continues for 5 ½ weeks (45 Gy in 22-25 fractions of 1.8 Gy to extended field; 50.4 Gy in 28 fractions within boost field).

Outcome Measures

Primary Outcome Measures

1. Pathologic Complete Response Rate [Baseline to time of surgery (around 10 - 18 weeks post-baseline)]

   The proportion of pathologic complete responses will be estimated by the number of pathologic complete responses divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true pathologic complete response rate will be calculated. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for Measurable disease is defined as at least one lesion whose longest diameter can be accurately measured as ≥2.0 cm with conventional techniques or as ≥1.0 cm with spiral CT. Lesions on chest x-ray are acceptable as measurable lesions when they are clearly defined and surrounded by aerated lung. However, CT is preferable.

Secondary Outcome Measures

1. Overall Survival [From baseline to 4 years]

   Time from registration to death due to any cause.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal (GE) junction

• No T1-2, N0, M0 disease

• No palpable or biopsy-proven involvement of supraclavicular nodes or radiographically involved supraclavicular nodes (> 1.5 cm in greatest dimension) for lesions in mid-thoracic, distal thoracic, or GE junction

• Supraclavicular node involvement allowed provided there are upper thoracic esophagus primary lesions

• Patients with involvement of celiac nodes (stations 15-20) are eligible if the primary lesion is mid-thoracic, distal esophagus, or GE junction

• No evidence of distant metastases

• Tumor must be considered surgically resectable

• Patients with T4, N0 tumors that are potentially resectable are eligible

• No clinically relevant pleural or peritoneal effusion that is not amenable to drainage

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Life expectancy ≥ 12 weeks

• Absolute neutrophil count ≥1,500/mm^3

• Platelet count ≥100,000/mm^3

• Hemoglobin ≥10 g/dL

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

• AST ≤ 3 times ULN

• Creatinine clearance ≥ 45 mL/min

• No New York Heart Association class III or IV congestive heart failure

• Pregnant or nursing women are ineligible

• Negative pregnancy test

• Fertile patients must use effective contraception

• No uncontrolled infection

• No other severe underlying disease that would preclude study entry

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ

• No prior sensitivity or allergic reaction to pemetrexed disodium or carboplatin

• Able to swallow pills

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy for esophageal cancer

• No prior radiotherapy field that overlapped the anticipated fields of study radiotherapy

• No prior radiotherapy to > 30% of the marrow cavity

• Patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) must be able to discontinue use 2 days prior, during, and 2 days after pemetrexed disodium administration (5 days prior for long-life NSAIDs)

• Patients must not have been receiving cyclooxygenase-2 inhibitors at study entry and while receiving protocol therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
2	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224
3	Rush-Copley Cancer Care Center	Aurora	Illinois	United States	60507
4	Graham Hospital	Canton	Illinois	United States	61520
5	Memorial Hospital	Carthage	Illinois	United States	62321
6	St. Anthony's Memorial Hospital	Effingham	Illinois	United States	62401
7	Eureka Community Hospital	Eureka	Illinois	United States	61530
8	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
9	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
10	InterCommunity Cancer Center of Western Illinois	Galesburg	Illinois	United States	61401
11	Mason District Hospital	Havana	Illinois	United States	62644
12	Hopedale Medical Complex	Hopedale	Illinois	United States	61747
13	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois	United States	60435
14	Kewanee Hospital	Kewanee	Illinois	United States	61443
15	McDonough District Hospital	Macomb	Illinois	United States	61455
16	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
17	Community Cancer Center	Normal	Illinois	United States	61761
18	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
19	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
20	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
21	Proctor Hospital	Peoria	Illinois	United States	61614
22	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
23	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
24	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
25	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
26	Perry Memorial Hospital	Princeton	Illinois	United States	61356
27	St. Margaret's Hospital	Spring Valley	Illinois	United States	61362
28	Valley Cancer Center	Spring Valley	Illinois	United States	61362
29	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois	United States	61801
30	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
31	Saint Anthony Memorial Health Centers	Michigan City	Indiana	United States	46360
32	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa	United States	52403
33	Mercy Capitol Hospital	Des Moines	Iowa	United States	50307
34	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
35	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
36	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa	United States	50309
37	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa	United States	50314
38	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
39	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
40	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
41	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51104
42	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
43	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
44	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
45	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
46	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
47	Hurley Medical Center	Flint	Michigan	United States	48503
48	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
49	Foote Hospital	Jackson	Michigan	United States	49201
50	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
51	Seton Cancer Institute - Saginaw	Saginaw	Michigan	United States	48601
52	St. John Macomb Hospital	Warren	Michigan	United States	48093
53	Albert Lea Cancer Center at Albert Lea Medical Center	Albert Lea	Minnesota	United States	56007
54	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
55	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
56	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota	United States	55805-1983
57	CCOP - Duluth	Duluth	Minnesota	United States	55805
58	Miller - Dwan Medical Center	Duluth	Minnesota	United States	55805
59	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
60	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
61	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
62	Meeker County Memorial Hospital	Lichfield	Minnesota	United States	55355
63	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota	United States	55109
64	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
65	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
66	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
67	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
68	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
69	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
70	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
71	HealthEast Cancer Care at St. Joseph's Hospital	St Paul	Minnesota	United States	55102
72	Park Nicollet Cancer Center	St. Louis Park	Minnesota	United States	55416
73	Regions Hospital Cancer Care Center	St. Paul	Minnesota	United States	55101
74	United Hospital	St. Paul	Minnesota	United States	55102
75	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
76	HealthEast Cancer Care at Woodwinds Health Campus	Woodbury	Minnesota	United States	55125
77	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
78	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
79	Bismarck Cancer Center	Bismarck	North Dakota	United States	58501
80	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota	United States	58501
81	Mid Dakota Clinic, PC	Bismarck	North Dakota	United States	58501
82	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota	United States	58502
83	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
84	AnMed Cancer Center	Anderson	South Carolina	United States	29621
85	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
86	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
87	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
88	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
89	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
90	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039

Sponsors and Collaborators

• Alliance for Clinical Trials in Oncology
• National Cancer Institute (NCI)

Investigators

• Study Chair: Aminah Jatoi, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00268437
• Other Study ID Numbers: NCCTG-N044E; NCI-2012-02678; CDR0000455635
• First Posted: Dec 22, 2005
• Last Update Posted: Jul 6, 2016
• Last Verified: Jul 1, 2016

• Keywords provided by Alliance for Clinical Trials in Oncology: adenocarcinoma of the esophagus; squamous cell carcinoma of the esophagus; stage III esophageal cancer; stage II esophageal cancer
• Additional relevant MeSH terms: Esophageal Neoplasms; Carboplatin; Pemetrexed

Study Results

Participant Flow

Recruitment Details	This trial closed early because, during an interim analysis, the primary endpoint fell short. However, 26 eligible patients were accrued. Due to early closure not all the endpoints were analyzed.

Arm/Group Title	Pemetrexed/Carboplatin
Arm/Group Description	Pemetrexed+Carboplatin+Radiation carboplatin: carboplatin is to be given on days 1 and 22 of the 5 ½ weeks of radiation treatment. Pemetrexed: Pemetrexed is to be given on days 1 and 22 of the 5 ½ weeks of radiation treatment. Radiation therapy: Radiation therapy begins day 1 and continues for 5 ½ weeks (45 Gy in 22-25 fractions of 1.8 Gy to extended field; 50.4 Gy in 28 fractions within boost field). Conventional surgery
Period Title: Overall Study
STARTED	27
COMPLETED	26
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Pemetrexed/Carboplatin
Arm/Group Description	Pemetrexed+Carboplatin+Radiation> > carboplatin: carboplatin is to be given on days 1 and 22 of the 5 ½ weeks of radiation treatment.> > Pemetrexed: Pemetrexed is to be given on days 1 and 22 of the 5 ½ weeks of radiation treatment.> > conventional surgery> > neoadjuvant therapy> > radiation therapy: Radiation therapy begins day 1 and continues for 5 ½ weeks (45 Gy in 22-25 fractions of 1.8 Gy to extended field; 50.4 Gy in 28 fractions within boost field).
Overall Participants	27
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	66
Sex: Female, Male (Count of Participants)
Female	7 25.9%
Male	20 74.1%
Region of Enrollment (participants) [Number]
United States	27 100%

Outcome Measures

1. Primary Outcome

Title	Pathologic Complete Response Rate
Description	The proportion of pathologic complete responses will be estimated by the number of pathologic complete responses divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true pathologic complete response rate will be calculated. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for Measurable disease is defined as at least one lesion whose longest diameter can be accurately measured as ≥2.0 cm with conventional techniques or as ≥1.0 cm with spiral CT. Lesions on chest x-ray are acceptable as measurable lesions when they are clearly defined and surrounded by aerated lung. However, CT is preferable.
Time Frame	Baseline to time of surgery (around 10 - 18 weeks post-baseline)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pemetrexed/Carboplatin
Arm/Group Description	Pemetrexed+Carboplatin+Radiation carboplatin: carboplatin is to be given on days 1 and 22 of the 5 ½ weeks of radiation treatment. Pemetrexed: Pemetrexed is to be given on days 1 and 22 of the 5 ½ weeks of radiation treatment. Radiation therapy: Radiation therapy begins day 1 and continues for 5 ½ weeks (45 Gy in 22-25 fractions of 1.8 Gy to extended field; 50.4 Gy in 28 fractions within boost field). conventional surgery
Measure Participants	26
Number (95% Confidence Interval) [percentage of participants]	23 85.2%

2. Secondary Outcome

Title	Overall Survival
Description	Time from registration to death due to any cause.
Time Frame	From baseline to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pemetrexed/Carboplatin
Arm/Group Description	Pemetrexed+Carboplatin+Radiation carboplatin: carboplatin is to be given on days 1 and 22 of the 5 ½ weeks of radiation treatment. Pemetrexed: Pemetrexed is to be given on days 1 and 22 of the 5 ½ weeks of radiation treatment. Radiation therapy: Radiation therapy begins day 1 and continues for 5 ½ weeks (45 Gy in 22-25 fractions of 1.8 Gy to extended field; 50.4 Gy in 28 fractions within boost field). Conventional surgery
Measure Participants	26
Median (95% Confidence Interval) [months]	17.8

Adverse Events

Arm/Group Title	Pemetrexed/Carboplatin
Arm/Group Description	Pemetrexed+Carboplatin+Radiation carboplatin: carboplatin is to be given on days 1 and 22 of the 5 ½ weeks of radiation treatment. Pemetrexed: Pemetrexed is to be given on days 1 and 22 of the 5 ½ weeks of radiation treatment. Radiation therapy: Radiation therapy begins day 1 and continues for 5 ½ weeks (45 Gy in 22-25 fractions of 1.8 Gy to extended field; 50.4 Gy in 28 fractions within boost field). Conventional surgery
All Cause Mortality
	Pemetrexed/Carboplatin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Pemetrexed/Carboplatin
	Affected / at Risk (%)	# Events
Total	6/27 (22.2%)
Blood and lymphatic system disorders
Hemoglobin decreased	1/27 (3.7%)	1
Cardiac disorders
Atrial fibrillation	1/27 (3.7%)	1
Gastrointestinal disorders
Dysphagia	1/27 (3.7%)	1
Esophageal fistula	1/27 (3.7%)	1
Nausea	1/27 (3.7%)	1
Small intestinal obstruction	1/27 (3.7%)	1
Vomiting	1/27 (3.7%)	1
Infections and infestations
Sepsis	1/27 (3.7%)	1
Investigations
Leukocyte count decreased	1/27 (3.7%)	1
Neutrophil count decreased	1/27 (3.7%)	1
Platelet count decreased	1/27 (3.7%)	1
Metabolism and nutrition disorders
Serum phosphate decreased	1/27 (3.7%)	1
Serum potassium decreased	1/27 (3.7%)	1
Renal and urinary disorders
Renal failure	1/27 (3.7%)	1
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	1/27 (3.7%)	1
Dyspnea	1/27 (3.7%)	1
Pneumonitis	1/27 (3.7%)	1
Other (Not Including Serious) Adverse Events
	Pemetrexed/Carboplatin
	Affected / at Risk (%)	# Events
Total	27/27 (100%)
Blood and lymphatic system disorders
Hemoglobin decreased	25/27 (92.6%)	59
Cardiac disorders
Atrial fibrillation	2/27 (7.4%)	2
Myocardial ischemia	1/27 (3.7%)	1
Pericardial effusion	1/27 (3.7%)	1
Pericarditis	1/27 (3.7%)	1
Gastrointestinal disorders
Constipation	3/27 (11.1%)	4
Diarrhea	11/27 (40.7%)	15
Dysphagia	20/27 (74.1%)	48
Esophageal mucositis	7/27 (25.9%)	10
Esophageal pain	11/27 (40.7%)	21
Esophagitis	16/27 (59.3%)	30
Nausea	19/27 (70.4%)	36
Oesophagoscopy abnormal	7/27 (25.9%)	9
Vomiting	9/27 (33.3%)	12
General disorders
Death NOS	1/27 (3.7%)	1
Edema limbs	1/27 (3.7%)	1
Fatigue	8/27 (29.6%)	12
Infections and infestations
Endocarditis infective	1/27 (3.7%)	1
Pharyngitis	1/27 (3.7%)	1
Pleural infection	2/27 (7.4%)	2
Pneumonia	2/27 (7.4%)	2
Small intestine infection	1/27 (3.7%)	1
Soft tissue infection	1/27 (3.7%)	1
Upper respiratory infection	1/27 (3.7%)	1
Urinary tract infection	1/27 (3.7%)	1
Wound infection	1/27 (3.7%)	1
Injury, poisoning and procedural complications
Esophageal anastomotic leak	1/27 (3.7%)	1
Vascular access complication	1/27 (3.7%)	1
Investigations
Alkaline phosphatase increased	1/27 (3.7%)	2
Aspartate aminotransferase increased	8/27 (29.6%)	9
Blood bilirubin increased	1/27 (3.7%)	1
Leukocyte count decreased	24/27 (88.9%)	43
Lymphocyte count decreased	1/27 (3.7%)	2
Neutrophil count decreased	23/27 (85.2%)	37
Platelet count decreased	23/27 (85.2%)	47
Weight loss	2/27 (7.4%)	5
Metabolism and nutrition disorders
Anorexia	4/27 (14.8%)	8
Blood glucose increased	1/27 (3.7%)	1
Dehydration	2/27 (7.4%)	3
Serum albumin decreased	1/27 (3.7%)	1
Serum glucose decreased	1/27 (3.7%)	1
Serum phosphate decreased	1/27 (3.7%)	1
Serum potassium decreased	1/27 (3.7%)	1
Musculoskeletal and connective tissue disorders
Chest wall pain	1/27 (3.7%)	1
Muscle weakness	1/27 (3.7%)	1
Neck pain	1/27 (3.7%)	2
Nervous system disorders
Dysgeusia	1/27 (3.7%)	1
Headache	1/27 (3.7%)	1
Peripheral sensory neuropathy	3/27 (11.1%)	8
Psychiatric disorders
Depression	5/27 (18.5%)	5
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	2/27 (7.4%)	2
Aspiration	1/27 (3.7%)	1
Atelectasis	1/27 (3.7%)	1
Cough	1/27 (3.7%)	1
Dyspnea	8/27 (29.6%)	14
Hiccups	1/27 (3.7%)	1
Hypoxia	2/27 (7.4%)	3
Pleural effusion	3/27 (11.1%)	3
Pneumonitis	1/27 (3.7%)	1
Pneumothorax	2/27 (7.4%)	2
Skin and subcutaneous tissue disorders
Decubitus ulcer	1/27 (3.7%)	1
Erythema multiforme	1/27 (3.7%)	1
Rash acneiform	1/27 (3.7%)	1
Rash desquamating	10/27 (37%)	12
Vascular disorders
Hypotension	7/27 (25.9%)	10
Thrombosis	2/27 (7.4%)	2

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.