Cisplatin, Irinotecan, and Radiation Therapy in Treating Patients With Esophageal Cancer or Gastroesophageal Junction Cancer That Can Be Removed By Surgery

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT00316862
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 82
• Locations: 24
• Arm: 1
• Actual Duration (Months): 104.4
• Patients Per Site: 3.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial studies how well giving cisplatin and irinotecan hydrochloride together with radiation therapy works in treating patients with esophageal cancer or gastroesophageal junction cancer that can be removed by surgery. Drugs used in chemotherapy, such as cisplatin and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with 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
Esophageal Cancer	Drug: cisplatin; Drug: irinotecan hydrochloride; Procedure: therapeutic conventional surgery; Radiation: radiation therapy	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the pathologic complete response rate in patients with surgically resectable esophageal cancer treated pre-operatively with induction chemotherapy with weekly cisplatin and irinotecan (irinotecan hydrochloride) followed by concurrent cisplatin/irinotecan and radiation therapy.

SECONDARY OBJECTIVES:

1. To evaluate potential response or progression of disease during induction chemotherapy with positron emission tomography (PET) scan.

2. To evaluate the toxicity and tolerability of therapy, including surgical morbidity and mortality.

3. To determine the overall survival, disease free survival, and pattern of failure.

OUTLINE:

INDUCTION CHEMOTHERAPY (COURSES 1-2): Patients receive cisplatin intravenously (IV) over 30 minutes and irinotecan hydrochloride IV over 30-90 minutes on days 1 and 8 of courses 1 and 2. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

CHEMORADIOTHERAPY (COURSES 3-4): Beginning 2 weeks after completion of induction chemotherapy, patients receive cisplatin and irinotecan hydrochloride as in induction chemotherapy on days 1 and 8 of courses 3 and 4 and undergo radiotherapy daily 5 days a week in course 3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

SURGERY: Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo surgery to remove the tumor.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 82 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Preoperative Irinotecan, Cisplatin and Radiation in Esophageal Cancer
• Actual Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Oct 15, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (chemotherapy, chemoradiotherapy, surgery) INDUCTION CHEMOTHERAPY (COURSES 1-2): Patients receive cisplatin intravenously (IV) over 30 minutes and irinotecan hydrochloride IV over 30-90 minutes on days 1 and 8 of courses 1 and 2. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. CHEMORADIOTHERAPY (COURSES 3-4): Beginning 2 weeks after completion of induction chemotherapy, patients receive cisplatin and irinotecan hydrochloride as in induction chemotherapy on days 1 and 8 of courses 3 and 4 and undergo radiotherapy daily 5 days a week in course 3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. SURGERY: Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo surgery to remove the tumor.

Drug: cisplatin; Given IV; Drug: irinotecan hydrochloride; Given IV; Procedure: therapeutic conventional surgery; Undergo Surgery; Radiation: radiation therapy; Undergo radiation; Other Names: irradiation, radiotherapy, therapy, radiation

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients With Adenocarcinoma Achieving a Pathologic Complete Response (CR) After Surgery [Up to 5 years]

   A pathological complete response is defined as no tumor found on pathology review at surgery in all resected lymph nodes and tissue. All tissues sampled must have NO viable tumor

Secondary Outcome Measures

1. Utility of Early PET Imaging in Predicting Response to Treatment [Up to 55 days]

2. Disease-free Survival [Up to 5 years]

3. Overall Survival [Up to 5 years]

4. Patterns of Failure [Up to 5 years]

5. Proportion of Patients Experiencing Grade 3 or Greater Pneumonitis or Esophagitis [Up to 5 years]

   Proportion of patients experiencing grade 3 or greater pneumonitis or esophagitis, deemed at least possibly related to treatment graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

6. Proportion of Patients Experiencing Grade 3 or Greater Hematologic and Non-hematologic Toxicity [Up to 5 years]

   Proportion of patients experiencing grade 3 or greater hematologic and non-hematologic toxicity, deemed as at least possibly related to treatment, graded using the NCI CTCAE version 3.0

Eligibility Criteria

Criteria

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

• Histologically or cytologically confirmed adenocarcinoma, poorly differentiated carcinoma, or carcinoma not otherwise specified, of the esophagus or gastroesophageal junction; biopsy or cytology of the primary tumor, or of involved regional lymph nodes, is acceptable

• Tumors must be TNM stage T2-4, N0-1, M0 as determined by pretreatment endoscopic ultrasound; T1 tumors are eligible if they are T1, N1, M0; regional thoracic lymph node involvement (N1) is permitted

• Disease must be clinically limited to the esophagus or gastroesophageal junction; if the tumor extends below the gastroesophageal junction into the proximal stomach, 50% of the tumor must involve the distal esophagus or gastroesophageal junction; adenocarcinomas of the distal esophagus would therefore include tumors of the distal esophagus, or Siewert type I according to the Siewert classification, and tumors of the gastroesophageal junction which involve equally both the distal esophagus and proximal stomach, or Siewert type II; tumor must be surgically resectable

• No TIS (in-situ carcinoma) and tumors determined to be T1N0 following endoscopic ultrasound

• No clinical involvement on endoscopic ultrasound (EUS), computed tomography (CT) scan, or PET scan of supraclavicular or celiac lymph node involvement (stage IVa, T any N any M1a) unless this is proven to be a false positive by an appropriate biopsy

• No patients with cervical esophageal tumors, or gastric cancers with minor involvement of the gastroesophageal junction or distal esophagus

• No patients with tracheoesophageal fistulas

• Patients with evidence of metastatic disease are not eligible; this includes:

• Positive malignant cytology of the pleura, pericardium or peritoneum

• Radiographic evidence of distance organ involvement including lung, liver, bone, or brain

• No prior chemotherapy or radiotherapy is permitted; patients must be at least 4 weeks since major surgery, or must have recovered from the effects of minor surgery (laparoscopy, thoracoscopy)

• No prior malignancies (other than basal cell/squamous carcinoma of the skin, in-situ cervical carcinoma, or superficial transitional cell bladder carcinoma) are permitted unless diagnosed and/or treated >= 3 years before registration and without evidence of recurrence

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

• No evidence of recurrent laryngeal nerve or phrenic nerve paralysis

• No known Gilbert's disease

• No clinically significant hearing loss; audiograms should be done in patients in which they are clinically indicated

• No history of active seizure disorder; no ongoing treatment with phenytoin, phenobarbital, or other antiepileptic medication; patients who are receiving valproic acid are eligible

• No New York Heart Association class III or IV heart disease; no angina or myocardial infarction within the last 6 months

Inclusion Criteria:

• No history of clinically significant ventricular arrhythmia requiring ongoing medication with antiarrhythmics

• Absolute neutrophil count (ANC) >= 1,500/ul

• Platelet count >= 100,000/ul

• Hemoglobin >= 9 gm/dl

• Serum creatinine =< upper limit of normal (ULN)

• Total serum bilirubin =< 1.5 mg/dl

• Forced expiratory volume in 1 second (FEV-1) >= 1.2 liters OR >= 35% of normal as a value that is indexed to body size

• Pulmonary function tests (PFT) >= 1.2 liters OR >= 35% of normal as a value that is indexed to body size

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Elkhart General Hospital	Elkhart	Indiana	United States	46515
2	Howard Community Hospital	Kokomo	Indiana	United States	46904
3	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
4	Saint Joseph Regional Medical Center	Mishawaka	Indiana	United States	46545-1470
5	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
6	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
7	Michiana Hematology-Oncology, PC - South Bend	South Bend	Indiana	United States	46601
8	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa	United States	52242-1002
9	CancerCare of Maine at Eastern Maine Medical Center	Bangor	Maine	United States	04401
10	Maine Center for Cancer Medicine and Blood Disorders - Scarborough	Scarborough	Maine	United States	04074
11	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan	United States	49085
12	Methodist Estabrook Cancer Center	Omaha	Nebraska	United States	68114
13	New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care	Concord	New Hampshire	United States	03301
14	New Hampshire Oncology - Hematology, PA - Hooksett	Hooksett	New Hampshire	United States	03106
15	Lakes Region General Hospital	Laconia	New Hampshire	United States	03246
16	Elliot Regional Cancer Center at Elliot Hospital	Manchester	New Hampshire	United States	03103
17	Veterans Affairs Medical Center - Buffalo	Buffalo	New York	United States	14215
18	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
19	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
20	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
21	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
22	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210-1240
23	Mountainview Medical	Berlin	Vermont	United States	05602
24	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont	United States	05401

Sponsors and Collaborators

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

Investigators

• Study Chair: David H. Ilson, MD, PhD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00316862
• Other Study ID Numbers: CALGB-80302; CDR0000468495; NCI-2009-00491; U10CA180821
• First Posted: Apr 21, 2006
• Last Update Posted: May 8, 2018
• Last Verified: Apr 1, 2018

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

Study Results

Participant Flow

Recruitment Details	Between February 2006 and August 2011, 82 participants were recruited to this study.

Arm/Group Title	Treatment (Chemotherapy, Chemoradiotherapy, Surgery)
Arm/Group Description	INDUCTION CHEMOTHERAPY (COURSES 1-2): Patients receive cisplatin 30 mg/m^2 intravenously (IV) over 30 minutes and irinotecan hydrochloride 65 mg/m^2 IV over 30-90 minutes on days 1 and 8 of courses 1 and 2. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. CHEMORADIOTHERAPY (COURSES 3-4): Beginning 2 weeks after completion of induction chemotherapy, patients receive cisplatin and irinotecan hydrochloride as in induction chemotherapy on days 1 and 8 of courses 3 and 4 and undergo radiotherapy daily 5 days a week in course 3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. SURGERY: Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo surgery to remove the tumor.
Period Title: Overall Study
STARTED	82
COMPLETED	82
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Chemotherapy, Chemoradiotherapy, Surgery)
Arm/Group Description	INDUCTION CHEMOTHERAPY (COURSES 1-2): Patients receive cisplatin 30 mg/m^2 intravenously (IV) over 30 minutes and irinotecan hydrochloride 65 mg/m^2 IV over 30-90 minutes on days 1 and 8 of courses 1 and 2. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. CHEMORADIOTHERAPY (COURSES 3-4): Beginning 2 weeks after completion of induction chemotherapy, patients receive cisplatin and irinotecan hydrochloride as in induction chemotherapy on days 1 and 8 of courses 3 and 4 and undergo radiotherapy daily 5 days a week in course 3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. SURGERY: Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo surgery to remove the tumor.
Overall Participants	82
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62.2
Sex: Female, Male (Count of Participants)
Female	13 15.9%
Male	69 84.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	77 93.9%
Unknown or Not Reported	5 6.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 2.4%
White	77 93.9%
More than one race	2 2.4%
Unknown or Not Reported	1 1.2%
Region of Enrollment (participants) [Number]
United States	82 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients With Adenocarcinoma Achieving a Pathologic Complete Response (CR) After Surgery
Description	A pathological complete response is defined as no tumor found on pathology review at surgery in all resected lymph nodes and tissue. All tissues sampled must have NO viable tumor
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

27 participants with adenocarcinoma were recruited and evaluated for the primary outcome per protocol design.

Arm/Group Title	Treatment (Chemotherapy, Chemoradiotherapy, Surgery)
Arm/Group Description	INDUCTION CHEMOTHERAPY (COURSES 1-2): Patients receive cisplatin 30 mg/m^2 intravenously (IV) over 30 minutes and irinotecan hydrochloride 65 mg/m^2 IV over 30-90 minutes on days 1 and 8 of courses 1 and 2. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. CHEMORADIOTHERAPY (COURSES 3-4): Beginning 2 weeks after completion of induction chemotherapy, patients receive cisplatin and irinotecan hydrochloride as in induction chemotherapy on days 1 and 8 of courses 3 and 4 and undergo radiotherapy daily 5 days a week in course 3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. SURGERY: Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo surgery to remove the tumor.
Measure Participants	27
Number (95% Confidence Interval) [percentage of participants]	19 23.2%

2. Secondary Outcome

Title	Utility of Early PET Imaging in Predicting Response to Treatment
Time Frame	Up to 55 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Disease-free Survival
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Overall Survival
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Patterns of Failure
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Proportion of Patients Experiencing Grade 3 or Greater Pneumonitis or Esophagitis
Description	Proportion of patients experiencing grade 3 or greater pneumonitis or esophagitis, deemed at least possibly related to treatment graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

1 participant was not evaluated for adverse events.

Arm/Group Title	Treatment (Chemotherapy, Chemoradiotherapy, Surgery)
Arm/Group Description	INDUCTION CHEMOTHERAPY (COURSES 1-2): Patients receive cisplatin 30 mg/m^2 intravenously (IV) over 30 minutes and irinotecan hydrochloride 65 mg/m^2 IV over 30-90 minutes on days 1 and 8 of courses 1 and 2. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. CHEMORADIOTHERAPY (COURSES 3-4): Beginning 2 weeks after completion of induction chemotherapy, patients receive cisplatin and irinotecan hydrochloride as in induction chemotherapy on days 1 and 8 of courses 3 and 4 and undergo radiotherapy daily 5 days a week in course 3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. SURGERY: Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo surgery to remove the tumor.
Measure Participants	81
Pneumonitis	0 0%
Esophagitis	5 6.1%

7. Secondary Outcome

Title	Proportion of Patients Experiencing Grade 3 or Greater Hematologic and Non-hematologic Toxicity
Description	Proportion of patients experiencing grade 3 or greater hematologic and non-hematologic toxicity, deemed as at least possibly related to treatment, graded using the NCI CTCAE version 3.0
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

1 participant was not evaluated for adverse events.

Arm/Group Title	Treatment (Chemotherapy, Chemoradiotherapy, Surgery)
Arm/Group Description	INDUCTION CHEMOTHERAPY (COURSES 1-2): Patients receive cisplatin 30 mg/m^2 intravenously (IV) over 30 minutes and irinotecan hydrochloride 65 mg/m^2 IV over 30-90 minutes on days 1 and 8 of courses 1 and 2. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. CHEMORADIOTHERAPY (COURSES 3-4): Beginning 2 weeks after completion of induction chemotherapy, patients receive cisplatin and irinotecan hydrochloride as in induction chemotherapy on days 1 and 8 of courses 3 and 4 and undergo radiotherapy daily 5 days a week in course 3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. SURGERY: Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo surgery to remove the tumor.
Measure Participants	81
Number [percentage of participants]	72 87.8%

Adverse Events

Arm/Group Title	Treatment (Chemotherapy, Chemoradiotherapy, Surgery)
Arm/Group Description	INDUCTION CHEMOTHERAPY (COURSES 1-2): Patients receive cisplatin 30 mg/m^2 intravenously (IV) over 30 minutes and irinotecan hydrochloride 65 mg/m^2 IV over 30-90 minutes on days 1 and 8 of courses 1 and 2. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. CHEMORADIOTHERAPY (COURSES 3-4): Beginning 2 weeks after completion of induction chemotherapy, patients receive cisplatin and irinotecan hydrochloride as in induction chemotherapy on days 1 and 8 of courses 3 and 4 and undergo radiotherapy daily 5 days a week in course 3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. SURGERY: Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo surgery to remove the tumor.
All Cause Mortality
	Treatment (Chemotherapy, Chemoradiotherapy, Surgery)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Chemotherapy, Chemoradiotherapy, Surgery)
	Affected / at Risk (%)	# Events
Total	6/81 (7.4%)
Blood and lymphatic system disorders
Hemoglobin decreased	5/81 (6.2%)	5
Hemolysis	1/81 (1.2%)	1
Ear and labyrinth disorders
Tinnitus	1/81 (1.2%)	1
Gastrointestinal disorders
Abdominal pain	1/81 (1.2%)	1
Constipation	2/81 (2.5%)	2
Diarrhea	2/81 (2.5%)	2
Dysphagia	3/81 (3.7%)	3
Esophagitis	1/81 (1.2%)	1
Nausea	4/81 (4.9%)	5
Vomiting	3/81 (3.7%)	4
General disorders
Disease progression	1/81 (1.2%)	1
Edema limbs	1/81 (1.2%)	1
Fatigue	4/81 (4.9%)	5
Pain	1/81 (1.2%)	1
Infections and infestations
Infectious colitis	1/81 (1.2%)	1
Injury, poisoning and procedural complications
Radiation recall reaction (dermatologic)	1/81 (1.2%)	1
Investigations
Alkaline phosphatase increased	1/81 (1.2%)	1
Creatinine increased	1/81 (1.2%)	1
Leukocyte count decreased	5/81 (6.2%)	5
Lymphocyte count decreased	1/81 (1.2%)	1
Neutrophil count decreased	4/81 (4.9%)	4
Platelet count decreased	5/81 (6.2%)	6
Weight loss	3/81 (3.7%)	4
Metabolism and nutrition disorders
Anorexia	3/81 (3.7%)	4
Blood glucose increased	4/81 (4.9%)	5
Dehydration	3/81 (3.7%)	3
Serum albumin decreased	2/81 (2.5%)	2
Serum calcium decreased	1/81 (1.2%)	1
Serum magnesium decreased	2/81 (2.5%)	3
Serum potassium decreased	1/81 (1.2%)	2
Serum potassium increased	1/81 (1.2%)	1
Serum sodium decreased	3/81 (3.7%)	4
Nervous system disorders
Dizziness	1/81 (1.2%)	1
Tremor	1/81 (1.2%)	1
Psychiatric disorders
Depression	2/81 (2.5%)	3
Respiratory, thoracic and mediastinal disorders
Cough	1/81 (1.2%)	1
Dyspnea	2/81 (2.5%)	2
Pharyngolaryngeal pain	1/81 (1.2%)	1
Skin and subcutaneous tissue disorders
Alopecia	2/81 (2.5%)	2
Decubitus ulcer	1/81 (1.2%)	1
Dry skin	1/81 (1.2%)	1
Vascular disorders
Thrombosis	2/81 (2.5%)	2
Other (Not Including Serious) Adverse Events
	Treatment (Chemotherapy, Chemoradiotherapy, Surgery)
	Affected / at Risk (%)	# Events
Total	80/81 (98.8%)
Blood and lymphatic system disorders
Febrile neutropenia	4/81 (4.9%)	4
Hemoglobin decreased	71/81 (87.7%)	190
Hemolysis	2/81 (2.5%)	4
Cardiac disorders
Atrial fibrillation	1/81 (1.2%)	1
Cardiac disorder	1/81 (1.2%)	1
Myocardial ischemia	2/81 (2.5%)	3
Palpitations	1/81 (1.2%)	2
Sinus tachycardia	3/81 (3.7%)	3
Ear and labyrinth disorders
Ear disorder	2/81 (2.5%)	5
Hearing impaired	2/81 (2.5%)	3
Tinnitus	9/81 (11.1%)	20
Eye disorders
Dry eye syndrome	2/81 (2.5%)	2
Eye disorder	1/81 (1.2%)	1
Flashing vision	1/81 (1.2%)	2
Vision blurred	3/81 (3.7%)	4
Gastrointestinal disorders
Abdominal pain	14/81 (17.3%)	19
Constipation	36/81 (44.4%)	65
Diarrhea	38/81 (46.9%)	65
Dyspepsia	7/81 (8.6%)	10
Dysphagia	40/81 (49.4%)	87
Ear, nose and throat examination abnormal	1/81 (1.2%)	1
Enteritis	1/81 (1.2%)	1
Esophageal hemorrhage	1/81 (1.2%)	1
Esophageal pain	6/81 (7.4%)	8
Esophageal stenosis	2/81 (2.5%)	3
Esophagitis	13/81 (16%)	15
Flatulence	2/81 (2.5%)	5
Gastritis	1/81 (1.2%)	1
Gastrointestinal disorder	2/81 (2.5%)	2
Gingival pain	1/81 (1.2%)	1
Hemorrhoids	1/81 (1.2%)	3
Mucositis oral	18/81 (22.2%)	26
Nausea	53/81 (65.4%)	106
Oral pain	1/81 (1.2%)	1
Rectal hemorrhage	2/81 (2.5%)	3
Salivary gland disorder	1/81 (1.2%)	2
Small intestinal obstruction	1/81 (1.2%)	1
Small intestinal perforation	1/81 (1.2%)	1
Stomach pain	2/81 (2.5%)	2
Tooth development disorder	1/81 (1.2%)	1
Toothache	1/81 (1.2%)	1
Vomiting	26/81 (32.1%)	38
General disorders
Chest pain	5/81 (6.2%)	5
Chills	2/81 (2.5%)	3
Edema limbs	3/81 (3.7%)	3
Fatigue	60/81 (74.1%)	158
Fever	4/81 (4.9%)	4
Hypothermia	1/81 (1.2%)	1
Pain	7/81 (8.6%)	9
Infections and infestations
Device related infection	1/81 (1.2%)	1
Infective myositis	1/81 (1.2%)	1
Paranasal sinus infection	1/81 (1.2%)	1
Pneumonia	1/81 (1.2%)	1
Skin infection	2/81 (2.5%)	3
Upper respiratory infection	1/81 (1.2%)	1
Wound infection	1/81 (1.2%)	1
Injury, poisoning and procedural complications
Bruising	2/81 (2.5%)	3
Prolonged intubation after pulmonary resection (>24 hrs after surgery)	1/81 (1.2%)	1
Radiation recall reaction (dermatologic)	5/81 (6.2%)	7
Vascular access complication	1/81 (1.2%)	1
Wound dehiscence	1/81 (1.2%)	2
Investigations
Alanine aminotransferase increased	10/81 (12.3%)	16
Alkaline phosphatase increased	10/81 (12.3%)	16
Aspartate aminotransferase increased	6/81 (7.4%)	8
Blood bilirubin increased	3/81 (3.7%)	3
Coagulopathy	1/81 (1.2%)	1
Creatinine increased	5/81 (6.2%)	7
INR increased	1/81 (1.2%)	1
Laboratory test abnormal	1/81 (1.2%)	3
Leukocyte count decreased	70/81 (86.4%)	165
Lymphocyte count decreased	23/81 (28.4%)	44
Neutrophil count decreased	53/81 (65.4%)	112
Platelet count decreased	48/81 (59.3%)	88
Weight gain	2/81 (2.5%)	5
Weight loss	18/81 (22.2%)	27
Metabolism and nutrition disorders
Anorexia	39/81 (48.1%)	67
Blood glucose increased	37/81 (45.7%)	79
Dehydration	27/81 (33.3%)	35
Serum albumin decreased	18/81 (22.2%)	32
Serum calcium decreased	15/81 (18.5%)	23
Serum calcium increased	1/81 (1.2%)	1
Serum glucose decreased	1/81 (1.2%)	1
Serum magnesium decreased	15/81 (18.5%)	24
Serum magnesium increased	3/81 (3.7%)	4
Serum phosphate decreased	1/81 (1.2%)	1
Serum potassium decreased	10/81 (12.3%)	11
Serum potassium increased	4/81 (4.9%)	6
Serum sodium decreased	28/81 (34.6%)	40
Serum sodium increased	5/81 (6.2%)	7
Serum triglycerides increased	1/81 (1.2%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	4/81 (4.9%)	5
Back pain	7/81 (8.6%)	10
Chest wall pain	3/81 (3.7%)	6
Muscle weakness	2/81 (2.5%)	3
Muscle weakness lower limb	1/81 (1.2%)	1
Myalgia	2/81 (2.5%)	2
Neck pain	1/81 (1.2%)	1
Pain in extremity	1/81 (1.2%)	2
Nervous system disorders
Dizziness	10/81 (12.3%)	16
Dysgeusia	7/81 (8.6%)	13
Headache	10/81 (12.3%)	12
Memory impairment	1/81 (1.2%)	1
Neurological disorder NOS	1/81 (1.2%)	1
Peripheral motor neuropathy	2/81 (2.5%)	4
Peripheral sensory neuropathy	21/81 (25.9%)	48
Syncope	3/81 (3.7%)	6
Tremor	1/81 (1.2%)	3
Psychiatric disorders
Anxiety	5/81 (6.2%)	8
Confusion	3/81 (3.7%)	3
Depression	10/81 (12.3%)	15
Euphoria	1/81 (1.2%)	1
Insomnia	19/81 (23.5%)	38
Renal and urinary disorders
Bladder pain	1/81 (1.2%)	1
Proteinuria	2/81 (2.5%)	2
Renal failure	1/81 (1.2%)	1
Urinary frequency	3/81 (3.7%)	6
Urogenital disorder	1/81 (1.2%)	1
Reproductive system and breast disorders
Erectile dysfunction	2/81 (2.5%)	5
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	2/81 (2.5%)	2
Cough	11/81 (13.6%)	17
Dyspnea	18/81 (22.2%)	22
Epistaxis	2/81 (2.5%)	2
Hiccups	4/81 (4.9%)	8
Pharyngolaryngeal pain	7/81 (8.6%)	10
Respiratory disorder	2/81 (2.5%)	2
Skin and subcutaneous tissue disorders
Alopecia	30/81 (37%)	61
Dry skin	7/81 (8.6%)	12
Erythema multiforme	1/81 (1.2%)	4
Pruritus	2/81 (2.5%)	2
Rash acneiform	1/81 (1.2%)	1
Rash desquamating	7/81 (8.6%)	9
Skin disorder	1/81 (1.2%)	1
Skin ulceration	1/81 (1.2%)	1
Sweating	2/81 (2.5%)	2
Vascular disorders
Hemorrhage	1/81 (1.2%)	1
Hot flashes	1/81 (1.2%)	2
Hypertension	2/81 (2.5%)	4
Hypotension	6/81 (7.4%)	6
Phlebitis	1/81 (1.2%)	1
Thrombosis	5/81 (6.2%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.