Bevacizumab, Erlotinib and 5-Fluorouracil With External Beam Radiation Therapy in Locally Advanced Rectal Cancer

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00307736
• Collaborator: Beth Israel Deaconess Medical Center (Other), Dana-Farber Cancer Institute (Other), Genentech, Inc. (Industry)
• Enrollment: 32
• Locations: 3
• Arm: 1
• Duration (Months): 62
• Patients Per Site: 10.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is determine the safety of 5-fluorouracil, bevacizumab and erlotinib when administered in combination with external beam radiation therapy(Phase I portion) as well as to begin to collect information about whether this combination treatment is effective in treating(Phase II portion) patients with locally advanced rectal cancer.

Condition or Disease	Intervention/Treatment	Phase
Rectal Cancer; Adenocarcinoma of the Rectum	Drug: 5-fluorouracil; Drug: bevacizumab; Drug: erlotinib; Procedure: External beam radiation therapy (EBRT)	Phase 1/Phase 2

Detailed Description

• All participants will receive the following drugs: 5-fluorouracil (5-FU) given as a continuous 24-hour infusion; Bevacizumab given intravenously; erlotinib given orally at home. In the Phase I portion, we are looking for the highest dose of erlotinib that can be given safely in combination with the 5-FU, bevacizumab and radiation therapy. Therefore the dose of erlotinib may not be the same for each participant. The dose will increase until we find the highest dose without causing serious or unmanageable side effects.

• Study treatment is given as an outpatient and consists of 14 day cycles with a total of 3 cycles. Patients will be given all three study drugs and radiation therapy on a monday (unless a monday falls on on a holiday). This will be day 1 of the first treatment cycle. 5-FU is given continuously days 1-14. Bevacizumab is given on day 1. Erlotinib will be given on days 1-14. Radiation therapy will be performed on Days 1-5 and 8-12.

• The following tests and procedures will be performed weekly while participants are receiving study treatment: physical examination, measurement of vital signs, height and weight; performance status; blood work, urine sample.

• At the end of treatment the following tests will be performed: physical examination and measurement of vital signs; performance status; blood work; CT scans of chest, abdomen and pelvis. Patients will also be evaluated for surgery at this time. Patients will be followed every three months for the first three years after surgery, then every 6 months for the next two years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Study of Bevacizumab, Erlotinib and 5-fluorouracil With Concurrent External Beam Radiation Therapy in Locally Advanced Rectal Cancer
• Study Start Date: May 1, 2006
• Actual Primary Completion Date: Apr 1, 2010
• Actual Study Completion Date: Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Chemotherapy and radiation Continuous infusion 5-fluorouracil 225 mg/M2/d, bevacizumab 5 mg/kg IV q 14 days, erlotinib 50-150 mg orally daily for duration of radiation.	Drug: 5-fluorouracil; Given as a 24-hour infusion on days 1-14 of each 14-day cycle for a total of 3 cycles.; Drug: bevacizumab; Given intravenously on day 1 of each 14-day cycle for a total of 3 cycles.; Drug: erlotinib; Taken orally on days 1-14 of each 14-day cycle for a total of 3 cycles.; Procedure: External beam radiation therapy (EBRT); Given on days 1-5 and 8-12

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose (MTD) of Erlotinib When Administered in Combination With 5-fluorouracil (5-FU), Bevacizumab, and External Beam Radiation Therapy [3 years]

   MTD of Erlotinib was determined using a traditional 3 + 3 dose escalation scheme of three dose levels (50,100,150mg). Successive cohorts of 3-6 patients were enrolled into dose escalation cohorts for 14 day cycles. MTD reflects the highest dose of Erlotinib that had ≤1 out of 6 patients with Dose-Limiting Toxicity (DLT) at the highest dose level below the maximally administered dose. The maximally administered dose is the first dose that causes DLT in >33% of patients. DLT was defined as: Any grade 4 neutropenia, Any grade 3 thrombocytopenia, or Any ≥ grade 3 non-hematologic toxicity that results in greater than 7 days interruption in therapy.

Secondary Outcome Measures

1. Summary of Grade 3 or Greater Toxicity [3 years]

   Summary of grade 3 or greater toxicity by grade and type. All adverse events were evaluated using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Grade 3: Severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated.

2. Percentage of Participants With Disease-free Survival [1, 2, 3 years]

   Summary of disease free survival at 1, 2, and 3 years. Disease free survival is the length of time after primary treatment for cancer ends that the participant survives without any clinical signs or symptoms of that cancer. The data is shown of the percentage of participants still in disease free survival at one, two, and three years.

3. Post-operative Complications After Resection of Rectal Cancers Following Preoperative 5-FU, Bevacizumab, Erlotinib, and External Beam Radiation Therapy. [3 years]

   Surgical morbidity following R0 resection with one of the following procedures: abdominal perineal resection, low anterior resection, and low anterior resection with coloanal anastomosis.

Other Outcome Measures

1. Pathologic Complete Response [3 years]

   The number of subjects who achieved a pathologic complete response as determine by pathologist, following completion of the study therapy. Pathologic complete response represents the absence of residual invasive disease in the rectum and in the regional lymph nodes.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed primary adenocarcinoma of the rectum that begins within 15cm of the anal verge as determined by sigmoidoscopy or colonoscopy

• Clinical T3 or T4 tumors as determined by endoscopic ultrasound and/or rectal MRI

• ECOG performance status of 0-2

• 18 years of age or older

• Creatinine of < 2.0

• Adequate hepatic function

• Adequate hematopoietic function

• Use of effective means of contraception in subjects of child-bearing potential

Exclusion Criteria:

• Evidence of metastatic disease as determined by chest/abdominal/pelvic CT or physical exam

• Prior chemotherapy or radiation therapy for treatment of colorectal cancer

• Prior treatment with 5-FU

• Prior treatment with a tyrosine kinase inhibitor, EGFR inhibitor, or VEGF inhibitor

• Patients must not be receiving any other investigational agent

• Prior malignancy within the last 5 years except for completely excised skin cancer, in situ cervical cancer

• Warfarin anticoagulation

• Co-existent malignant disease

• Current or recent participation in a clinical trial (within 4 weeks from the first day of treatment)

• Pregnancy

• Blood pressure of >150/100 mmHg

• Unstable angina

• NYHA Grade II or greater congestive heart failure

• History of myocardial infarction within 6 months

• History of stroke within 6 months

• Clinically significant peripheral vascular disease

• Evidence of bleeding diathesis or coagulopathy

• Presence of central nervous system or brain metastases

• Major surgical procedure, open biopsy, or significant trauma injury within 28 days prior to day 0, anticipation of need for major surgical procedure during the course of the study

• Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to day 0

• Pregnant or lactating

• Urine protein:creatinine ratio > or equal to one at screening

• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 0]

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
2	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
3	Massachusetts General Hospital	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Massachusetts General Hospital
• Beth Israel Deaconess Medical Center
• Dana-Farber Cancer Institute
• Genentech, Inc.

Investigators

• Principal Investigator: Lawrence S. Blaszkowsky, MD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Lawrence S. Blaszkowsky, MD, Assistant Physician, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00307736
• Other Study ID Numbers: 05-345
• First Posted: Mar 28, 2006
• Last Update Posted: May 10, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by Lawrence S. Blaszkowsky, MD, Assistant Physician, Massachusetts General Hospital: Fluorouracil; bevacizumab; erlotinib; external beam radiation therapy; EBRT
• Additional relevant MeSH terms: Rectal Neoplasms; Bevacizumab; Fluorouracil; Erlotinib Hydrochloride

Study Results

Participant Flow

Recruitment Details	This is a single center (institutions comprising Dana Farber Partners/Harvard Cancer Center) trial. Subjects were selected upon referral to the respective clinics of the investigators' institution. Patients Patients were enrolled on to the study between May 2006 and December 2009.

Arm/Group Title	Phase 1 (Erlotinib 50mg)	Phase 1 (100mg Erlotinib)	Phase 1 (150mg Erlotinib)	Phase II (100mg Erlotinib)
Arm/Group Description	Continuous infusion 5-fluorouracil 225 mg/M2/d, bevacizumab 5 mg/kg IV q 14 days, erlotinib 50-150 mg orally daily for duration of radiation. 5-fluorouracil: Given as a 24-hour infusion on days 1-14 of each 14-day cycle for a total of 3 cycles. bevacizumab: Given intravenously on day 1 of each 14-day cycle for a total of 3 cycles. erlotinib: Taken orally on days 1-14 of each 14-day cycle for a total of 3 cycles. External beam radiation therapy (EBRT): Given on days 1-5 and 8-12	Continuous infusion 5-fluorouracil 225 mg/M2/d, bevacizumab 5 mg/kg IV q 14 days, erlotinib 50-150 mg orally daily for duration of radiation. 5-fluorouracil: Given as a 24-hour infusion on days 1-14 of each 14-day cycle for a total of 3 cycles. bevacizumab: Given intravenously on day 1 of each 14-day cycle for a total of 3 cycles. erlotinib: Taken orally on days 1-14 of each 14-day cycle for a total of 3 cycles. External beam radiation therapy (EBRT): Given on days 1-5 and 8-12	Continuous infusion 5-fluorouracil 225 mg/M2/d, bevacizumab 5 mg/kg IV q 14 days, erlotinib 50-150 mg orally daily for duration of radiation. 5-fluorouracil: Given as a 24-hour infusion on days 1-14 of each 14-day cycle for a total of 3 cycles. bevacizumab: Given intravenously on day 1 of each 14-day cycle for a total of 3 cycles. erlotinib: Taken orally on days 1-14 of each 14-day cycle for a total of 3 cycles. External beam radiation therapy (EBRT): Given on days 1-5 and 8-12	Continuous infusion 5-fluorouracil 225 mg/M2/d, bevacizumab 5 mg/kg IV q 14 days, erlotinib 50-150 mg orally daily for duration of radiation. 5-fluorouracil: Given as a 24-hour infusion on days 1-14 of each 14-day cycle for a total of 3 cycles. bevacizumab: Given intravenously on day 1 of each 14-day cycle for a total of 3 cycles. erlotinib: Taken orally on days 1-14 of each 14-day cycle for a total of 3 cycles. External beam radiation therapy (EBRT): Given on days 1-5 and 8-12
Period Title: Overall Study
STARTED	3	3	3	23
COMPLETED	3	3	0	20
NOT COMPLETED	0	0	3	3

Baseline Characteristics

Arm/Group Title	5-fluorocuracil, Bevacizumab, Erlotinib and Radiation
Arm/Group Description	All patients receive chemoradiation with continuous infusion 5-fluorouracil, bevacizumab and erlotinib.
Overall Participants	32
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	28 87.5%
>=65 years	4 12.5%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	53.5
Sex: Female, Male (Count of Participants)
Female	8 25%
Male	24 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	28 87.5%
Not Hispanic or Latino	2 6.3%
Unknown or Not Reported	2 6.3%
Race/Ethnicity, Customized (Count of Participants)
White	29 90.6%
Other	3 9.4%
Region of Enrollment (participants) [Number]
United States	32 100%
Stage Grouping (Count of Participants)
II	11 34.4%
III	21 65.6%
Clinical staging (Count of Participants)
T3N0	6 18.8%
T3N1	15 46.9%
T3N2M0	4 12.5%
T3Nx	4 12.5%
T4N0	2 6.3%
T4N1	1 3.1%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of Erlotinib When Administered in Combination With 5-fluorouracil (5-FU), Bevacizumab, and External Beam Radiation Therapy
Description	MTD of Erlotinib was determined using a traditional 3 + 3 dose escalation scheme of three dose levels (50,100,150mg). Successive cohorts of 3-6 patients were enrolled into dose escalation cohorts for 14 day cycles. MTD reflects the highest dose of Erlotinib that had ≤1 out of 6 patients with Dose-Limiting Toxicity (DLT) at the highest dose level below the maximally administered dose. The maximally administered dose is the first dose that causes DLT in >33% of patients. DLT was defined as: Any grade 4 neutropenia, Any grade 3 thrombocytopenia, or Any ≥ grade 3 non-hematologic toxicity that results in greater than 7 days interruption in therapy.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	5-FU, Bevacizumab, Erlotinib and Radiation
Arm/Group Description	All patients received chemoradiation with continuous infusion 5-fluorouracil, bevacizumab and erlotinib. (phase 1 participants)
Measure Participants	9
Number [mg]	100

2. Secondary Outcome

Title	Summary of Grade 3 or Greater Toxicity
Description	Summary of grade 3 or greater toxicity by grade and type. All adverse events were evaluated using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Grade 3: Severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Toxicity was grouped together for all phase I dose cohorts and the phase II cohort in order to summarize all the grade 3 or greater toxicities associated with the combined study therapy, instead of focusing on the dose limiting toxicities from the phase 1 dose escalation of Erlotinib. Grade 3 or higher AE data is not available by dose cohort.

Arm/Group Title	Grade 3	Grade 4
Arm/Group Description	Continuous infusion 5-fluorouracil 225 mg/M2/d, bevacizumab 5 mg/kg IV q 14 days, erlotinib 50-150 mg orally daily for duration of radiation. 5-fluorouracil: Given as a 24-hour infusion on days 1-14 of each 14-day cycle for a total of 3 cycles. bevacizumab: Given intravenously on day 1 of each 14-day cycle for a total of 3 cycles. erlotinib: Taken orally on days 1-14 of each 14-day cycle for a total of 3 cycles. External beam radiation therapy (EBRT): Given on days 1-5 and 8-12	Continuous infusion 5-fluorouracil 225 mg/M2/d, bevacizumab 5 mg/kg IV q 14 days, erlotinib 50-150 mg orally daily for duration of radiation. 5-fluorouracil: Given as a 24-hour infusion on days 1-14 of each 14-day cycle for a total of 3 cycles. bevacizumab: Given intravenously on day 1 of each 14-day cycle for a total of 3 cycles. erlotinib: Taken orally on days 1-14 of each 14-day cycle for a total of 3 cycles. External beam radiation therapy (EBRT): Given on days 1-5 and 8-12
Measure Participants	32	32
Lymphopenia	16 50%	5 NaN
Diarrhea w/o prior colostomy	6 18.8%	0 NaN
Hypophosphatemia	3 9.4%	0 NaN
Rash: acne/acneiform	2 6.3%	0 NaN
ALT-SGPT	1 3.1%	0 NaN
AST-SGOT	1 3.1%	0 NaN
Cardiac-ischemia	1 3.1%	0 NaN
Colitis	1 3.1%	0 NaN
Dehydration	1 3.1%	0 NaN
Fatigue	1 3.1%	0 NaN
Febrile neutropenia	0 0%	1 NaN
Hypertension	1 3.1%	0 NaN
Hyperuricemia	0 0%	1 NaN
Hypokalemia	1 3.1%	0 NaN
Hyponatremia	1 3.1%	0 NaN
Muco/stomatitis (symptom) oral cavity	1 3.1%	0 NaN
Muco/stomatitis by exam-oral cavity	1 3.1%	0 NaN
Proteinuria	1 3.1%	0 NaN
Radiation dermatitis	1 3.1%	0 NaN
Rash/desquamation	1 3.1%	0 NaN
Rectum-pain	1 3.1%	0 NaN

3. Secondary Outcome

Title	Percentage of Participants With Disease-free Survival
Description	Summary of disease free survival at 1, 2, and 3 years. Disease free survival is the length of time after primary treatment for cancer ends that the participant survives without any clinical signs or symptoms of that cancer. The data is shown of the percentage of participants still in disease free survival at one, two, and three years.
Time Frame	1, 2, 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	5-fluorocuracil, Bevacizumab, Erlotinib and Radiation
Arm/Group Description	Continuous infusion 5-fluorouracil 225 mg/M2/d, bevacizumab 5 mg/kg IV q 14 days, erlotinib 50-150 mg orally daily for duration of radiation. 5-fluorouracil: Given as a 24-hour infusion on days 1-14 of each 14-day cycle for a total of 3 cycles. bevacizumab: Given intravenously on day 1 of each 14-day cycle for a total of 3 cycles. erlotinib: Taken orally on days 1-14 of each 14-day cycle for a total of 3 cycles. External beam radiation therapy (EBRT): Given on days 1-5 and 8-12
Measure Participants	32
1 Year	93.4 291.9%
2 Years	83.4 260.6%
3 Years	75.5 235.9%

4. Secondary Outcome

Title	Post-operative Complications After Resection of Rectal Cancers Following Preoperative 5-FU, Bevacizumab, Erlotinib, and External Beam Radiation Therapy.
Description	Surgical morbidity following R0 resection with one of the following procedures: abdominal perineal resection, low anterior resection, and low anterior resection with coloanal anastomosis.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Total study population excluding one patient who refused surgery.

Arm/Group Title	Surgery, 5-fluorocuracil, Bevacizumab, Erlotinib and Radiation
Arm/Group Description	Patients undergoing R0 resection following chemotherapy and radiation. Continuous infusion 5-fluorouracil 225 mg/M2/d, bevacizumab 5 mg/kg IV q 14 days, erlotinib 50-150 mg orally daily for duration of radiation. 5-fluorouracil: Given as a 24-hour infusion on days 1-14 of each 14-day cycle for a total of 3 cycles. bevacizumab: Given intravenously on day 1 of each 14-day cycle for a total of 3 cycles. erlotinib: Taken orally on days 1-14 of each 14-day cycle for a total of 3 cycles. External beam radiation therapy (EBRT): Given on days 1-5 and 8-12
Measure Participants	31
anastomotic leaks	4 12.5%
intra-abdominal infection	2 6.3%
wound infections	2 6.3%
pulmonary embolus	1 3.1%
small bowel obstruction	1 3.1%
urinary obstruction/retention	5 15.6%
fever	1 3.1%

5. Other Pre-specified Outcome

Title	Pathologic Complete Response
Description	The number of subjects who achieved a pathologic complete response as determine by pathologist, following completion of the study therapy. Pathologic complete response represents the absence of residual invasive disease in the rectum and in the regional lymph nodes.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Patients who completed study therapy.

Arm/Group Title	Completed Study Therapy	Underwent Resection	Treated at MTD
Arm/Group Description	Patients who had pathologic complete response following completion of study therapy. All patients receive chemo-radiation with continuous infusion 5-fluorouracil, bevacizumab and erlotinib.	Patients who underwent R0 resection following study therapy All patients receive chemoradiation with continuous infusion 5-fluorouracil, bevacizumab and erlotinib.	Patients who were treated with erlotinib at maximum tolerated dose, along with standard study therapy. All patients receive chemoradiation with continuous infusion of 5-fluorouracil, bevacizumab and erlotinib.
Measure Participants	27	31	26
Count of Participants [Participants]	9 28.1%	10 NaN	7 NaN

Adverse Events

Time Frame	3 years
Adverse Event Reporting Description	Patients were evaluated for adverse events at each study visit for the duration of their participation in the study. Safety evaluations consisted of medical interviews, recording of adverse events, physical examinations, blood pressure, and laboratory measurements. Patients discontinued from the treatment phase of the study for any reason would be evaluated ~30 days. Adverse event data was aggregated for phase 1 and 2 portion of the study. Adverse event data by dose cohort is not available.
Arm/Group Title	5-fluorocuracil, Bevacizumab, Erlotinib and Radiation
Arm/Group Description	Continuous infusion 5-fluorouracil 225 mg/M2/d, bevacizumab 5 mg/kg IV q 14 days, erlotinib 50-150 mg orally daily for duration of radiation. 5-fluorouracil: Given as a 24-hour infusion on days 1-14 of each 14-day cycle for a total of 3 cycles. bevacizumab: Given intravenously on day 1 of each 14-day cycle for a total of 3 cycles. erlotinib: Taken orally on days 1-14 of each 14-day cycle for a total of 3 cycles. External beam radiation therapy (EBRT): Given on days 1-5 and 8-12
All Cause Mortality
	5-fluorocuracil, Bevacizumab, Erlotinib and Radiation
	Affected / at Risk (%)	# Events
Total	0/32 (0%)
Serious Adverse Events
	5-fluorocuracil, Bevacizumab, Erlotinib and Radiation
	Affected / at Risk (%)	# Events
Total	8/32 (25%)
Blood and lymphatic system disorders
Lymphopenia	5/32 (15.6%)	5
Cardiac disorders
Cardiac Ischemia	1/32 (3.1%)	1
Infections and infestations
Febrile Neutropenia	1/32 (3.1%)	1
Metabolism and nutrition disorders
Hyperuricemia	1/32 (3.1%)	1
Other (Not Including Serious) Adverse Events
	5-fluorocuracil, Bevacizumab, Erlotinib and Radiation
	Affected / at Risk (%)	# Events
Total	32/32 (100%)
Blood and lymphatic system disorders
Hemoglobin	12/32 (37.5%)	22
Hemorrhage-other	2/32 (6.3%)	2
Hypoalbuminemia	7/32 (21.9%)	10
Leukocytes	15/32 (46.9%)	26
Lymphopenia	29/32 (90.6%)	73
Neutrophils	2/32 (6.3%)	3
Platelets	2/32 (6.3%)	2
Cardiac disorders
Hypertension	3/32 (9.4%)	4
Eye disorders
Vision-blurred	2/32 (6.3%)	2
Gastrointestinal disorders
Abdomen pain	12/32 (37.5%)	19
Anorexia	16/32 (50%)	28
Anus- pain	3/32 (9.4%)	3
Constipation	7/32 (21.9%)	11
Dehydration	7/32 (21.9%)	9
Diarrhea w/o prior colostomy	29/32 (90.6%)	65
Dry mouth	3/32 (9.4%)	4
Dyspepsia	3/32 (9.4%)	6
Dysphagia	3/32 (9.4%)	4
Flatulence	4/32 (12.5%)	8
GI-other	6/32 (18.8%)	10
Hemorrhoids	7/32 (21.9%)	10
Mucositis/stomatitis (symptom) oral cavity	11/32 (34.4%)	23
Mucositis/stomatitis by exam- oral cavity	8/32 (25%)	13
Nausea	24/32 (75%)	41
Oral cavity- pain	2/32 (6.3%)	3
Oral gums- pain	2/32 (6.3%)	2
Rectum- hemorrhage	13/32 (40.6%)	21
Rectum- pain	24/32 (75%)	38
Taste disturbance	4/32 (12.5%)	5
Vomiting	4/32 (12.5%)	4
General disorders
Fatigue	29/32 (90.6%)	67
Fever w/o neutropenia	3/32 (9.4%)	6
Insomnia	8/32 (25%)	15
Pain-other	2/32 (6.3%)	3
Rigors/chills	7/32 (21.9%)	8
Sweating	2/32 (6.3%)	2
Weight loss	14/32 (43.8%)	22
Immune system disorders
Allergic reaction	3/32 (9.4%)	3
Allergic rhinitis	2/32 (6.3%)	2
Metabolism and nutrition disorders
Alkaline phosphatase	4/32 (12.5%)	6
ALT- SGPT	8/32 (25%)	10
AST- SGOT	10/32 (31.3%)	13
Bicarbonate	2/32 (6.3%)	3
Bilirubin	5/32 (15.6%)	9
Creatinine	2/32 (6.3%)	2
Hyperglycemia	17/32 (53.1%)	28
Hyperkalemia	3/32 (9.4%)	3
Hypocalcemia	7/32 (21.9%)	8
Hypoglycemia	4/32 (12.5%)	4
Hypokalemia	4/32 (12.5%)	5
Hypomagnesemia	4/32 (12.5%)	4
Hyponatremia	13/32 (40.6%)	16
Hypophosphatemia	5/32 (15.6%)	5
Proteinuria	6/32 (18.8%)	9
Musculoskeletal and connective tissue disorders
Back- pain	2/32 (6.3%)	3
Extremity-limb- pain	3/32 (9.4%)	5
Muscle- pain	2/32 (6.3%)	3
Nervous system disorders
Confusion	2/32 (6.3%)	2
Dizziness	5/32 (15.6%)	8
Head/headache	6/32 (18.8%)	7
Memory impairment	2/32 (6.3%)	4
Neuropathy-sensory	3/32 (9.4%)	4
Psychiatric disorders
Anxiety	3/32 (9.4%)	3
Depression	2/32 (6.3%)	3
Renal and urinary disorders
Cystitis	2/32 (6.3%)	3
Renal/GU-other	2/32 (6.3%)	2
Urinary frequency/urgency	6/32 (18.8%)	12
Urinary retention	2/32 (6.3%)	3
Reproductive system and breast disorders
Pelvic- pain	3/32 (9.4%)	5
Proctitis	2/32 (6.3%)	2
Vagina- pain	2/32 (6.3%)	4
Respiratory, thoracic and mediastinal disorders
Cough	2/32 (6.3%)	4
Nose- hemorrhage	9/32 (28.1%)	14
Throat/pharynx/larynx- pain	2/32 (6.3%)	3
Skin and subcutaneous tissue disorders
Dry skin	3/32 (9.4%)	4
Flushing	2/32 (6.3%)	3
Hand-foot reaction	4/32 (12.5%)	5
Pruritus/itching	5/32 (15.6%)	7
Radiation dermatitis	10/32 (31.3%)	15
Rash/desquamation	5/32 (15.6%)	15
Rash: acne/acneiform	23/32 (71.9%)	59
Skin-other	8/32 (25%)	12
Urticaria	2/32 (6.3%)	3

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.