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PANVAC-V and PANVAC-F Vaccines Plus Sargramostim to Treat Advanced Cancer

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00088413
Collaborator
(none)
51
Enrollment
1
Location
1
Arm
166.3
Actual Duration (Months)
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Background:

  • Many cancers produce two proteins, carcinoembryonic antigen (CEA) and mucin-1 (MUC-1).

  • The PANVAC-V (PANVAC vaccinia) priming vaccine and PANVAC-F (PANVAC fowlpox) boosting vaccine contain human genes that cause production of CEA and MUC-1, which can be used as a target for the immune system to attack the cancer. The vaccines also contain genes that cause production of other proteins that enhance immune activity.

  • Sargramostim is a protein that boosts the immune system.

Objectives:

  • To evaluate the safety and effectiveness of PANVAC-V and PANVAC-F in patients with advanced cancer.

  • To document the immune response to the vaccines and any anti-tumor responses that may occur.

Eligibility: Patients 18 years of age and older with advanced cancer whose tumors produce CEA or MUC-1 protein

Design:

  • This trial has three cohorts: the first cohort includes 10 patients with advanced colorectal cancer and 10 to 15 patients with any advanced non-colorectal cancer that produces either EA or mitochondrial Ca2+ uniporter 1 (MCU-1); the second cohort includes 12 patients with advanced breast cancer and the third cohort includes 14 patients with advanced ovarian cancer.

  • All patients receive PANVAC-V on study day 1, followed by PANVAC-F on days 15, 29 and 43 then every 28 days for up to 12 vaccines followed by every 3 months until disease progression or toxicity. The vaccines are given by injection under the skin. Sargramostim is injected at the vaccination site on the day of each vaccination and for the next 3 days following vaccination.

  • Patients whose scans show that their disease has progressed, but who are otherwise clinically stable may revert back to monthly injections.

  • Patients undergo apheresis to collect white blood cells (lymphocytes) on day 1 and day 71 of the study to measure the immune response to the treatment. Blood is collected through a needle placed in one arm and directed through a cell separator machine where the lymphocytes are extracted. The rest of the blood components are returned to the patient through the same needle.

  • Patients are monitored with frequent blood tests and periodic imaging tests (scans) to monitor for safety and the response to treatment.

Condition or Disease Intervention/Treatment Phase
  • Biological: PANVAC-V
  • Biological: PANVAC-F
  • Drug: Sargramostim (GM-CSF, Leukine)
 Phase 1/Phase 2

Detailed Description

Background:

  • Carcinoembryonic antigen (CEA) and mucin-1 (MUC-1) are overexpressed in multiple adenocarcinomas.

  • Pox viral vectors can induce a strong immune response to CEA and MUC-1.

  • The use of agonist epitopes within the tumor associated antigen (TAA) can induce a better immune response than native peptides and have been associated with clinical responses

  • Heterologous prime and boost regimens are superior in terms of generalizing immune responses; and this may translate into improved clinical responses

  • The use of granulocyte-macrophage colony-stimulating factor (GM-CSF) does not add significant toxicity and in pre-clinical models is essential for induction for optimal immune responses.

  • It is possible by using vectors directed against TAA that there may be additive or synergistic immune responses and this may be important in overcoming antigenic escape variance

  • Evidence of clinical benefit has been noted in some patients treated with this vaccine

Objectives:

  • For colorectal cancer and non-colorectal cancer Cohort: To evaluate the safety and tolerability of the vaccine.

  • For the Ovarian Cancer and Breast Cancer Cohorts: To evaluate clinical response to the vaccine.

Eligibility:

  • In the first cohort (colorectal and non-colorectal cancer), histologically confirmed adenocarcinoma that is CEA or MUC-1 positive described as metastatic disease (measurable or evaluable) or metastatic disease documented by biopsy but not evaluable by imaging (e.g. small volume peritoneal disease)

  • For the ovarian and breast cancer cohorts, patients must have evaluable disease

  • Normal organ function, Eastern Cooperative Oncology Group (ECOG) 0-1

Design:

  • This is a non-randomized three cohort, pilot trial of pox viral vaccines that contain the transgenes for CEA and MUC-1 (both with modified human leukocyte antigen A2 (HLA-A2) agonist epitopes) as well as 3 human T-cell costimulatory molecules, B7-1, ICAM-1 (CD54), and LFA-3 (CD58) [PANVAC(TM)-V (vaccinia) and PANVAC(TM)-F (fowlpox)] in patients with metastatic carcinoma that express CEA or MUC-1 antigen.

  • The first cohort will enroll 10 patients with metastatic colorectal adenocarcinoma and 10-15 patients with any metastatic non-colorectal carcinoma that expresses either CEA or MUC-1. .

  • The second cohort will enroll 12 patients with metastatic breast carcinoma and 14 patients with metastatic ovarian carcinoma.

  • All patients will receive the same vaccines on the same schedule. PANVAC(TM)-V (vaccinia) subcutaneously (s.c.) scheduled on day 1, followed by PANVAC(TM)-F (fowlpox) s.c. scheduled on days 15, 29, and 43 then every 28 days for up to 12 vaccines followed by every 3 months until disease progression or toxicity.

  • Sargramostim (100 micro g) will be given at the site of the vaccination (PANVAC-V and PANVAC-F) on each vaccination day and for three consecutive days thereafter.

  • Patients who have radiographic evidence of progressive disease, but who are otherwise clinically stable may revert back to monthly vaccinations.

Study Design

Study Type:
Interventional
Actual Enrollment :
51 participants
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open Label Pilot Study to Evaluate the Safety and Tolerability of PANVAC-V (Vaccinia) and PANVAC-F (Fowlpox) in Combination With Sargramostim in Adults With Metastatic Carcinoma
Actual Study Start Date :
Jul 21, 2004
Actual Primary Completion Date :
Apr 1, 2018
Actual Study Completion Date :
May 31, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: All Cohorts: Colorectal, Non-Colorectal, Breast, and Ovarian

All cohorts receive the same intervention (Cohort 1: Colorectal arm, non-colorectal cancers; Cohort 2: breast cancer; Cohort 3: ovarian cancers)

Biological: PANVAC-V
Patients receive 2 x 10(8) pfu PANVAC-V (vaccinia) subcutaneously on Day 1.

Biological: PANVAC-F
Patients receive 1 x 10(9) pfu PANVAC-F (fowlpox) or about days 15, 29, and 43 then every month for 12 doses then every 3 months until disease progression or toxicity.

Drug: Sargramostim (GM-CSF, Leukine)
100g sargramostim will be given subcutaneously at the site of the vaccination on each vaccination day and for three consecutive days thereafter.
Other Names:
  • Granulocyte-macrophage colony-stimulating factor

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Complete Responses (CRs), Partial Responses (PRs,) Stable Disease and Progressive Disease in the Ovarian Cancer and Breast Cancer Cohorts [Approximately 6 months while on trial]

      Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response is disappearance of all clinical and laboratory signs and symptoms of disease for a minimum of 4 weeks during which no new lesions may appear. Partial Response is a minimum of 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Stable disease is neither sufficient shrinkage to qualify for partial response nor progressive disease, taking as reference the smallest sum longest diameter since the treatment started. Progressive disease is a minimum of 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new measurable lesions.

    2. Percentage of Vaccines Associated With Grade 1 and Grade 2 Adverse Events Related to Vaccine in the Colorectal Cancer and Non-Colorectal Cancer Arm/Group [Approximately 6 months while on trial]

      Grade 1 (mild) and Grade 2 (moderate) adverse events were assessed by the Common Terminology Criteria in Adverse Events (CTCAE) v3.0 if reported prior to August 1, 2010 and CTCAE v4.0 if reported after. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

    Secondary Outcome Measures

    1. Percentage of Participants With Grade 1 and Grade 2 Adverse Events Possibly, Likely, or Definitely Related to Vaccine in the Breast Cancer and Ovarian Cancer Cohorts [Approximately 2 months while on trial]

      Vaccines were administered to participants and Grade 1 (mild) and Grade 2 (moderate) adverse events were assessed by the Common Terminology Criteria in Adverse Events (CTCAE) v3.0 if reported prior to August 1, 2010 and CTCAE v4.0 if reported after. Common Terminology Criteria in Adverse Events. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

    2. Number of Participants With Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE) v3.0 and v4.0 [Date consent signed to date off study, approximately 164 months and 10 days]

      Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE) v3.0 if reported prior to August 1, 2010 and CTCAE v4.0 if reported after. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

    3. Number of Participants With an Positive Immune Response to Carcinoembryonic Antigen (CEA) Peptide and/or Protein in the Colorectal Cancer and Non-colorectal Cancer Cohort Post Vaccination [post vaccination (up to Day 84)]

      Immune response in human leukocyte antigens (HLA)-A2 positive patients to carcinoembryonic antigen (CEA) was assessed by enzyme-linked immunospot assay (ELISPOT) analysis. A positive immune response was defined as a >2x fold increase in the number of interferon gamma producing cells.

    4. Number of Participants With an Positive Immune Response to Carcinoembryonic Antigen (CEA) Peptide and/or Protein in the Breast Cancer and Ovarian Cancer Cohorts Post Vaccination [post vaccination (up to Day 84)]

      Immune response in human leukocyte antigens (HLA)-A2 positive patients to carcinoembryonic antigen (CEA) was assessed by enzyme-linked immunospot assay (ELISPOT) analysis. A positive immune response was defined as a >2x fold increase in the number of interferon gamma producing cells.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 100 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    • INCLUSION CRITERIA:

    1. Histologically confirmed carcinoma that for patients in the first cohort (colorectal and non-colorectal cancer) is carcinoembryonic antigen (CEA) or mucin-1 (MUC-1) positive. Tumor that has been shown to express CEA or MUC-1 (greater than or equal to 20 % of cells) by immunohistochemical techniques or patients that have had an elevated serum CEA (greater than 5 microgram/L) at any point during their disease course. For patients in the ovarian and breast cancer cohorts, as greater than 95% of these express MUC-1 or CEA, we will not require staining prior to coming onto trial.

    2. Patients must have completed at least one fluorouracil (5-FU) containing chemotherapy regimen (e.g. 5-FU/leucovorin (LV) with or without either irinotecan or oxaliplatin) for the colorectal cancer arm, or either failed or not be a candidate for therapy of proven efficacy for non-colorectal, breast, or ovarian cancer.

    3. 18 years of age or greater.

    4. All patients enrolled on the colorectal/non-colorectal cohort with colorectal adenocarcinoma cohort must be human leukocyte antigen A2 (HLA-A2) positive.

    5. At least 10 patients enrolled on the colorectal/non-colorectal cohort with non-colorectal adenocarcinoma cohort must be HLA-A2 positive.

    6. Patients in the breast cohort and the ovarian cohorts are not required to be HLA-A2 positive.

    G. For the colorectal and non-colorectal cancer cohort, patients will be required to have:

    metastatic disease (measurable or evaluable), metastatic disease documented by biopsy but not evaluable by imaging (e.g. small volume peritoneal disease), and patients with surgically resected metastatic disease at high risk of relapse. For the ovarian cohort and the breast cancer cohort, patients will be required to have evaluable disease.

    1. Able to understand and give informed consent.

    2. Able to avoid close household contact (close household contacts are those who share housing or have close physical contact) for at least three weeks after recombinant vaccinia vaccination with persons with active or a history of eczema or other eczematoid skin disorders; those with other acute, chronic or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds) until condition resolves; pregnant or nursing women; children 3 years of age and under; and immunodeficient or immunosuppressed persons (by disease or therapy), including human immunodeficiency virus (HIV) infection.

    3. Eastern Oncology Cooperative Group (ECOG) performance status of 0 - 1.

    4. Serum creatinine not above the institution limits of normal, and aspartate aminotransferase (AST) less than or equal to twice the upper limits of normal OR creatinine clearance on a 24 hour urine collection of greater than or equal to 60 mL/min.

    5. Total bilirubin within the institution limits of normal OR patients with Gilbert's syndrome, a total bilirubin less than or equal to 3.0

    6. Recovered completely from any reversible toxicity associated with recent therapy. Typically this is 3-4 weeks for patients who most recently received cytotoxic therapy except for the nitrosoureas and mitomycin C for which 6 weeks is needed for recovery.

    N. Hematological eligibility parameters (within 16 days of starting therapy):

    • Granulocyte count greater than or equal to 1,500/mm(3)

    • Platelet count greater than or equal to 100,000/mm(3)

    • Hemoglobin (Hgb) greater than or equal to 10 Gm/dL

    1. Prior immune therapy with related vaccinia and fowlpox vaccines or antigen-specific peptides is allowed.

    2. Men and women must agree to use effective birth control or abstinence during and for a period of 4 months after the last vaccination therapy.

    3. Patients with prostate cancer must continue to receive gonadotropin-releasing hormone (GnRH) agonist therapy (unless orchiectomy has been done).

    4. Patients should appear clinically stable (in the opinion of the principal investigator) to complete the full 3 month course of vaccination with an anticipated survival of 6 months or longer.

    EXCLUSION CRITERIA:
    1. Patients should have no evidence of being immunocompromised as listed below.

    • Human immunodeficiency virus positivity due to the potential for decreased tolerance and risk for severe side effects

    • Active autoimmune diseases requiring treatment or a history of autoimmune disease that might be stimulated by vaccine treatment. This requirement is due to the potential risks of exacerbating autoimmunity. Patients with endocrine disease that is controlled by replacement therapy including thyroid disease and adrenal disease and vitiligo may be enrolled.

    1. Concurrent use of systemic steroids, except for physiologic doses for systemic steroid replacement or local (topical, nasal, or inhaled) steroid use. Limited doses systemic steroids to prevent intravenous (IV) contrast, allergic reaction, or anaphylaxis (in patients who have known contrast allergies) are allowed.

    2. History of allergy or untoward reaction to prior vaccination with vaccinia virus.

    3. Pregnant or breast-feeding women.

    4. Altered immune function, including immunodeficiency or history of immunodeficiency; eczema; history of eczema, or other eczematoid skin disorders; or those with acute, chronic or exfoliative skin conditions (e.g. atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds).

    5. Serious intercurrent medical illness which would interfere with the ability of the patient to carry out the treatment program, including, but not limited to, inflammatory bowel disease, Crohn's disease, ulcerative colitis, or active diverticulitis

    6. Patients with a history of cardiomyopathy or symptomatic congestive heart failure (unless stable on treatment), symptomatic arrhythmia not controlled by medication. Unstable atherosclerotic heart disease (e.g. unstable angina) who require active intervention and history of myocardial infarction or embolic stroke within the past 6 months.

    7. Clinically active brain metastasis, or a history of encephalitis, multiple sclerosis, or seizures within the last year (from seizure disorder or brain metastasis).

    8. Medical conditions, which, in the opinion of the investigators would jeopardize the patient or the integrity of the data obtained.

    9. Concurrent chemotherapy; an exception to this is to allow for patients with breast cancer who are receiving trastuzumab, to continue therapy with trastuzumab while receiving the vaccine treatment.

    10. Serious hypersensitivity reaction to egg products.

    11. Clinically significant cardiomyopathy requiring treatment.

    12. Chronic hepatitis infection, including B and C, because of potential immune impairment.

    13. Although topical steroids are allowed, steroid eye drop are contraindicated.

    14. Cardiac complications, including recent myocardial infarction or cerebrovascular accident within one year, and/or unstable or uncontrolled angina.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda Maryland United States 20892

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: James L Gulley, M.D., National Cancer Institute (NCI)

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    James Gulley, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC)
    ClinicalTrials.gov Identifier:
    NCT00088413
    Other Study ID Numbers:
    • 040246
    • 04-C-0246
    • NCT00091000
    First Posted:
    Jul 26, 2004
    Last Update Posted:
    Apr 16, 2019
    Last Verified:
    Apr 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by James Gulley, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC)
    CEA
    Vaccine
    Immunotherapy
    MUC-1
    Cancer
    Adenocarcinoma
    Metastatic Adenocarcinoma
    Additional relevant MeSH terms:
    Adenocarcinoma
    Molgramostim
    Sargramostim

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Colorectal Cancer Cohort Non-Colorectal Cancer Cohort Breast Cohort Ovarian Cohort
    Arm/Group Description Patients with histologically confirmed measurable or evaluable metastatic colorectal cancer or patients with surgically resected metastatic disease at high risk for recurrence who had completed at least one 5-fluorouracil/(5-FU) containing chemotherapy regimen (e.g., 5-fluorouracil/leucovorin (5-FU/LV) with or without either irinotecan or oxaliplatin or patients that have had an elevated serum CEA (>5 ugg/L) at any point during their disease course who have failed or not a candidate for standard therapy. Patients with histologically confirmed measurable or evaluable metastatic non-colorectal cancer or patients with surgically resected metastatic disease at high risk for recurrence who had completed at least one 5-fluorouracil/(5-FU) containing chemotherapy regimen (e.g., 5-fluorouracil/leucovorin (5-FU/LV) with or without either irinotecan or oxaliplatin or patients that have had an elevated serum CEA (>5 ugg/L) at any point during their disease course who have failed or not a candidate for standard therapy. Patients with evaluable, metastatic breast cancer who have failed or not a candidate for standard therapy. Patients with evaluable, metastatic ovarian cancer who have failed or not a candidate for standard therapy.
    Period Title: Overall Study
    STARTED 10 15 12 14
    COMPLETED 0 0 0 0
    NOT COMPLETED 10 15 12 14

    Baseline Characteristics

    Arm/Group Title Colorectal Cancer Cohort Non-Colorectal Cancer Cohort Breast Cohort Ovarian Cohort Total
    Arm/Group Description Patients with histologically confirmed measurable or evaluable colorectal cancer or patients with surgically resected metastatic disease at high risk for recurrence who had completed at least one 5-fluorouracil/(5-FU) containing chemotherapy regimen (e.g., 5-fluorouracil/leucovorin (5-FU/LV) with or without either irinotecan or oxaliplatin or patients that have had an elevated serum CEA (>5 ugg/L) at any point during their disease course who have failed or not a candidate for standard therapy. Patients with histologically confirmed measurable or evaluable metastatic non-colorectal cancer or patients with surgically resected metastatic disease at high risk for recurrence who had completed at least one 5-fluorouracil/(5-FU) containing chemotherapy regimen (e.g., 5-fluorouracil/leucovorin (5-FU/LV) with or without either irinotecan or oxaliplatin or patients that have had an elevated serum CEA (>5 ugg/L) at any point during their disease course who have failed or not a candidate for standard therapy. Patients with evaluable, metastatic breast cancer who have failed or not a candidate for standard therapy. Patients with evaluable, metastatic ovarian cancer who have failed or not a candidate for standard therapy. Total of all reporting groups
    Overall Participants 10 15 12 14 51
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    8
    80%
    12
    80%
    10
    83.3%
    12
    85.7%
    42
    82.4%
    >=65 years
    2
    20%
    3
    20%
    2
    16.7%
    2
    14.3%
    9
    17.6%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    52.4
    (12.2)
    57.6
    (7.91)
    56.5
    (11.8)
    54.8
    (9.0)
    55.6
    (10.0)
    Sex: Female, Male (Count of Participants)
    Female
    4
    40%
    13
    86.7%
    12
    100%
    14
    100%
    43
    84.3%
    Male
    6
    60%
    2
    13.3%
    0
    0%
    0
    0%
    8
    15.7%
    Race/Ethnicity, Customized (Count of Participants)
    Hispanic or Latino
    1
    10%
    0
    0%
    0
    0%
    0
    0%
    1
    2%
    Not Hispanic or Latino
    9
    90%
    15
    100%
    12
    100%
    14
    100%
    50
    98%
    Asian
    0
    0%
    1
    6.7%
    1
    8.3%
    0
    0%
    2
    3.9%
    Black or African-American
    0
    0%
    1
    6.7%
    1
    8.3%
    0
    0%
    2
    3.9%
    White
    10
    100%
    12
    80%
    0
    0%
    0
    0%
    22
    43.1%
    Unknown or Not Reported
    0
    0%
    1
    6.7%
    0
    0%
    0
    0%
    1
    2%
    Region of Enrollment (Count of Participants)
    United States
    10
    100%
    15
    100%
    12
    100%
    14
    100%
    51
    100%
    Number of Participants with Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 0-1 (Count of Participants)
    Grade 0
    4
    40%
    5
    33.3%
    2
    16.7%
    5
    35.7%
    16
    31.4%
    Grade 1
    6
    60%
    10
    66.7%
    10
    83.3%
    9
    64.3%
    35
    68.6%
    Number of Participants with Prior Therapy (Count of Participants)
    No prior chemotherapy
    0
    0%
    0
    0%
    1
    8.3%
    0
    0%
    1
    2%
    Chemotherapy (1 regimen)
    2
    20%
    5
    33.3%
    1
    8.3%
    1
    7.1%
    9
    17.6%
    Chemotherapy (2 regimens)
    3
    30%
    6
    40%
    2
    16.7%
    1
    7.1%
    12
    23.5%
    Chemotherapy (≥3 regimens)
    5
    50%
    4
    26.7%
    8
    66.7%
    12
    85.7%
    29
    56.9%
    Radiation
    2
    20%
    3
    20%
    8
    66.7%
    0
    0%
    13
    25.5%
    Number of Participants with a Primary Tumor (Count of Participants)
    Colorectal
    10
    100%
    0
    0%
    0
    0%
    0
    0%
    10
    19.6%
    Gastric
    0
    0%
    3
    20%
    0
    0%
    0
    0%
    3
    5.9%
    Pancreatic
    0
    0%
    2
    13.3%
    0
    0%
    0
    0%
    2
    3.9%
    Appendiceal
    0
    0%
    2
    13.3%
    0
    0%
    0
    0%
    2
    3.9%
    Esophageal adenocarcinoma
    0
    0%
    1
    6.7%
    0
    0%
    0
    0%
    1
    2%
    Ovarian
    0
    0%
    3
    20%
    0
    0%
    14
    100%
    17
    33.3%
    Breast
    0
    0%
    2
    13.3%
    12
    100%
    0
    0%
    14
    27.5%
    Lung
    0
    0%
    2
    13.3%
    0
    0%
    0
    0%
    2
    3.9%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Complete Responses (CRs), Partial Responses (PRs,) Stable Disease and Progressive Disease in the Ovarian Cancer and Breast Cancer Cohorts
    Description Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response is disappearance of all clinical and laboratory signs and symptoms of disease for a minimum of 4 weeks during which no new lesions may appear. Partial Response is a minimum of 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Stable disease is neither sufficient shrinkage to qualify for partial response nor progressive disease, taking as reference the smallest sum longest diameter since the treatment started. Progressive disease is a minimum of 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new measurable lesions.
    Time Frame Approximately 6 months while on trial

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Breast Cancer Cohort Ovarian Cancer Cohort
    Arm/Group Description Patients with evaluable, metastatic breast cancer who have failed or not a candidate for standard therapy. Patients with evaluable, metastatic ovarian cancer who have failed or not a candidate for standard therapy.
    Measure Participants 12 14
    Complete Response
    1
    10%
    0
    0%
    Partial Response
    0
    0%
    0
    0%
    Stable Disease
    4
    40%
    3
    20%
    Progressive Disease
    7
    70%
    11
    73.3%
    2. Primary Outcome
    Title Percentage of Vaccines Associated With Grade 1 and Grade 2 Adverse Events Related to Vaccine in the Colorectal Cancer and Non-Colorectal Cancer Arm/Group
    Description Grade 1 (mild) and Grade 2 (moderate) adverse events were assessed by the Common Terminology Criteria in Adverse Events (CTCAE) v3.0 if reported prior to August 1, 2010 and CTCAE v4.0 if reported after. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
    Time Frame Approximately 6 months while on trial

    Outcome Measure Data

    Analysis Population Description
    The colorectal and non-colorectal cohorts received the same treatment on the same schedule, had no immune dysfunction at baseline and are biologically equivalent. For rare events in small cohorts, a better estimate of the true event rate is determined by grouping similar patients and is consistent with the peer-reviewed clinical paper.
    Arm/Group Title Colorectal Cancer and Non-Colorectal Cancer Cohort
    Arm/Group Description Patients with histologically confirmed measurable or evaluable metastatic colorectal cancer, non-colorectal cancer or patients with surgically resected metastatic disease at high risk for recurrence who had completed at least one 5-fluorouracil/(5-FU) containing chemotherapy regimen (e.g., 5-fluorouracil/leucovorin (5-FU/LV) with or without either irinotecan or oxaliplatin or patients that have had an elevated serum CEA (>5 ugg/L) at any point during their disease course who have failed or not a candidate for standard therapy.
    Measure Participants 25
    Measure Vaccines administered 180
    Injection-site reaction
    88
    Fatigue
    5
    Fever
    3
    Hemoglobin/Anemia
    1
    Hypoalbuminemia
    1
    Alk Phos
    1
    Syncope
    0
    Anorexia
    1
    Vomiting
    1
    Hot flushes/flashes
    1
    3. Secondary Outcome
    Title Percentage of Participants With Grade 1 and Grade 2 Adverse Events Possibly, Likely, or Definitely Related to Vaccine in the Breast Cancer and Ovarian Cancer Cohorts
    Description Vaccines were administered to participants and Grade 1 (mild) and Grade 2 (moderate) adverse events were assessed by the Common Terminology Criteria in Adverse Events (CTCAE) v3.0 if reported prior to August 1, 2010 and CTCAE v4.0 if reported after. Common Terminology Criteria in Adverse Events. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
    Time Frame Approximately 2 months while on trial

    Outcome Measure Data

    Analysis Population Description
    The breast and ovarian cohorts received the same treatment on the same schedule, had no evidence of immune dysfunction at baseline and are biologically equivalent. For rare events that occur in small trial arms, the true event rate is better determined by grouping similar patients and is consistent with the peer-reviewed clinical paper.
    Arm/Group Title Breast Cancer and Ovarian Cancer Cohorts
    Arm/Group Description Patients with evaluable, metastatic breast or ovarian cancer who have failed or not a candidate for standard therapy.
    Measure Participants 26
    Injection-site reaction
    22
    220%
    Musculoskeletal pain
    2
    20%
    Anemia
    1
    10%
    4. Secondary Outcome
    Title Number of Participants With Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE) v3.0 and v4.0
    Description Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE) v3.0 if reported prior to August 1, 2010 and CTCAE v4.0 if reported after. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
    Time Frame Date consent signed to date off study, approximately 164 months and 10 days

    Outcome Measure Data

    Analysis Population Description
    Pts in these 2 cohorts rec'd the same treatment, have absence of immune dysfunction at baseline and are biologically equivalent. For rare events that occur in small cohorts, a better est. of the true event rate can be determined by grouping the pts in the absence of a biological rationale and is consistent with the peer-reviewed clinical paper.
    Arm/Group Title Colorectal Cancer and Non-Colorectal Cancer Cohort Breast Cancer and Ovarian Cancer Cohort
    Arm/Group Description Patients with histologically confirmed measurable or evaluable metastatic colorectal cancer, non-colorectal cancer, or patients with surgically resected metastatic disease at high risk for recurrence who had completed at least one 5-fluorouracil/(5-FU) containing chemotherapy regimen (e.g., 5-fluorouracil/leucovorin (5-FU/LV) with or without either irinotecan or oxaliplatin or patients that have had an elevated serum CEA (>5 ugg/L) at any point during their disease course who have failed or not a candidate for standard therapy. Patients with evaluable, metastatic breast cancer or ovarian cancer who have failed or not a candidate for standard therapy.
    Measure Participants 25 26
    Count of Participants [Participants]
    25
    250%
    26
    173.3%
    5. Secondary Outcome
    Title Number of Participants With an Positive Immune Response to Carcinoembryonic Antigen (CEA) Peptide and/or Protein in the Colorectal Cancer and Non-colorectal Cancer Cohort Post Vaccination
    Description Immune response in human leukocyte antigens (HLA)-A2 positive patients to carcinoembryonic antigen (CEA) was assessed by enzyme-linked immunospot assay (ELISPOT) analysis. A positive immune response was defined as a >2x fold increase in the number of interferon gamma producing cells.
    Time Frame post vaccination (up to Day 84)

    Outcome Measure Data

    Analysis Population Description
    Overall number of participants analyzed reflects participants that are HLA-A2 positive.
    Arm/Group Title Colorectal Cancer Cohort Non-Colorectal Cancer Cohort
    Arm/Group Description Patients with histologically confirmed measurable or evaluable metastatic colorectal cancer or patients with surgically resected metastatic disease at high risk for recurrence who had completed at least one 5-fluorouracil/(5-FU) containing chemotherapy regimen (e.g., 5-fluorouracil/leucovorin (5-FU/LV) with or without either irinotecan or oxaliplatin or patients that have had an elevated serum CEA (>5 ugg/L) at any point during their disease course who have failed or not a candidate for standard therapy. Patients with histologically confirmed measurable or evaluable metastatic non-colorectal cancer or patients with surgically resected metastatic disease at high risk for recurrence who had completed at least one 5-fluorouracil/(5-FU) containing chemotherapy regimen (e.g., 5-fluorouracil/leucovorin (5-FU/LV) with or without either irinotecan or oxaliplatin or patients that have had an elevated serum CEA (>5 ugg/L) at any point during their disease course who have failed or not a candidate for standard therapy.
    Measure Participants 9 9
    Count of Participants [Participants]
    3
    30%
    6
    40%
    6. Secondary Outcome
    Title Number of Participants With an Positive Immune Response to Carcinoembryonic Antigen (CEA) Peptide and/or Protein in the Breast Cancer and Ovarian Cancer Cohorts Post Vaccination
    Description Immune response in human leukocyte antigens (HLA)-A2 positive patients to carcinoembryonic antigen (CEA) was assessed by enzyme-linked immunospot assay (ELISPOT) analysis. A positive immune response was defined as a >2x fold increase in the number of interferon gamma producing cells.
    Time Frame post vaccination (up to Day 84)

    Outcome Measure Data

    Analysis Population Description
    Only 3 Breast Cancer and 2 Ovarian Cancer patients had enough blood collected to perform enzyme-linked immunospot (ELISPOT) analysis.
    Arm/Group Title Breast Cancer Cohort Ovarian Cancer Cohort
    Arm/Group Description Patients with evaluable, metastatic breast cancer who have failed or not a candidate for standard therapy. Patients with evaluable, metastatic ovarian cancer who have failed or not a candidate for standard therapy.
    Measure Participants 3 2
    Count of Participants [Participants]
    1
    10%
    1
    6.7%

    Adverse Events

    Time Frame Date treatment consent signed to date off study, approximately 164 months and 10 days.
    Adverse Event Reporting Description Adverse events were assessed by the Common Terminology Criteria in Adverse Events(CTCAE)*v3.0 if reported prior to August 1, 2010 and CTCAE *v4.0 if reported after.
    Arm/Group Title Colorectal Cancer vs Non-Colorectal Cancer Cohort Breast and Ovarian Cohorts
    Arm/Group Description Patients with histologically confirmed measurable or evaluable metastatic colorectal cancer or patients with surgically resected metastatic disease at high risk for recurrence who had completed at least one 5-fluorouracil/(5-FU) containing chemotherapy regimen (e.g., 5-fluorouracil/leucovorin (5-FU/LV) with or without either irinotecan or oxaliplatin or patients that have had an elevated serum CEA (>5 ugg/L) at any point during their disease course who have failed or not a candidate for standard therapy. Patients with evaluable, metastatic breast or ovarian cancer who have failed or not a candidate for standard therapy.
    All Cause Mortality
    Colorectal Cancer vs Non-Colorectal Cancer Cohort Breast and Ovarian Cohorts
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/25 (4%) 0/26 (0%)
    Serious Adverse Events
    Colorectal Cancer vs Non-Colorectal Cancer Cohort Breast and Ovarian Cohorts
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 25/25 (100%) 26/26 (100%)
    Blood and lymphatic system disorders
    Anemia*4 0/25 (0%) 0 1/26 (3.8%) 8
    BLOOD/BONE MARROW:: Hemoglobin*3 13/25 (52%) 34 8/26 (30.8%) 14
    BLOOD/BONE MARROW:: Leukocytes (total WBC)*3 4/25 (16%) 22 1/26 (3.8%) 3
    BLOOD/BONE MARROW:: Lymphopenia*3 2/25 (8%) 6 1/26 (3.8%) 2
    BLOOD/BONE MARROW:: Neutrophils/granulocytes (ANC/AGC)*3 5/25 (20%) 13 1/26 (3.8%) 4
    BLOOD/BONE MARROW:: Platelets*3 3/25 (12%) 3 2/26 (7.7%) 2
    LYMPHATICS:: Edema: limb*3 2/25 (8%) 2 2/26 (7.7%) 2
    COAGULATION:: INR (International Normalized Ratio of prothrombin time)*3 1/25 (4%) 1 0/26 (0%) 0
    COAGULATION:: PTT (Partial Thromboplastin Time)*3 1/25 (4%) 1 0/26 (0%) 0
    LYMPHATICS:: Lymphatics - Other (Edema-Left ankle)*3 1/25 (4%) 1 0/26 (0%) 0
    Cardiac disorders
    CARDIAC ARRHYTHMIA:: Supraventricular and nodal arrhythmia:: Sinus tachycardia*3 0/25 (0%) 0 1/26 (3.8%) 1
    Sinus bradycardia*4 0/25 (0%) 0 1/26 (3.8%) 1
    CARDIAC ARRHYTHMIA:: Palpitations*3 1/25 (4%) 1 0/26 (0%) 0
    CARDIAC GENERAL:: Hypotension*3 1/25 (4%) 1 0/26 (0%) 0
    Endocrine disorders
    ENDOCRINE:: Hot flashes/flushes*3 1/25 (4%) 1 0/26 (0%) 0
    ENDOCRINE:: Thyroid function, low (hypothyroidism)*3 1/25 (4%) 1 0/26 (0%) 0
    Eye disorders
    OCULAR/VISUAL:: Keratitis (corneal inflammation/corneal ulceration)*3 1/25 (4%) 1 0/26 (0%) 0
    OCULAR/VISUAL:: Vision-blurred vision*3 1/25 (4%) 1 0/26 (0%) 0
    PAIN:: Pain:: Eye*3 1/25 (4%) 1 1/26 (3.8%) 1
    Gastrointestinal disorders
    Diarrhea*4 0/25 (0%) 0 1/26 (3.8%) 1
    GASTROINTESTINAL:: Anorexia*3 5/25 (20%) 6 2/26 (7.7%) 2
    GASTROINTESTINAL:: Constipation*3 3/25 (12%) 4 5/26 (19.2%) 6
    GASTROINTESTINAL:: Dehydration*3 4/25 (16%) 4 1/26 (3.8%) 1
    GASTROINTESTINAL:: Diarrhea*3 5/25 (20%) 8 5/26 (19.2%) 9
    GASTROINTESTINAL:: Distension/bloating, abdominal*3 2/25 (8%) 2 1/26 (3.8%) 1
    GASTROINTESTINAL:: Dysphagia (difficulty swallowing)*3 2/25 (8%) 2 1/26 (3.8%) 1
    GASTROINTESTINAL:: Heartburn/dyspepsia*3 6/25 (24%) 12 2/26 (7.7%) 3
    GASTROINTESTINAL:: Nausea*3 5/25 (20%) 12 10/26 (38.5%) 13
    GASTROINTESTINAL:: Vomiting*3 5/25 (20%) 9 5/26 (19.2%) 8
    Gingival pain*4 0/25 (0%) 0 1/26 (3.8%) 1
    PAIN:: Pain:: Throat/pharynx/larynx*3 0/25 (0%) 0 1/26 (3.8%) 1
    Vomiting*4 0/25 (0%) 0 1/26 (3.8%) 1
    GASTROINTESTINAL:: Flatulence*3 2/25 (8%) 2 0/26 (0%) 0
    GASTROINTESTINAL:: Gastrointestinal - Other (Partial bowel obstruction)*3 0/25 (0%) 0 1/26 (3.8%) 1
    GASTROINTESTINAL:: Mucositis/stomatitis (functional/symptomatic):: Oral cavity*3 1/25 (4%) 1 0/26 (0%) 0
    GASTROINTESTINAL:: Obstruction, GI:: Small bowel NOS*3 1/25 (4%) 6 0/26 (0%) 0
    GASTROINTESTINAL:: Taste alteration (dysgeusia)*3 1/25 (4%) 1 0/26 (0%) 0
    HEMORRHAGE/BLEEDING:: Hemorrhage, GI:: Lower GI NOS*3 1/25 (4%) 1 0/26 (0%) 0
    HEMORRHAGE/BLEEDING:: Hemorrhage, GI:: Rectum*3 1/25 (4%) 1 0/26 (0%) 0
    PAIN:: Pain:: Abdomen NOS*3 5/25 (20%) 9 6/26 (23.1%) 8
    PAIN:: Pain:: Oral cavity*3 1/25 (4%) 1 0/26 (0%) 0
    PAIN:: Pain:: Stomach*3 2/25 (8%) 2 1/26 (3.8%) 1
    GASTROINTESTINAL:: Gastrointestinal - Other (Emesis)*3 1/25 (4%) 1 1/26 (3.8%) 1
    GASTROINTESTINAL:: Gastrointestinal - Other (Erythema Mucosa-Under tongue & hard palate)*3 0/25 (0%) 0 1/26 (3.8%) 1
    GASTROINTESTINAL:: Gastrointestinal - Other (Gastroesophageal reflux disease )*3 0/25 (0%) 0 1/26 (3.8%) 1
    General disorders
    METABOLIC/LABORATORY:: Albumin, serum-low (hypoalbuminemia)*3 0/25 (0%) 0 1/26 (3.8%) 2
    CONSTITUTIONAL SYMPTOMS:: Weight gain*3 0/25 (0%) 0 1/26 (3.8%) 1
    Fever*4 0/25 (0%) 0 1/26 (3.8%) 1
    HEMORRHAGE/BLEEDING:: Hemorrhage/Bleeding - Other (Spotting)*3 0/25 (0%) 0 1/26 (3.8%) 1
    Injection site reaction*4 0/25 (0%) 0 1/26 (3.8%) 4
    Non-cardiac chest pain*4 0/25 (0%) 0 1/26 (3.8%) 1
    PAIN:: Pain - Other (Burning sensation waist & tumor area)*3 0/25 (0%) 0 1/26 (3.8%) 1
    Pain*4 0/25 (0%) 0 1/26 (3.8%) 4
    SYNDROMES:: Flu-like syndrome*3 3/25 (12%) 12 18/26 (69.2%) 35
    CONSTITUTIONAL SYMPTOMS:: Constitutional Symptoms - Other (Cold )*3 1/25 (4%) 1 0/26 (0%) 0
    CONSTITUTIONAL SYMPTOMS:: Fatigue (asthenia, lethargy, malaise)*3 13/25 (52%) 24 10/26 (38.5%) 20
    CONSTITUTIONAL SYMPTOMS:: Fever (in the absence of neutropenia, 10/25 (40%) 14 13/26 (50%) 18
    CONSTITUTIONAL SYMPTOMS:: Insomnia*3 1/25 (4%) 2 2/26 (7.7%) 2
    CONSTITUTIONAL SYMPTOMS:: Rigors/chills*3 12/25 (48%) 14 3/26 (11.5%) 4
    CONSTITUTIONAL SYMPTOMS:: Sweating (diaphoresis)*3 4/25 (16%) 5 2/26 (7.7%) 4
    CONSTITUTIONAL SYMPTOMS:: Weight loss*3 1/25 (4%) 1 0/26 (0%) 0
    DEATH:: Death not associated with CTCAE term:: Disease progression NOS*3 1/25 (4%) 1 1/26 (3.8%) 1
    PAIN:: Pain:: Pain NOS*3 1/25 (4%) 1 0/26 (0%) 0
    PAIN:: Pain - Other (Right inguinal pain)*3 0/25 (0%) 0 1/26 (3.8%) 1
    PAIN:: Pain - Other (Rt. thigh pain)*3 0/25 (0%) 0 1/26 (3.8%) 2
    PAIN:: Pain - Other (Sternum pain)*3 0/25 (0%) 0 1/26 (3.8%) 1
    PAIN:: Pain - Other (Pain-Upper right quadrant)*3 1/25 (4%) 1 0/26 (0%) 0
    PAIN:: Pain - Other (Rt. flank)*3 1/25 (4%) 1 0/26 (0%) 0
    PAIN:: Pain - Other (Rt. ear)*3 1/25 (4%) 1 0/26 (0%) 0
    PAIN:: Pain - Other (Pain from inserted biliary stents)*3 1/25 (4%) 1 0/26 (0%) 0
    Hepatobiliary disorders
    HEPATOBILIARY/PANCREAS:: Pancreatitis*3 1/25 (4%) 1 0/26 (0%) 0
    Immune system disorders
    Allergic reaction*4 0/25 (0%) 0 1/26 (3.8%) 1
    ALLERGY/IMMUNOLOGY:: Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)*3 2/25 (8%) 4 4/26 (15.4%) 6
    Infections and infestations
    INFECTION:: Infection - Other (Lt. lower leg, redness, swelling, & whelts)*3 0/25 (0%) 0 1/26 (3.8%) 1
    INFECTION:: Infection with normal ANC or Grade 1 or 2 neutrophils:: Lung (pneumonia)*3 0/25 (0%) 0 1/26 (3.8%) 1
    Wound infection*4 0/25 (0%) 0 1/26 (3.8%) 2
    INFECTION:: Infection with normal ANC or Grade 1 or 2 neutrophils:: Sinus*3 2/25 (8%) 2 0/26 (0%) 0
    INFECTION:: Infection with normal ANC or Grade 1 or 2 neutrophils:: Urinary tract NOS*3 2/25 (8%) 2 1/26 (3.8%) 1
    INFECTION:: Infection with unknown ANC:: Urinary tract NOS*3 1/25 (4%) 2 0/26 (0%) 0
    INFECTION:: Infection with unknown ANC:: Wound*3 1/25 (4%) 1 0/26 (0%) 0
    Injury, poisoning and procedural complications
    Bruising*4 0/25 (0%) 0 1/26 (3.8%) 1
    Fall*4 0/25 (0%) 0 1/26 (3.8%) 1
    Wound dehiscence*4 0/25 (0%) 0 1/26 (3.8%) 2
    Investigations
    Activated partial thromboplastin time prolonged*4 0/25 (0%) 0 1/26 (3.8%) 1
    Alanine aminotransferase increased*4 0/25 (0%) 0 1/26 (3.8%) 5
    Alkaline phosphatase increased*4 0/25 (0%) 0 1/26 (3.8%) 1
    Aspartate aminotransferase increased*4 0/25 (0%) 0 1/26 (3.8%) 6
    CPK increased*4 0/25 (0%) 0 1/26 (3.8%) 1
    Creatinine increased*4 0/25 (0%) 0 1/26 (3.8%) 1
    Investigations - Other, specify*4 0/25 (0%) 0 1/26 (3.8%) 1
    Lipase increased*4 0/25 (0%) 0 1/26 (3.8%) 1
    Lymphocyte count decreased*4 0/25 (0%) 0 1/26 (3.8%) 9
    Neutrophil count decreased*4 0/25 (0%) 0 1/26 (3.8%) 1
    Weight gain*4 0/25 (0%) 0 1/26 (3.8%) 2
    Metabolism and nutrition disorders
    Hyperglycemia*4 0/25 (0%) 0 1/26 (3.8%) 5
    Hypernatremia*4 0/25 (0%) 0 1/26 (3.8%) 1
    Hyperuricemia*4 0/25 (0%) 0 1/26 (3.8%) 1
    Hypoalbuminemia*4 0/25 (0%) 0 1/26 (3.8%) 3
    Hypocalcemia*4 0/25 (0%) 0 1/26 (3.8%) 3
    Hypoglycemia*4 0/25 (0%) 0 1/26 (3.8%) 1
    Hypokalemia*4 0/25 (0%) 0 1/26 (3.8%) 1
    Hypomagnesemia*4 0/25 (0%) 0 1/26 (3.8%) 4
    Hyponatremia*4 0/25 (0%) 0 1/26 (3.8%) 2
    Hypophosphatemia*4 0/25 (0%) 0 1/26 (3.8%) 5
    METABOLIC/LABORATORY:: Glucose, serum-low (hypoglycemia)*3 0/25 (0%) 0 1/26 (3.8%) 1
    METABOLIC/LABORATORY:: Hemoglobinuria*3 0/25 (0%) 0 1/26 (3.8%) 1
    METABOLIC/LABORATORY:: Sodium, serum-high (hypernatremia)*3 0/25 (0%) 0 1/26 (3.8%) 1
    METABOLIC/LABORATORY:: ALT, SGPT (serum glutamic pyruvic transaminase)*3 8/25 (32%) 18 2/26 (7.7%) 2
    METABOLIC/LABORATORY:: AST, SGOT(serum glutamic oxaloacetic transaminase)*3 7/25 (28%) 12 8/26 (30.8%) 8
    METABOLIC/LABORATORY:: Albumin, serum-low (hypoalbuminemia)*3 15/25 (60%) 26 20/26 (76.9%) 25
    METABOLIC/LABORATORY:: Alkaline phosphatase*3 8/25 (32%) 10 5/26 (19.2%) 6
    METABOLIC/LABORATORY:: Amylase*3 1/25 (4%) 2 0/26 (0%) 0
    METABOLIC/LABORATORY:: Bicarbonate, serum-low*3 2/25 (8%) 5 0/26 (0%) 0
    METABOLIC/LABORATORY:: Bilirubin (hyperbilirubinemia)*3 8/25 (32%) 12 3/26 (11.5%) 3
    METABOLIC/LABORATORY:: CPK (creatine phosphokinase)*3 2/25 (8%) 2 2/26 (7.7%) 2
    METABOLIC/LABORATORY:: Calcium, serum-high (hypercalcemia)*3 5/25 (20%) 7 0/26 (0%) 0
    METABOLIC/LABORATORY:: Calcium, serum-low (hypocalcemia)*3 5/25 (20%) 7 2/26 (7.7%) 2
    METABOLIC/LABORATORY:: Cholesterol, serum-high (hypercholesteremia)*3 1/25 (4%) 1 1/26 (3.8%) 1
    METABOLIC/LABORATORY:: Creatinine*3 1/25 (4%) 2 0/26 (0%) 0
    METABOLIC/LABORATORY:: GGT (gamma-Glutamyl transpeptidase)*3 1/25 (4%) 1 0/26 (0%) 0
    METABOLIC/LABORATORY:: Glucose, serum-high (hyperglycemia)*3 9/25 (36%) 11 5/26 (19.2%) 5
    METABOLIC/LABORATORY:: Lipase*3 1/25 (4%) 2 0/26 (0%) 0
    METABOLIC/LABORATORY:: Magnesium, serum-high (hypermagnesemia)*3 3/25 (12%) 3 1/26 (3.8%) 1
    METABOLIC/LABORATORY:: Magnesium, serum-low (hypomagnesemia)*3 4/25 (16%) 11 5/26 (19.2%) 9
    METABOLIC/LABORATORY:: Phosphate, serum-low (hypophosphatemia)*3 2/25 (8%) 2 1/26 (3.8%) 1
    METABOLIC/LABORATORY:: Potassium, serum-high (hyperkalemia)*3 2/25 (8%) 3 2/26 (7.7%) 2
    METABOLIC/LABORATORY:: Potassium, serum-low (hypokalemia)*3 2/25 (8%) 3 1/26 (3.8%) 1
    METABOLIC/LABORATORY:: Proteinuria*3 4/25 (16%) 4 2/26 (7.7%) 2
    METABOLIC/LABORATORY:: Sodium, serum-low (hyponatremia)*3 7/25 (28%) 10 4/26 (15.4%) 4
    METABOLIC/LABORATORY:: Uric acid, serum-high (hyperuricemia)*3 5/25 (20%) 14 2/26 (7.7%) 2
    Musculoskeletal and connective tissue disorders
    Back pain*4 0/25 (0%) 0 1/26 (3.8%) 1
    MUSCULOSKELETAL/SOFT TISSUE:: Muscle weakness, generalized or specific area 0/25 (0%) 0 3/26 (11.5%) 4
    Neck pain*4 0/25 (0%) 0 1/26 (3.8%) 1
    PAIN:: Pain:: Chest/thorax NOS*3 0/25 (0%) 0 1/26 (3.8%) 1
    PAIN:: Pain:: Back*3 10/25 (40%) 11 5/26 (19.2%) 6
    PAIN:: Pain:: Bone*3 3/25 (12%) 3 2/26 (7.7%) 2
    PAIN:: Pain:: Chest wall*3 1/25 (4%) 1 1/26 (3.8%) 1
    PAIN:: Pain:: Extremity-limb*3 6/25 (24%) 6 4/26 (15.4%) 4
    PAIN:: Pain:: Joint*3 4/25 (16%) 5 0/26 (0%) 0
    PAIN:: Pain:: Muscle*3 12/25 (48%) 20 4/26 (15.4%) 4
    PAIN:: Pain:: Neck*3 1/25 (4%) 2 0/26 (0%) 0
    Nervous system disorders
    Headache*4 0/25 (0%) 0 1/26 (3.8%) 1
    NEUROLOGY:: Mood alteration:: Agitation*3 0/25 (0%) 0 1/26 (3.8%) 1
    NEUROLOGY:: Neuropathy: motor*3 0/25 (0%) 0 1/26 (3.8%) 1
    Nervous system disorders - Other, specify*4 0/25 (0%) 0 1/26 (3.8%) 1
    Peripheral motor neuropathy*4 0/25 (0%) 0 1/26 (3.8%) 1
    NEUROLOGY:: Dizziness*3 5/25 (20%) 8 1/26 (3.8%) 2
    NEUROLOGY:: Mood alteration:: Anxiety*3 2/25 (8%) 2 0/26 (0%) 0
    NEUROLOGY:: Mood alteration:: Depression*3 1/25 (4%) 1 1/26 (3.8%) 1
    NEUROLOGY:: Neuropathy: cranial:: CN I Smell*3 1/25 (4%) 1 0/26 (0%) 0
    NEUROLOGY:: Neuropathy: cranial:: CN VIII Hearing and balance*3 1/25 (4%) 1 0/26 (0%) 0
    NEUROLOGY:: Syncope (fainting)*3 2/25 (8%) 2 0/26 (0%) 0
    PAIN:: Pain:: Head/headache*3 12/25 (48%) 20 11/26 (42.3%) 17
    Psychiatric disorders
    Delirium*4 0/25 (0%) 0 1/26 (3.8%) 1
    Depression*4 0/25 (0%) 0 1/26 (3.8%) 1
    Hallucinations*4 0/25 (0%) 0 1/26 (3.8%) 1
    Renal and urinary disorders
    Cystitis noninfective*4 0/25 (0%) 0 1/26 (3.8%) 1
    HEMORRHAGE/BLEEDING:: Hemorrhage, GU:: Urinary NOS*3 0/25 (0%) 0 1/26 (3.8%) 1
    Nasal congestion*4 0/25 (0%) 0 1/26 (3.8%) 1
    HEMORRHAGE/BLEEDING:: Hemorrhage, GU:: Bladder*3 1/25 (4%) 1 0/26 (0%) 0
    PAIN:: Pain:: Bladder*3 1/25 (4%) 1 0/26 (0%) 0
    RENAL/GENITOURINARY:: Bladder spasms*3 1/25 (4%) 2 0/26 (0%) 0
    RENAL/GENITOURINARY:: Renal/Genitourinary - Other (Dysuria)*3 1/25 (4%) 1 0/26 (0%) 0
    RENAL/GENITOURINARY:: Urinary frequency/urgency*3 2/25 (8%) 2 1/26 (3.8%) 1
    Reproductive system and breast disorders
    PAIN:: Pain:: Pelvis*3 0/25 (0%) 0 3/26 (11.5%) 3
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis*4 0/25 (0%) 0 1/26 (3.8%) 1
    PULMONARY/UPPER RESPIRATORY:: Nasal cavity/paranasal sinus reactions*3 0/25 (0%) 0 1/26 (3.8%) 1
    PULMONARY/UPPER RESPIRATORY:: Pleural effusion (non-malignant)*3 0/25 (0%) 0 1/26 (3.8%) 1
    Pleural effusion*4 0/25 (0%) 0 1/26 (3.8%) 1
    HEMORRHAGE/BLEEDING:: Hemorrhage, pulmonary/upper respiratory:: Nose*3 1/25 (4%) 1 0/26 (0%) 0
    PULMONARY/UPPER RESPIRATORY:: Bronchospasm, wheezing*3 1/25 (4%) 1 0/26 (0%) 0
    PULMONARY/UPPER RESPIRATORY:: Cough*3 5/25 (20%) 6 7/26 (26.9%) 9
    PULMONARY/UPPER RESPIRATORY:: Dyspnea (shortness of breath)*3 1/25 (4%) 1 2/26 (7.7%) 3
    Skin and subcutaneous tissue disorders
    DERMATOLOGY/SKIN:: Dermatology/Skin - Other (Allergic reaction-Tape)*3 0/25 (0%) 0 1/26 (3.8%) 1
    DERMATOLOGY/SKIN:: Dry skin*3 0/25 (0%) 0 2/26 (7.7%) 2
    DERMATOLOGY/SKIN:: Injection site reaction/extravasation changes*3 0/25 (0%) 0 23/26 (88.5%) 83
    Pruritus*4 0/25 (0%) 0 1/26 (3.8%) 1
    DERMATOLOGY/SKIN:: Bruising (in absence of Grade 3 or 4 thrombocytopenia)*3 1/25 (4%) 2 0/26 (0%) 0
    DERMATOLOGY/SKIN:: Induration/fibrosis (skin and subcutaneous tissue)*3 1/25 (4%) 1 0/26 (0%) 0
    DERMATOLOGY/SKIN:: Injection site reaction/extravasation changes*3 25/25 (100%) 146 23/26 (88.5%) 83
    DERMATOLOGY/SKIN:: Nail changes*3 1/25 (4%) 1 5/26 (19.2%) 5
    DERMATOLOGY/SKIN:: Pruritus/itching*3 1/25 (4%) 1 0/26 (0%) 0
    DERMATOLOGY/SKIN:: Rash/desquamation*3 2/25 (8%) 4 1/26 (3.8%) 1
    Dermatology/Skin - Other (Mouth sore-lower lip)*3 0/25 (0%) 0 1/26 (3.8%) 1
    Surgical and medical procedures
    Surgical and medical procedures - Other, specify*4 0/25 (0%) 0 1/26 (3.8%) 1
    Other (Not Including Serious) Adverse Events
    Colorectal Cancer vs Non-Colorectal Cancer Cohort Breast and Ovarian Cohorts
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 25/25 (100%) 26/26 (100%)
    Blood and lymphatic system disorders
    Anemia*4 0/25 (0%) 0 1/26 (3.8%) 1
    BLOOD/BONE MARROW:: Hemoglobin*3 13/25 (52%) 34 1/26 (3.8%) 1
    BLOOD/BONE MARROW:: Leukocytes (total WBC)*3 4/25 (16%) 22 8/26 (30.8%) 14
    BLOOD/BONE MARROW:: Lymphopenia*3 2/25 (8%) 6 1/26 (3.8%) 3
    BLOOD/BONE MARROW:: Neutrophils/granulocytes (ANC/AGC)*3 5/25 (20%) 13 1/26 (3.8%) 2
    BLOOD/BONE MARROW:: Platelets*3 3/25 (12%) 3 1/26 (3.8%) 4
    LYMPHATICS:: Edema: limb*3 2/25 (8%) 2 1/26 (3.8%) 4
    COAGULATION:: INR (International Normalized Ratio of prothrombin time)*3 1/25 (4%) 1 0/26 (0%) 0
    COAGULATION:: PTT (Partial Thromboplastin Time)*3 1/25 (4%) 1 0/26 (0%) 0
    LYMPHATICS:: Lymphatics - Other (Edema-left ankle)*3 1/25 (4%) 1 0/26 (0%) 0
    Cardiac disorders
    CARDIAC ARRHYTHMIA:: Supraventricular and nodal arrhythmia:: Sinus tachycardia*3 0/25 (0%) 0 1/26 (3.8%) 1
    Sinus bradycardia*4 0/25 (0%) 0 18/26 (69.2%) 35
    CARDIAC ARRHYTHMIA:: Palpitations*3 1/25 (4%) 1 0/26 (0%) 0
    CARDIAC GENERAL:: Hypotension*3 1/25 (4%) 1 0/26 (0%) 0
    Endocrine disorders
    ENDOCRINE:: Hot flashes/flushes*3 1/25 (4%) 1 0/26 (0%) 0
    ENDOCRINE:: Thyroid function, low (hypothyroidism)*3 1/25 (4%) 1 0/26 (0%) 0
    Eye disorders
    PAIN:: Pain:: Eye*3 1/25 (4%) 1 4/26 (15.4%) 4
    Eye disorders - Other, specify 0/25 (0%) 0 1/26 (3.8%) 1
    OCULAR/VISUAL:: Keratitis (corneal inflammation/corneal ulceration)*3 1/25 (4%) 1 0/26 (0%) 0
    OCULAR/VISUAL:: Vision-blurred vision*3 1/25 (4%) 1 0/26 (0%) 0
    Gastrointestinal disorders
    Diarrhea*4 0/25 (0%) 0 1/26 (3.8%) 1
    GASTROINTESTINAL:: Anorexia*3 5/25 (20%) 6 1/26 (3.8%) 1
    GASTROINTESTINAL:: Constipation*3 3/25 (12%) 4 2/26 (7.7%) 2
    GASTROINTESTINAL:: Diarrhea*3 5/25 (20%) 8 5/26 (19.2%) 6
    GASTROINTESTINAL:: Distension/bloating, abdominal*3 2/25 (8%) 2 5/26 (19.2%) 9
    GASTROINTESTINAL:: Dysphagia (difficulty swallowing)*3 2/25 (8%) 2 1/26 (3.8%) 1
    GASTROINTESTINAL:: Heartburn/dyspepsia*3 6/25 (24%) 12 4/26 (15.4%) 4
    GASTROINTESTINAL:: Nausea*3 5/25 (20%) 12 2/26 (7.7%) 3
    GASTROINTESTINAL:: Vomiting*3 5/25 (20%) 9 10/26 (38.5%) 13
    Gingival pain*4 0/25 (0%) 0 5/26 (19.2%) 8
    PAIN:: Pain:: Abdomen NOS*3 5/25 (20%) 9 3/26 (11.5%) 5
    PAIN:: Pain:: Stomach*3 2/25 (8%) 2 3/26 (11.5%) 3
    Vomiting*4 0/25 (0%) 0 1/26 (3.8%) 1
    GASTROINTESTINAL:: Dehydration*3 3/25 (12%) 3 0/26 (0%) 0
    GASTROINTESTINAL:: Flatulence*3 2/25 (8%) 2 0/26 (0%) 0
    GASTROINTESTINAL:: Mucositis/stomatitis (functional/symptomatic):: Oral cavity*3 1/25 (4%) 1 0/26 (0%) 0
    GASTROINTESTINAL:: Obstruction, GI:: Small bowel NOS*3 1/25 (4%) 2 0/26 (0%) 0
    GASTROINTESTINAL:: Taste alteration (dysgeusia)*3 1/25 (4%) 1 0/26 (0%) 0
    HEMORRHAGE/BLEEDING:: Hemorrhage, GI:: Lower GI NOS*3 1/25 (4%) 1 0/26 (0%) 0
    HEMORRHAGE/BLEEDING:: Hemorrhage, GI:: Rectum*3 1/25 (4%) 1 0/26 (0%) 0
    PAIN:: Pain:: Oral cavity*3 1/25 (4%) 1 0/26 (0%) 0
    GASTROINTESTINAL:: Gastrointestinal - Other (Emesis)*3 1/25 (4%) 1 1/26 (3.8%) 1
    GASTROINTESTINAL:: Gastrointestinal - Other (Erythema mucosa-under tongue & hard palate )*3 0/25 (0%) 0 1/26 (3.8%) 1
    GASTROINTESTINAL:: Gastrointestinal - Other (Gastroesophageal reflux disease)*3 0/25 (0%) 0 1/26 (3.8%) 1
    GASTROINTESTINAL:: Gastrointestinal - Other (Partial bowel obstruction)*3 0/25 (0%) 0 1/26 (3.8%) 1
    General disorders
    CONSTITUTIONAL SYMPTOMS:: Fatigue (asthenia, lethargy, malaise)*3 13/25 (52%) 24 1/26 (3.8%) 1
    CONSTITUTIONAL SYMPTOMS 0/25 (0%) 0 10/26 (38.5%) 20
    CONSTITUTIONAL SYMPTOMS:: Insomnia*3 1/25 (4%) 2 13/26 (50%) 18
    CONSTITUTIONAL SYMPTOMS:: Rigors/chills*3 12/25 (48%) 14 2/26 (7.7%) 2
    CONSTITUTIONAL SYMPTOMS:: Sweating (diaphoresis)*3 4/25 (16%) 5 3/26 (11.5%) 4
    CONSTITUTIONAL SYMPTOMS:: Weight gain*3 0/25 (0%) 0 2/26 (7.7%) 4
    Fever*4 0/25 (0%) 0 1/26 (3.8%) 1
    HEMORRHAGE/BLEEDING:: Hemorrhage/Bleeding - Other (Spotting )*3 0/25 (0%) 0 1/26 (3.8%) 1
    Injection site reaction*4 0/25 (0%) 0 1/26 (3.8%) 1
    Non-cardiac chest pain*4 0/25 (0%) 0 1/26 (3.8%) 1
    PAIN:: Pain - Other (Burning sensation waist & tumor area)*3 0/25 (0%) 0 1/26 (3.8%) 1
    Pain*4 0/25 (0%) 0 1/26 (3.8%) 1
    SYNDROMES:: Flu-like syndrome*3 3/25 (12%) 12 1/26 (3.8%) 1
    CONSTITUTIONAL SYMPTOMS:: Constitutional Symptoms - Other (Cold)*3 1/25 (4%) 1 0/26 (0%) 0
    CONSTITUTIONAL SYMPTOMS:: Fever (in the absence of neutropenia, where neutropenia is defined as ANC 10/25 (40%) 14 0/26 (0%) 0
    CONSTITUTIONAL SYMPTOMS:: Weight loss*3 1/25 (4%) 1 0/26 (0%) 0
    PAIN:: Pain - Other (Pain-upper right quadrant)*3 1/25 (4%) 1 0/26 (0%) 0
    PAIN:: Pain:: Joint*3 4/25 (16%) 5 0/26 (0%) 0
    PAIN:: Pain:: Pain NOS*3 1/25 (4%) 1 0/26 (0%) 0
    PAIN:: Pain - Other (Right inguinal pain)*3 0/25 (0%) 0 1/26 (3.8%) 1
    PAIN:: Pain - Other (Rt. thigh pain)*3 0/25 (0%) 0 1/26 (3.8%) 2
    PAIN:: Pain - Other (Sternum pain)*3 0/25 (0%) 0 1/26 (3.8%) 1
    PAIN:: Pain - Other (Rt. flank)*3 1/25 (4%) 1 0/26 (0%) 0
    PAIN:: Pain - Other (Rt. ear)*3 1/25 (4%) 1 0/26 (0%) 0
    PAIN:: Pain - Other (Pain from inserted biliary stents)*3 1/25 (4%) 1 0/26 (0%) 0
    Immune system disorders
    ALLERGY/IMMUNOLOGY:: Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)*3 2/25 (8%) 4 1/26 (3.8%) 2
    Allergic reaction*4 0/25 (0%) 0 1/26 (3.8%) 1
    Infections and infestations
    INFECTION:: Infection - Other (Lt. lower leg, redness, swelling & whelts)*3 0/25 (0%) 0 1/26 (3.8%) 1
    INFECTION:: Infection with normal ANC or Grade 1 or 2 neutrophils:: Lung (pneumonia)*3 0/25 (0%) 0 1/26 (3.8%) 1
    INFECTION:: Infection with normal ANC or Grade 1 or 2 neutrophils:: Urinary tract NOS*3 2/25 (8%) 2 1/26 (3.8%) 1
    Lipase increased*4 0/25 (0%) 0 2/26 (7.7%) 2
    Wound infection*4 0/25 (0%) 0 1/26 (3.8%) 1
    INFECTION:: Infection with normal ANC or Grade 1 or 2 neutrophils:: Sinus*3 2/25 (8%) 2 0/26 (0%) 0
    INFECTION:: Infection with unknown ANC:: Urinary tract NOS*3 1/25 (4%) 2 0/26 (0%) 0
    Injury, poisoning and procedural complications
    Bruising*4 0/25 (0%) 0 1/26 (3.8%) 1
    Fall*4 0/25 (0%) 0 1/26 (3.8%) 1
    Wound dehiscence*4 0/25 (0%) 0 1/26 (3.8%) 2
    Investigations
    Activated partial thromboplastin time prolonged*4 0/25 (0%) 0 4/26 (15.4%) 6
    Alanine aminotransferase increased*4 0/25 (0%) 0 1/26 (3.8%) 1
    Alkaline phosphatase increased*4 0/25 (0%) 0 1/26 (3.8%) 1
    Aspartate aminotransferase increased*4 0/25 (0%) 0 1/26 (3.8%) 6
    CPK increased*4 0/25 (0%) 0 1/26 (3.8%) 1
    Creatinine increased*4 0/25 (0%) 0 1/26 (3.8%) 1
    Lymphocyte count decreased*4 0/25 (0%) 0 1/26 (3.8%) 1
    Neutrophil count decreased*4 0/25 (0%) 0 1/26 (3.8%) 1
    Weight gain*4 0/25 (0%) 0 1/26 (3.8%) 1
    Metabolism and nutrition disorders
    Hyperglycemia*4 0/25 (0%) 0 1/26 (3.8%) 1
    Hyperuricemia*4 0/25 (0%) 0 1/26 (3.8%) 5
    Hypoalbuminemia*4 0/25 (0%) 0 1/26 (3.8%) 1
    Hypoglycemia*4 0/25 (0%) 0 1/26 (3.8%) 2
    Hypomagnesemia*4 0/25 (0%) 0 1/26 (3.8%) 1
    Hypophosphatemia*4 0/25 (0%) 0 1/26 (3.8%) 4
    METABOLIC/LABORATORY:: ALT, SGPT (serum glutamic pyruvic transaminase)*3 8/25 (32%) 18 1/26 (3.8%) 9
    METABOLIC/LABORATORY:: AST, SGOT(serum glutamic oxaloacetic transaminase)*3 7/25 (28%) 12 2/26 (7.7%) 2
    METABOLIC/LABORATORY:: Albumin, serum-low (hypoalbuminemia)*3 15/25 (60%) 26 8/26 (30.8%) 8
    METABOLIC/LABORATORY:: Alkaline phosphatase*3 8/25 (32%) 10 20/26 (76.9%) 25
    METABOLIC/LABORATORY:: Bilirubin (hyperbilirubinemia)*3 8/25 (32%) 12 5/26 (19.2%) 6
    METABOLIC/LABORATORY:: CPK (creatine phosphokinase)*3 2/25 (8%) 2 3/26 (11.5%) 3
    METABOLIC/LABORATORY:: Calcium, serum-high (hypercalcemia)*3 5/25 (20%) 7 2/26 (7.7%) 2
    METABOLIC/LABORATORY:: Calcium, serum-low (hypocalcemia)*3 3/25 (12%) 7 2/26 (7.7%) 2
    METABOLIC/LABORATORY:: Cholesterol, serum-high (hypercholesteremia)*3 1/25 (4%) 1 1/26 (3.8%) 1
    METABOLIC/LABORATORY:: Glucose, serum-high (hyperglycemia)*3 9/25 (36%) 11 1/26 (3.8%) 1
    METABOLIC/LABORATORY:: Glucose, serum-low (hypoglycemia)*3 0/25 (0%) 0 5/26 (19.2%) 5
    METABOLIC/LABORATORY:: Hemoglobinuria*3 0/25 (0%) 0 1/26 (3.8%) 1
    METABOLIC/LABORATORY:: Magnesium, serum-high (hypermagnesemia)*3 3/25 (12%) 3 1/26 (3.8%) 1
    METABOLIC/LABORATORY:: Magnesium, serum-low (hypomagnesemia)*3 4/25 (16%) 11 1/26 (3.8%) 1
    METABOLIC/LABORATORY:: Phosphate, serum-low (hypophosphatemia)*3 2/25 (8%) 2 5/26 (19.2%) 9
    METABOLIC/LABORATORY:: Potassium, serum-high (hyperkalemia)*3 2/25 (8%) 3 1/26 (3.8%) 1
    METABOLIC/LABORATORY:: Potassium, serum-low (hypokalemia)*3 2/25 (8%) 3 2/26 (7.7%) 2
    METABOLIC/LABORATORY:: Proteinuria*3 4/25 (16%) 4 1/26 (3.8%) 1
    METABOLIC/LABORATORY:: Sodium, serum-high (hypernatremia)*3 0/25 (0%) 0 2/26 (7.7%) 2
    METABOLIC/LABORATORY:: Sodium, serum-low (hyponatremia)*3 7/25 (28%) 10 1/26 (3.8%) 1
    METABOLIC/LABORATORY:: Uric acid, serum-high (hyperuricemia)*3 5/25 (20%) 14 4/26 (15.4%) 4
    MUSCULOSKELETAL/SOFT TISSUE 0/25 (0%) 0 2/26 (7.7%) 2
    METABOLIC/LABORATORY:: Amylase*3 1/25 (4%) 2 0/26 (0%) 0
    METABOLIC/LABORATORY:: Bicarbonate, serum-low*3 2/25 (8%) 5 0/26 (0%) 0
    METABOLIC/LABORATORY:: Creatinine*3 1/25 (4%) 2 0/26 (0%) 0
    METABOLIC/LABORATORY:: GGT (gamma-Glutamyl transpeptidase)*3 1/25 (4%) 1 0/26 (0%) 0
    METABOLIC/LABORATORY:: Lipase*3 1/25 (4%) 2 0/26 (0%) 0
    Musculoskeletal and connective tissue disorders
    Back pain*4 0/25 (0%) 0 2/26 (7.7%) 2
    Neck pain*4 0/25 (0%) 0 1/26 (3.8%) 1
    PAIN:: Pain:: Back*3 10/25 (40%) 11 6/26 (23.1%) 8
    PAIN:: Pain:: Bone*3 3/25 (12%) 3 5/26 (19.2%) 6
    PAIN:: Pain:: Chest wall*3 1/25 (4%) 1 2/26 (7.7%) 2
    PAIN:: Pain:: Chest/thorax NOS*3 0/25 (0%) 0 1/26 (3.8%) 1
    PAIN:: Pain:: Extremity-limb*3 6/25 (24%) 6 1/26 (3.8%) 1
    PAIN:: Pain:: Muscle*3 12/25 (48%) 20 11/26 (42.3%) 17
    PAIN:: Pain:: Neck*3 1/25 (4%) 2 0/26 (0%) 0
    Nervous system disorders
    Headache*4 0/25 (0%) 0 1/26 (3.8%) 1
    NEUROLOGY:: Dizziness*3 5/25 (20%) 8 3/26 (11.5%) 4
    NEUROLOGY:: Mood alteration:: Agitation*3 0/25 (0%) 0 1/26 (3.8%) 2
    NEUROLOGY:: Mood alteration:: Depression*3 1/25 (4%) 1 1/26 (3.8%) 1
    NEUROLOGY:: Neuropathy: motor*3 0/25 (0%) 0 1/26 (3.8%) 1
    Nervous system disorders - Other, specify*4 0/25 (0%) 0 1/26 (3.8%) 1
    PAIN:: Pain:: Head/headache*3 12/25 (48%) 20 1/26 (3.8%) 1
    Peripheral motor neuropathy*4 0/25 (0%) 0 1/26 (3.8%) 2
    NEUROLOGY:: Mood alteration:: Anxiety*3 2/25 (8%) 2 0/26 (0%) 0
    NEUROLOGY:: Neuropathy: cranial:: CN I Smell*3 1/25 (4%) 1 0/26 (0%) 0
    NEUROLOGY:: Neuropathy: cranial:: CN VIII Hearing and balance*3 1/25 (4%) 1 0/26 (0%) 0
    NEUROLOGY:: Syncope (fainting)*3 2/25 (8%) 2 0/26 (0%) 0
    Psychiatric disorders
    Delirium*4 0/25 (0%) 0 1/26 (3.8%) 1
    Depression*4 0/25 (0%) 0 1/26 (3.8%) 1
    Hallucinations*4 0/25 (0%) 0 1/26 (3.8%) 1
    Renal and urinary disorders
    Cystitis noninfective*4 0/25 (0%) 0 1/26 (3.8%) 1
    HEMORRHAGE/BLEEDING:: Hemorrhage, GU:: Urinary NOS*3 0/25 (0%) 0 1/26 (3.8%) 1
    RENAL/GENITOURINARY:: Urinary frequency/urgency*3 2/25 (8%) 2 1/26 (3.8%) 1
    HEMORRHAGE/BLEEDING:: Hemorrhage, GU:: Bladder*3 1/25 (4%) 1 0/26 (0%) 0
    PAIN:: Pain:: Bladder*3 1/25 (4%) 1 0/26 (0%) 0
    RENAL/GENITOURINARY:: Bladder spasms*3 1/25 (4%) 2 0/26 (0%) 0
    RENAL/GENITOURINARY:: Renal/Genitourinary - Other (Dysuria)*3 1/25 (4%) 1 0/26 (0%) 0
    Reproductive system and breast disorders
    PAIN:: Pain:: Pelvis*3 0/25 (0%) 0 4/26 (15.4%) 4
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis*4 0/25 (0%) 0 1/26 (3.8%) 1
    Nasal congestion*4 0/25 (0%) 0 1/26 (3.8%) 1
    PAIN:: Pain:: Throat/pharynx/larynx*3 0/25 (0%) 0 1/26 (3.8%) 1
    PULMONARY/UPPER RESPIRATORY:: Cough*3 5/25 (20%) 6 1/26 (3.8%) 1
    PULMONARY/UPPER RESPIRATORY:: Dyspnea (shortness of breath)*3 1/25 (4%) 1 7/26 (26.9%) 9
    PULMONARY/UPPER RESPIRATORY:: Nasal cavity/paranasal sinus reactions*3 0/25 (0%) 0 1/26 (3.8%) 1
    HEMORRHAGE/BLEEDING:: Hemorrhage, pulmonary/upper respiratory:: Nose*3 1/25 (4%) 1 0/26 (0%) 0
    PULMONARY/UPPER RESPIRATORY:: Bronchospasm, wheezing*3 1/25 (4%) 1 0/26 (0%) 0
    Skin and subcutaneous tissue disorders
    DERMATOLOGY/SKIN:: Dermatology/Skin - Other (Allergic reaction-Tape )*3 0/25 (0%) 0 1/26 (3.8%) 1
    DERMATOLOGY/SKIN:: Dry skin*3 0/25 (0%) 0 1/26 (3.8%) 2
    DERMATOLOGY/SKIN:: Injection site reaction/extravasation changes*3 25/25 (100%) 146 2/26 (7.7%) 2
    DERMATOLOGY/SKIN:: Pruritus/itching*3 1/25 (4%) 1 23/26 (88.5%) 83
    DERMATOLOGY/SKIN:: Rash/desquamation*3 2/25 (8%) 4 5/26 (19.2%) 5
    Pruritus*4 0/25 (0%) 0 1/26 (3.8%) 1
    DERMATOLOGY/SKIN:: Bruising (in absence of Grade 3 or 4 thrombocytopenia)*3 1/25 (4%) 2 0/26 (0%) 0
    DERMATOLOGY/SKIN:: Induration/fibrosis (skin and subcutaneous tissue)*3 1/25 (4%) 1 0/26 (0%) 0
    DERMATOLOGY/SKIN:: Nail changes*3 1/25 (4%) 1 0/26 (0%) 0
    DERMATOLOGY/SKIN:: Dermatology/Skin - Other (Mouth sore-lower lip)*3 0/25 (0%) 0 1/26 (3.8%) 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.

    Results Point of Contact

    Name/Title Dr. James Gulley
    Organization National Cancer Institute
    Phone 301-480-8870
    Email james_gulley@nih.gov
    Responsible Party:
    James Gulley, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC)
    ClinicalTrials.gov Identifier:
    NCT00088413
    Other Study ID Numbers:
    • 040246
    • 04-C-0246
    • NCT00091000
    First Posted:
    Jul 26, 2004
    Last Update Posted:
    Apr 16, 2019
    Last Verified:
    Apr 1, 2019