Paclitaxel and CBT-1(Registered Trademark) to Treat Solid Tumors

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00972205
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arm: 1
• Duration (Months): 18
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

Background:

• Some cancer cells have a large amount of a protein called P-glycoprotein, which can pump certain chemotherapy drugs out of their cells. This pump may be part of the reason why it is difficult to shrink some cancers with chemotherapy.

• In laboratory experiments, the drug CBT-1(Registered Trademark) blocked the P-glycoprotein pump, resulting in accumulation of higher amounts of chemotherapy inside the cancer cells, making the chemotherapy more effective.

• Paclitaxel is a cancer drug that has caused tumors to shrink in many types of cancers, including lung, ovarian, breast, renal, cervical and others.

Objectives:

• To determine whether CBT-1(Registered Trademark) can block the P-glycoprotein pump on cancer cells and whether it inhibits the action of the pump found in normal blood cells and liver tissue.

• To evaluate the effectiveness of combination therapy using CBT-1(Registered Trademark) and paclitaxel in treating solid tumors and to determine whether the two drugs together are more effective than paclitaxel alone.

Eligibility:

-Patients over 18 years of age who have a solid tumor that cannot be treated successfully with standard treatments.

Design:

-Patients receive CBT-1(Registered Trademark) and paclitaxel in 21-day cycles. Treatment continues for two cycles after all the cancer is gone, or until it is decided to surgically remove some or all of the remaining cancer, or until the cancer has grown to the point where it defined as progressive disease.

For each cycle, patients take CBT-1(Registered Trademark) by mouth in three divided doses daily for 7 days. On day 6, paclitaxel is given through a vein over 3 hours.

Blood tests are done before starting CBT-1(Registered Trademark) and repeated periodically throughout treatment.

Imaging studies computed tomography or magnetic resonance imaging (CT or MRI) are done every two cycles. In addition, for the first cycle only, patients undergo imaging of tumors and normal tissue with a 99mTc-sestamibi radionuclide scan before and after administration of CBT-1(Registered Trademark). This scan helps show how well the P-glycoprotein pump is being blocked by the treatment.

Condition or Disease	Intervention/Treatment	Phase
Cervical; Ovarian; Lung; Breast; Renal	Drug: paclitaxel; Drug: CBT-1(Registered Trademark); Radiation: Tc 99m sestamibi	N/A

Detailed Description

Background:

This is a pharmacodynamic study aimed at evaluating the efficacy of CBT-1(Registered Trademark) as a modulator of Pgp-mediated drug efflux in patient tumors and normal tissues. The study will build on over a decade of experience with 99mTc-sestamibi imaging and rhodamine accumulation and efflux in normal circulating CD56 plus cells as surrogates for Pgp function. CBA Research, Inc., has carried out Phase I and II testing of CBT-1(Registered Trademark) as a drug resistance reversal agent, but has not yet confirmed that the inhibitor is able to block drug efflux.

Objectives:

Evaluate the impact of CBT-1(Registered Trademark) on the hepatic accumulation and retention of 99mTc-sestamibi in patients with relapsed or refractory solid tumor malignancies.

Evaluate the impact of CBT-1(Registered Trademark) on P-glycoprotein-mediated efflux from CD56 plus peripheral mononuclear cells.

Eligibility:

Patients over 18 years of age who have histologic confirmation of relapsed/refractory cancer, following at least once standard treatment regimen, for whom there is no known standard therapy option capable of extending life expectancy. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or better, and have hematologic, renal, hepatic, and metabolic parameters suggestive of adequate organ function.

Design:

Patients will be treated according to CBA Research Phase II trial of CBT-1 and Taxol. Patients will begin protocol treatment with orally administered CBT-1(Registered Trademark) in two or three divided doses daily for 7 days. On day 6, 135 mg/m^2 paclitaxel will be administered by intravenous infusion over 3 hours. Prior to the initiation of CBT-1(Registered Trademark), and on Day 6, patients will undergo blood sampling for the rhodamine assay in CD56 plus circulating mononuclear cells. In addition, patients will undergo imaging of tumors and normal tissue with the 99mTc-sestamibi radionuclide scan. These two assays have shown convincing inhibition of Pgp-mediated drug efflux in past studies with Pgp inhibitors such as tariquidar and valspodar. Twelve patients are planned for enrollment to this study, which is powered to determine a difference between the control scan and the post-treatment scan but not to compare CBT-1(Registered Trademark) with previous inhibitors tested in the intramural program.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pharmacodynamic Study of the P-glycoprotein (Pgp) Antagonist, CBT-1(Registered Trademark), Evaluating Pgp Inhibition in Tumors and Normal Tissues
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Paclitaxel and CBT-1

Drug: paclitaxel; Paclitaxel 135 mg/m^2 intravenously on day 6 over 180 minutes. Cycles are repeated every 21 days.; Other Names: Taxol Onxal ; Drug: CBT-1(Registered Trademark); CBT-1 500 mg/m^2 oral dose daily for 7 days in divided doses 3 times a day. Cycle days 1-7, repeated every 21 days. no antacids, H2 blocker, or gastric acid inhibiting agents will be administered within 4 hours before or after each daily dose.; Radiation: Tc 99m sestamibi; 20 mCI baseline scan day 0; 20 mCI scan on 6th day of CBT-1 administered.

Outcome Measures

Primary Outcome Measures

1. Percent Increase in Sestamibi Retention in the Liver as a Measure of P-glycoprotein Inhibition [sestamibi scanning was performed on day 0 and day 6, allowing scans to be performed pre and post CBT-1 administration]

   An area under the concentration curve (AUC) was calculated for 99mTc counts over the liver, lungs, and heart. An equation was applied to determine the increase in sestamibi in the liver: [(AUCpost - AUC baseline)/(AUC baseline)] x 100.

2. Number of Participants With Adverse Events [18 months]

   Here are the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.

Secondary Outcome Measures

1. Percent Inhibition of Rhodamine Efflux From CD56+Cells Post Treatment [Rhodamine efflux was performed on blood drawn prior to CBT-1 ingestion and after 6 days of dosing.]

   Rhodamine 123 was added to whole blood obtained before and after CBT-1. The blood was incubated, layered on lymphocyte separation medium and centrifuged. Peripheral blood mononuclear cells(PBMCs)were isolated, washed and incubated in rhodamine-free medium with or without valspodar. Cells were washed and incubated in phycoerythrin-labeled anti-CD56 antibody or negative control antibody. Rhodamine 123 fluorescence was assessed in CD56+cells with or without valspodar and a 60 min efflux period,continuing the cells without or with valspodar to generate Efflux and PSC/Efflux histograms.

2. Number of Participants Who Had an Overall Response [Baseline to progression]

   Response is determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Complete response (CR)-disappearance of all target lesions, Partial response (PR)-at least a 30% decrease in the sum of the longest diameter(LD)of target lesions, stable disease (SD) - neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. See the Protocol Link module for further details about the RECIST Criteria.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• INCLUSION CRITERIA:

Patients must fulfill all of the following criteria to be eligible for study admission:

1. Age greater than 18 years.

2. Histologic or cytologic confirmation at National Cancer Institute (NCI) Laboratory of Pathology, of recurrent or refractory, or advanced metastatic cancer of the gastrointestinal tract, breast, Taxol (Trademark) naive breast cancer, small cell lung, ovarian, prostate, head and neck, multiple myeloma, non-small cell lung cancer, Taxol (Trademark) naive non-small cell lung cancer.

3. Performance status of Eastern Cooperative Oncology Group (ECOG) 0-2.

4. Life expectancy of 3 months or greater.

5. Patient must have adequate hematologic, renal, hepatic, and metabolic functions as defined: platelet count greater than 100,000 /mL, absolute granulocyte count (AGC) greater than 1500/mL, serum creatinine less than 2.0 mg/dl (or if greater than 2.0, a measured 24 hour creatinine clearance greater than 50 mL/min), serum glutamic oxaloacetic transaminase (SGOT) 4 times institutional upper limit of normal, bilirubin 2.0 mg/dl, prothrombin time (PT) less than 1.5 times institutional upper limit of normal, partial thromboplastin time (PTT) less than 1.5 times institutional upper limit of normal, calcium less than 5.3mEq/L, albumin greater than 2.0 g/dl.

6. Electrocardiogram (EKG) showing, at most, minor abnormalities that in the judgment of the protocol chairman would not compromise the patient's ability to tolerate therapy.

7. Patients must be greater than 4 weeks from prior radiation or chemotherapy; greater than 2 weeks from hormonal or immunotherapy; greater than 4 weeks from prior experimental therapy; greater than 6 weeks from mitomycin; and greater than 8 weeks from prior UCN01 treatment. Patients receiving dexamethasone as a pretreatment for anaphylactic reactions to Taxol (Trademark) or the cremophor vehicle will not be excluded from this study.

8. No serious intercurrent medical illness or serious infection that requires parenteral antibiotics.

9. Measurable disease by radiographic means or physical examination.

10. Willingness to sign a written informed consent.

11. Patients must agree to an effective method of contraception for the study (abstinence, hormonal or barrier method of birth control, or condom) for the study and 30 days after completion of protocol.

EXCLUSION CRITERIA:

The following patient populations are not eligible for study:

1. Women of childbearing potential and potentially fertile men will be excluded unless using an effective contraception (ie. a barrier intrauterine device (IUD), birth control pill, or condom), during the treatment. Women who are pregnant or nursing will also be excluded.

2. Patients with significant intercurrent disease.

3. Human Immunodeficiencey virus (HIV) seropositive patients. Note: There may be an impact of CBT-1 on the pharmacokinetics of the drugs used in the therapy of HIV.

4. Ongoing serious infections that require parenteral antibiotics.

5. Patients with significant central nervous system (CNS) disease, including a history of seizures within the last 3 months or psychiatric history which would impair the ability to give informed consent or prevent compliance with protocol requirements.

6. Patients must not be eligible for surgery, or radiotherapy that is of known benefit to them, in terms of extension of survival. Patients with tumors sensitive to potentially curative chemotherapy must have failed such chemotherapy. Patients who have received radiation therapy may participate in this study one week after the conclusion of radiation therapy provided that the lesion being irradiated is not one that is being used to assess the efficacy of CBT-1 plus Taxol.

7. History of significant coronary artery disease, cardiac arrhythmias requiring treatment, or history of other cardiac disease that in the judgment of the investigators, would compromise the patient's ability to tolerate the therapy.

8. Patients with active bleeding due to peptic ulcer disease.

9. History of anaphylactic reactions to paclitaxel or cremophor despite adequate premedication.

10. Clinically significant bleeding disorders.

11. Patients with solid organ allografts.

12. Patients on daily gastric acid secretion inhibitors.

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: Susan S Bates, M.D., National Cancer Institute, National Institutes of Health

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page
• Medline Plus
• Drug Information
• US FDA Resources
• RECIST Criteria

Publications

None provided.

• Responsible Party: Susan Bates, Dr. Susan Bates, National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00972205
• Other Study ID Numbers: 080035; 08-C-0035; NCT00658424
• First Posted: Sep 4, 2009
• Last Update Posted: Jul 19, 2012
• Last Verified: Jul 1, 2012

• Keywords provided by Susan Bates, Dr. Susan Bates, National Cancer Institute (NCI): Pgp; Solid Tumors; Drug Resistance; Sestamibi; Cancer; Solid Tumor
• Additional relevant MeSH terms: Paclitaxel; Technetium Tc 99m Sestamibi

Study Results

Participant Flow

Arm/Group Title	Paclitaxel and CBT-1 to Treat Solid Tumors
Arm/Group Description	Patients will be treated with oral CBT-1 at a dose of 500 mg/m^2 daily for 7 days in divided doses and repeated every 21 days for 7 days beginning with cycle 1 of each cycle provided cycles are not delayed. Paclitaxel will be 135 mg/m^2 intravenously on day 6 over 180 minutes. Cycles are repeated every 21 days provided there is no delay, and will be administered on day 6 of each cycle.
Period Title: Overall Study
STARTED	12
COMPLETED	12
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Paclitaxel and CBT-1 to Treat Solid Tumors
Arm/Group Description	Patients will be treated with oral CBT-1 at a dose of 500 mg/m^2 daily for 7 days in divided doses and repeated every 21 days for 7 days beginning with cycle 1 of each cycle provided cycles are not delayed. Paclitaxel will be 135 mg/m^2 intravenously on day 6 over 180 minutes. Cycles are repeated every 21 days provided there is no delay, and will be administered on day 6 of each cycle.
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	9 75%
>=65 years	3 25%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.79 (9.50)
Sex: Female, Male (Count of Participants)
Female	4 33.3%
Male	8 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	12 100%
Unknown or Not Reported	0 0%
Race/Ethnicity, Customized (Number) [Number]
White	11 91.7%
Asian	1 8.3%
Region of Enrollment (participants) [Number]
United States	12 100%

Outcome Measures

1. Primary Outcome

Title	Percent Increase in Sestamibi Retention in the Liver as a Measure of P-glycoprotein Inhibition
Description	An area under the concentration curve (AUC) was calculated for 99mTc counts over the liver, lungs, and heart. An equation was applied to determine the increase in sestamibi in the liver: [(AUCpost - AUC baseline)/(AUC baseline)] x 100.
Time Frame	sestamibi scanning was performed on day 0 and day 6, allowing scans to be performed pre and post CBT-1 administration

Outcome Measure Data

Analysis Population Description

As planned imaging data from 10 pts were analyzed.

Arm/Group Title	Paclitaxel and CBT-1 to Treat Solid Tumors
Arm/Group Description	Patients will be treated with oral CBT-1 at a dose of 500 mg/m^2 daily for 7 days in divided doses and repeated every 21 days for 7 days beginning with cycle 1 of each cycle provided cycles are not delayed. Paclitaxel will be 135 mg/m^2 intravenously on day 6 over 180 minutes. Cycles are repeated every 21 days provided there is no delay, and will be administered on day 6 of each cycle.
Measure Participants	10
Median (Full Range) [percent increase sestamibi retention]	71.9

2. Primary Outcome

Title	Number of Participants With Adverse Events
Description	Here are the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paclitaxel and CBT-1 to Treat Solid Tumors
Arm/Group Description	Patients will be treated with oral CBT-1 at a dose of 500 mg/m^2 daily for 7 days in divided doses and repeated every 21 days for 7 days beginning with cycle 1 of each cycle provided cycles are not delayed. Paclitaxel will be 135 mg/m^2 intravenously on day 6 over 180 minutes. Cycles are repeated every 21 days provided there is no delay, and will be administered on day 6 of each cycle.
Measure Participants	12
Number [Participants]	12 100%

3. Secondary Outcome

Title	Percent Inhibition of Rhodamine Efflux From CD56+Cells Post Treatment
Description	Rhodamine 123 was added to whole blood obtained before and after CBT-1. The blood was incubated, layered on lymphocyte separation medium and centrifuged. Peripheral blood mononuclear cells(PBMCs)were isolated, washed and incubated in rhodamine-free medium with or without valspodar. Cells were washed and incubated in phycoerythrin-labeled anti-CD56 antibody or negative control antibody. Rhodamine 123 fluorescence was assessed in CD56+cells with or without valspodar and a 60 min efflux period,continuing the cells without or with valspodar to generate Efflux and PSC/Efflux histograms.
Time Frame	Rhodamine efflux was performed on blood drawn prior to CBT-1 ingestion and after 6 days of dosing.

Outcome Measure Data

Analysis Population Description

Rhodamine 123 fluorescence was assessed in CD56+cells after a 30 min loading period with or without exogenously added valspodar and a 60 min efflux period followed, continuing the cells with or without exogenous valspodar to generate Efflux and PSC/Efflux histograms. Percent decrease in difference between these histograms is reported.

Arm/Group Title	Paclitaxel and CBT-1 to Treat Solid Tumors
Arm/Group Description	Patients will be treated with oral CBT-1 at a dose of 500 mg/m^2 daily for 7 days in divided doses and repeated every 21 days for 7 days beginning with cycle 1 of each cycle provided cycles are not delayed. Paclitaxel will be 135 mg/m^2 intravenously on day 6 over 180 minutes. Cycles are repeated every 21 days provided there is no delay, and will be administered on day 6 of each cycle.
Measure Participants	12
Mean (Full Range) [Percent inhibition of rhodamine efflux]	78

4. Secondary Outcome

Title	Number of Participants Who Had an Overall Response
Description	Response is determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Complete response (CR)-disappearance of all target lesions, Partial response (PR)-at least a 30% decrease in the sum of the longest diameter(LD)of target lesions, stable disease (SD) - neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. See the Protocol Link module for further details about the RECIST Criteria.
Time Frame	Baseline to progression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paclitaxel and CBT-1 to Treat Solid Tumors
Arm/Group Description	Patients will be treated with oral CBT-1 at a dose of 500 mg/m^2 daily for 7 days in divided doses and repeated every 21 days for 7 days beginning with cycle 1 of each cycle provided cycles are not delayed. Paclitaxel will be 135 mg/m^2 intravenously on day 6 over 180 minutes. Cycles are repeated every 21 days provided there is no delay, and will be administered on day 6 of each cycle.
Measure Participants	12
Number [participants with response]	2 16.7%

Adverse Events

Time Frame	18 months
Arm/Group Title	Paclitaxel and CBT-1 to Treat Solid Tumors
Arm/Group Description	Patients will be treated with oral CBT-1 at a dose of 500 mg/m^2 daily for 7 days in divided doses and repeated every 21 days for 7 days beginning with cycle 1 of each cycle provided cycles are not delayed. Paclitaxel will be 135 mg/m^2 intravenously on day 6 over 180 minutes. Cycles are repeated every 21 days provided there is no delay, and will be administered on day 6 of each cycle.
All Cause Mortality
	Paclitaxel and CBT-1 to Treat Solid Tumors
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Paclitaxel and CBT-1 to Treat Solid Tumors
	Affected / at Risk (%)	# Events
Total	3/12 (25%)
Cardiac disorders
Pericardial Effusion	1/12 (8.3%)	1
Infections and infestations
Infection (pneumonia)with normal absolute neutrophil count (ANC)	1/12 (8.3%)	1
Vascular disorders
Other: SVC (Superior vena cava) Syndrome	1/12 (8.3%)	1
Other (Not Including Serious) Adverse Events
	Paclitaxel and CBT-1 to Treat Solid Tumors
	Affected / at Risk (%)	# Events
Total	12/12 (100%)
Cardiac disorders
OTHER: PULMONARY STENOSIS NOS	2/12 (16.7%)	2
PAIN, CHEST/THORAX NOS	4/12 (33.3%)	4
PLEURAL EFFUSION	1/12 (8.3%)	1
Endocrine disorders
HYPOTHYROIDISM	1/12 (8.3%)	1
Eye disorders
BLURRED VISION	1/12 (8.3%)	1
Gastrointestinal disorders
CONSTIPATION	4/12 (33.3%)	5
DIARRHEA	9/12 (75%)	16
DISTENTION	1/12 (8.3%)	1
DRY MOUTH	1/12 (8.3%)	1
HEARTBURN	3/12 (25%)	5
HEMORRHAGE-GI, UPPER GI NOS	1/12 (8.3%)	1
MUCOSITIS (CLINICAL EXAM), ORAL CAVITY	2/12 (16.7%)	2
NAUSEA	10/12 (83.3%)	14
PAIN, THROAT/PHARYNX/LARYNX	1/12 (8.3%)	1
PAIN, ABD NOS	6/12 (50%)	8
PAIN, RECTUM	1/12 (8.3%)	1
TASTE ALTERATION	2/12 (16.7%)	2
VOMITING	9/12 (75%)	12
General disorders
EDEMA, H&N	2/12 (16.7%)	2
EDEMA, LIMB	3/12 (25%)	3
FATIGUE	10/12 (83.3%)	17
FEVER	3/12 (25%)	3
PAIN NOS	2/12 (16.7%)	2
RIGORS/CHILLS	2/12 (16.7%)	2
Immune system disorders
ALLERGIC REACTION	1/12 (8.3%)	1
Infections and infestations
HEMOGLOBIN	12/12 (100%)	25
INFECTION, URINARY TRACT NOS	1/12 (8.3%)	1
OTHER: INFECTION NOS	2/12 (16.7%)	2
Injury, poisoning and procedural complications
OTHER: PERFORATION NOS	1/12 (8.3%)	1
Investigations
ALKALINE PHOSPHATASE	6/12 (50%)	8
ALT/SGPT	5/12 (41.7%)	10
AST/SGOT	8/12 (66.7%)	12
BICARBONATE, SERUM LOW	2/12 (16.7%)	3
BILIRUBIN	4/12 (33.3%)	5
CREATININE	1/12 (8.3%)	3
INR	1/12 (8.3%)	1
LEUKOCYTES	9/12 (75%)	14
LYMPHOPENIA	2/12 (16.7%)	2
NEUTROPHILS	8/12 (66.7%)	12
OTHER: LDH	4/12 (33.3%)	4
PLATELETS	5/12 (41.7%)	9
PTT	1/12 (8.3%)	1
Metabolism and nutrition disorders
ANOREXIA	6/12 (50%)	9
HYPERCALCEMIA	1/12 (8.3%)	1
HYPERGLYCEMIA	12/12 (100%)	28
HYPERKALEMIA	1/12 (8.3%)	1
HYPERURICEMIA	3/12 (25%)	4
HYPOALBUMINEMIA	12/12 (100%)	17
HYPOCALCEMIA	3/12 (25%)	5
HYPOGLYCEMIA	1/12 (8.3%)	1
HYPOKALEMIA	3/12 (25%)	4
HYPOMAGNESEMIA	7/12 (58.3%)	8
HYPONATREMIA	8/12 (66.7%)	11
HYPOPHOSPHATEMIA	6/12 (50%)	10
HYPERMAGNESEMIA	1/12 (8.3%)	1
Musculoskeletal and connective tissue disorders
OTHER: RUQ PAIN	1/12 (8.3%)	1
PAIN, BACK	3/12 (25%)	3
PAIN, JOINT	6/12 (50%)	10
PAIN, MUSCLE	3/12 (25%)	4
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PAIN, TUMOR	1/12 (8.3%)	1
Nervous system disorders
ATAXIA	3/12 (25%)	4
DIZZINESS	2/12 (16.7%)	3
NEUROPATHY-CRANIAL: CN-V MOTOR-JAW MUSCLES; SENSORY-FACIAL	1/12 (8.3%)	1
NEUROPATHY-SENSORY	5/12 (41.7%)	5
PAIN, HEAD/HEADACHE	1/12 (8.3%)	1
Psychiatric disorders
CONFUSION	1/12 (8.3%)	1
MOOD ALTERATION-ANXIETY	2/12 (16.7%)	2
MOOD ALTERATION, DEPRESSION	1/12 (8.3%)	1
Renal and urinary disorders
HEMOGLOBINURIA	1/12 (8.3%)	1
OTHER: DYSURIA	1/12 (8.3%)	1
PROTEINURIA	6/12 (50%)	7
URINARY RETENTION	2/12 (16.7%)	2
Respiratory, thoracic and mediastinal disorders
ALLERGIC RHINITIS	2/12 (16.7%)	3
COUGH	4/12 (33.3%)	5
DYSPNEA	8/12 (66.7%)	9
VOICE CHANGES	1/12 (8.3%)	1
Skin and subcutaneous tissue disorders
ALOPECIA	3/12 (25%)	3
HYPERPIGMENTATION	1/12 (8.3%)	1
NAIL CHANGES	1/12 (8.3%)	1
PRURITIS	1/12 (8.3%)	1
DRY SKIN	1/12 (8.3%)	1
Vascular disorders
FLUSHING	1/12 (8.3%)	1
HYPERTENSION	3/12 (25%)	3
HYPOTENSION	3/12 (25%)	3
OTHER: LYMPHEDEMA	1/12 (8.3%)	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.