Tariquidar and Docetaxel to Treat Patients With Lung, Ovarian, Renal and Cervical Cancer
Study Details
Study Description
Brief Summary
The purpose of this study is three-fold: 1) to examine the ability of the experimental drug tariquidar to improve chemotherapy results by blocking a protein (P-glycoprotein) on some cancer cells that acts to pump out cancer drugs; 2) examine how tariquidar interacts with the cancer drug docetaxel; and 3) evaluate the effectiveness of combination treatment with tariquidar and docetaxel in treating patients with lung, ovarian, or cervical cancer.
Patients 18 years of age and older with recurrent or metastatic (spreading) lung, cervical, or ovarian cancer who cannot benefit from any standard treatment may be eligible for this study. Candidates will be screened with a medical history and physical examination; review of pathology slides; blood and urine tests; imaging tests, including computed tomography (CT) or magnetic resonance imaging (MRI) scans; chest x-ray, electrocardiogram (EKG); and possibly echocardiogram.
Participants will undergo the following tests and procedures:
Blood draw. Blood is drawn before treatment begins to establish baseline levels for future blood tests. Blood counts are done twice weekly after chemotherapy begins.
Central venous catheter placement. A plastic tube is put into a major vein in the chest. It is used to give the study drugs or other medications, including antibiotics and blood transfusions, if needed, and to withdraw blood samples. The line is usually placed under local anesthesia in the radiology department or the operating room. It can stay in the body for months or be removed after each treatment is completed.
Chemotherapy. Treatment cycles are 21 days. Both drugs are given on day 1 of each cycle. First, tariquidar is given as a 30-minute infusion. One hour after the tariquidar infusion, docetaxel is infused over 1 hour. (For the first cycle only, docetaxel is given in divided doses one week apart and tariquidar is administered on either day 1 or day 8. The order of tariquidar administration is randomized to generate optimal pharmacokinetic data. Patients will be hospitalized for several days during this cycle to gather research data). The tariquidar dose remains the same throughout the study. Docetaxel may be increased or decreased from cycle to cycle, based on side effects.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
Intrinsic and acquired drug resistance remain major obstacles in the treatment of cancer. Accumulating evidence indicates that in some malignancies P-glycoprotein (Pgp) can confer resistance, and that its reversal can improve therapeutic outcome. Clinical trials investigating Pgp antagonists have been hampered by the occurrence of unpredictable pharmacokinetic interactions, which have required dose reductions of the chemotherapeutic agents to avert excessive toxicity. Tariquidar (XR9576) is a new Pgp antagonist that is more potent and has prolonged activity. Phase I trials with paclitaxel, vinorelbine, and docetaxel have demonstrated that tariquidar (XR9576) has minimal pharmacokinetic interactions while surrogate studies have confirmed in vivo inhibition of Pgp-mediated drug transport.This study seeks to determine the pharmacokinetic interaction, if any between docetaxel and tariquidar and to evaluate the potential for activity in lung, ovarian, primary peritoneal, fallopian tube and cervical cancers. Renal cell cancer has been added in a 3/1/06 amendment. The secondary goal is to evaluate the impact of tariquidar on uptake of (99m)Tc-sestamibi in recurrent or metastatic tumors of patients with lung, ovarian, renal or cervical cancer.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Pts who received docetaxel on day 1, 8, & tariquidar day 8,22 Patients receive 40 mg/m^2 docetaxel intravenous (IV) over 1 hour on days 1 and 8 and 150 mg tariquidar intravenous (IV) over 30 minutes on days 8 and 22. From cycle 2 and onward 75 mg/m^2 docetaxel was administered every 21 days in combination with a single 150 mg dose. |
Drug: docetaxel
Patients receive docetaxel intravenous (IV) over 1 hour on days 1 and 8.
Other Names:
Drug: tariquidar
Patients receive tariquidar intravenous (IV) over 30 minutes on days 8 and 22.
Other Names:
Other: 99mTc-sestamibi imaging
Bolus injection of 29 mCi of 99mTc-sestamibi intravenously for each imaging study.
Other Names:
|
Experimental: Pts who received docetaxel on days 1, 8, & tariquidar day 1,22 Patients receive docetaxel intravenous (IV) over 1 hour on days 1 and 8 and tariquidar intravenous (IV) over 30 minutes on days 1 and 22. |
Drug: docetaxel
Patients receive docetaxel intravenous (IV) over 1 hour on days 1 and 8.
Other Names:
Drug: tariquidar
Patients receive tariquidar intravenous (IV) over 30 minutes on days 8 and 22.
Other Names:
Other: 99mTc-sestamibi imaging
Bolus injection of 29 mCi of 99mTc-sestamibi intravenously for each imaging study.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Geometric Mean of Maximum Concentration of the Drug (Cmax) [24 hours]
In the first cycle patients were to receive docetaxel on days 1 and 8 and to be randomized to receive tariquidar on either day 1 or 8. Thus pharmacokinetic data with and without tariquidar can be compared.
- The Number of Participants With Adverse Events. [4 yrs 8-11 months]
Here are the total number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
- Geometric Mean of Area Under Curve (AUC0)-24 [24 hours]
- Clinical Response Rate [4 years, 8-11 months]
Response is determined by RECIST criteria defined as changes in only the largest diameter (unidimensional measurement) of the tumor lesion. Lesions are either measurable or non-measurable. Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as >/- 20 mm with conventional techniques (CT, MRI, xray) or as >/- 10 mm with a spiral CT scan. Non-measurable lesions are defined as all other lesions (or sites of disease) including small lesions (longest diameter <20 mm with conventional techniques or <10 mm using spiral CT.
Secondary Outcome Measures
- Percent Increase in Sestamibi Area Under Curve (AUC) in Liver After Tariquidar [3 - 24 hours]
A significant change in the area under the curve(AUC) in liver tissue (normal tissue as a surrogate) is defined as P<0.001. A secondary objective of this study was to establish whether tariquidar (150 mg) modulates Pgp in liver. Sestamibi is a Pgp substrate that may be a surrogate for measuring drug efflux from tumors. A baseline Tc-sestamibi scan was obtained before the administration of tariquidar. A minimum of 48 hours later, on or about day 22 a single dose of tariquidar was administered, followed by a second Tc-sestamibi scan.
- Percent Increase in Sestamibi Area Under Curve (AUC) in Tumor Tissue [3-24 hours]
99mTc-sestamibi is a radionuclide imaging agent used to study cardiac function that has also been shown to be a substrate for P-glycoprotein- mediated drug efflux. Because of the high expression of Pgp in liver tissue, sestamibi uptake in liver tissue is often monitored as a marker of Pgp inhibition. A significant change in the area under the curve(AUC) in liver tissue (normal tissue as a surrogate) is defined as P<0.001.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients must fulfill all of the following criteria to be eligible for study admission:
-
Age greater than or equal to 18 years.
-
Histologic or cytologic confirmation of lung, cervical, or ovarian cancer, following at least one standard treatment regimen, and for which there is no known standard therapy capable of extending life expectancy. Female patients with primary papillary carcinoma of the peritoneum and fallopian tube cancers will be included in the latter group, as the disease entities are closely associated with epithelial ovarian carcinoma, can be difficult to distinguish, have a similar epithelial origin, and are treated in an identical manner.
-
Histologic or cytologic confirmation of renal cell carcinoma (clear cell, type 1 and type II papillary chromophobe, collecting duct and medullary). Patients should have received either sunitinib or sorafenib, unless deemed ineligible for treatment with either agent. In addition,patient should either: (a) have received IL-2; (b) have been evaluated for therapy with Interleukin-2 (IL- 2) and deemed to be ineligible; or (c) have been evaluated for therapy with IL2 and refused treatment.
-
Performance status: Eastern Cooperative Oncology Group (ECOG) 0-2
-
Life expectancy of 3 months or greater.
-
Suitable candidate for receiving planned therapy as evidenced by screening laboratory assessments hematologic, renal hepatic, and metabolic functions, platelet count greater than or equal to 90,000/mL, absolute granulocyte count(AGC) greater than or equal to 1,500/mL, serum creatinine greater than or equal to 1,500/mL, serum creatine less than or equal to 1.5 mg/dl )or if greater than 1.5 a measured 24 hour creatinine clearance greater than or equal to 50 mL/min) and serum glutamic oxaloacetic transaminase (SGOT) less than or equal to 2.5 x normal limit (NL) and bilirubin less than or equal to 1.5 x NL (in patients with clinical evidence of Gilbert's disease,less than or equal to 3 x NL).
-
Patients must be greater than or equal to 4 weeks prior radiation or chemotherapy, greater than 2 weeks from hormonal therapy; greater than 4 weeks from prior experimental therapy; greater than 6 weeks from mitomycin C; and greater than 8 weeks from prior UCN01 treatment.
-
No serious intercurrent medical illness.
-
Measurable disease by radiographic means or physical examination. For ovarian cancer, assessable disease by cancer antigen 125 (CA125) measurement is allowed.
-
Willingness to sign a written consent form, and to comply with the protocol.
Exclusion Criteria:
-
The following patient populations are not eligible for this study.
-
Pregnant or nursing women are not eligible; women of childbearing age must agree to use an effective method of contraception. Pregnant women are not eligible because of teratogenic effects of chemotherapy.
-
The presence of a second malignancy that has not received primary treatment or would complicate the primary objective of this study.
-
Patients who are poor medical risk because of active, uncontrolled infection or other nonmalignant systemic disease.
-
Human immunodeficiency virus (HIV) seropositive patients. Patients infected with the HIV virus will be excluded from this trial because the effect of the combination of tariquidar and docetaxel on HIV replication and/or the immune system is unknown and potentially harmful.
-
Patients receiving agents which have major interactions with the cytochrome P450 3A4 (CYP3A4)drug metabolizing system and which cannot be discontinued may not be included in the trial.
-
Untreated brain metastases (or local treatment of brain metastases within the last 6 months) due to the poor prognosis of these patients and difficulty ascertaining the cause of neurologic toxicities.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | National Institutes of Health | Bethesda | Maryland | United States | 20892 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Susan E Bates, M.D., NCI, NIH
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Akiyama S, Fojo A, Hanover JA, Pastan I, Gottesman MM. Isolation and genetic characterization of human KB cell lines resistant to multiple drugs. Somat Cell Mol Genet. 1985 Mar;11(2):117-26.
- Beck WT, Cirtain MC, Lefko JL. Energy-dependent reduced drug binding as a mechanism of Vinca alkaloid resistance in human leukemic lymphoblasts. Mol Pharmacol. 1983 Nov;24(3):485-92.
- Ling V, Thompson LH. Reduced permeability in CHO cells as a mechanism of resistance to colchicine. J Cell Physiol. 1974 Feb;83(1):103-16.
- 030284
- 03-C-0284
- 030284
- NCT00072202
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Pts Who Received Docetaxel on Day 1, 8, & Tariquidar Day 8,22 | Pts Who Received Docetaxel on Days 1, 8, & Tariquidar Day 1,22 |
---|---|---|
Arm/Group Description | Patients receive 40 mg/m^2 docetaxel intravenous (IV) over 1 hour on days 1 and 8 and 150 mg tariquidar intravenous (IV) over 30 minutes on days 8 and 22. From cycle 2 and onward 75 mg/m^2 docetaxel was administered every 21 days in combination with a single 150 mg tariquidar dose. | Patients receive docetaxel intravenous (IV) over 1 hour on days 1 and 8 and tariquidar intravenous (IV) over 30 minutes on days 1 and 22.From cycle 2 and onward 75 mg/m^2 docetaxel was administered every 21 days in combination with a single 150 mg tariquidar dose. |
Period Title: Overall Study | ||
STARTED | 23 | 25 |
COMPLETED | 23 | 25 |
NOT COMPLETED | 0 | 0 |
Baseline Characteristics
Arm/Group Title | Pts Who Received Docetaxel on Day 1, 8, & Tariquidar Day 8,22 | Pts Who Received Docetaxel on Days 1, 8, & Tariquidar Day 1,22 | Total |
---|---|---|---|
Arm/Group Description | Patients receive 40 mg/m^2 docetaxel intravenous (IV) over 1 hour on days 1 and 8 and 150 mg tariquidar intravenous (IV) over 30 minutes on days 8 and 22. From cycle 2 and onward 75 mg/m^2 docetaxel was administered every 21 days in combination with a single 150 mg tariquidar dose. | Patients receive docetaxel intravenous (IV) over 1 hour on days 1 and 8 and tariquidar intravenous (IV) over 30 minutes on days 1 and 22.From cycle 2 and onward 75 mg/m^2 docetaxel was administered every 21 days in combination with a single 150 mg tariquidar dose. | Total of all reporting groups |
Overall Participants | 23 | 25 | 48 |
Age (Count of Participants) | |||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
19
82.6%
|
20
80%
|
39
81.3%
|
>=65 years |
4
17.4%
|
5
20%
|
9
18.8%
|
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
50.76
(9.54)
|
55.77
(9.57)
|
53.37
(9.79)
|
Sex: Female, Male (Count of Participants) | |||
Female |
18
78.3%
|
20
80%
|
38
79.2%
|
Male |
5
21.7%
|
5
20%
|
10
20.8%
|
Region of Enrollment (participants) [Number] | |||
United States |
23
100%
|
25
100%
|
48
100%
|
Outcome Measures
Title | Geometric Mean of Maximum Concentration of the Drug (Cmax) |
---|---|
Description | In the first cycle patients were to receive docetaxel on days 1 and 8 and to be randomized to receive tariquidar on either day 1 or 8. Thus pharmacokinetic data with and without tariquidar can be compared. |
Time Frame | 24 hours |
Outcome Measure Data
Analysis Population Description |
---|
Docetaxel alone (C1D1 = 21 patients; C1D8 = 18 patients) Docetaxel with Tariquidar (C1D1 = 21 patients; C1D8 = 16 patients) Data were evaluable in 39 patients. Paired data from 31 participants were evaluable. |
Arm/Group Title | Docetaxel Alone | With Tariquidar |
---|---|---|
Arm/Group Description | 40 mg/m^2 docetaxel over 1 hour on days 1 and 8. | 40 mg/m^2 docetaxel intravenous (IV) over 1 hour on days 1 and 8 and 150 mg tariquidar intravenous (IV) over 30 minutes on either day 1 or 8 and then again on day 22. From cycle 2 and onward 75 mg/m^2 docetaxel was administered every 21 days in combination with a single 150 mg dose of tariquidar. |
Measure Participants | 39 | 37 |
C1D1 |
1315
|
1093
|
C1D8 |
1060
|
1026
|
Both Groups (C1D1 + C1D8) |
1190
|
1063
|
Title | The Number of Participants With Adverse Events. |
---|---|
Description | Here are the total number of participants with adverse events. For the detailed list of adverse events see the adverse event module. |
Time Frame | 4 yrs 8-11 months |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Patients on Docetaxel on Days 1, 8 & Tariquidar on Day 8, 22 | Patients on Docetaxel on Days 1, 8 & Tariquidar on Days 1, 22 |
---|---|---|
Arm/Group Description | Patients receive 40 mg/m^2 docetaxel intravenous (IV) over 1 hour on days 1 and 8 and 150 mg tariquidar intravenous (IV) over 30 minutes on days 8 and 22. From cycle 2 and onward 75 mg/m^2 docetaxel was administered every 21 days in combination with a single 150 mg dose. | Patients receive 40 mg/m^2 docetaxel intravenous (IV) over 1 hour on days 1 and 8 and 150 mg tariquidar intravenous (IV) over 30 minutes on days 8 and 22. From cycle 2 and onward 75 mg/m^2 docetaxel was administered every 21 days in combination with a single 150 mg dose. |
Measure Participants | 23 | 25 |
Number [participants] |
23
100%
|
25
100%
|
Title | Geometric Mean of Area Under Curve (AUC0)-24 |
---|---|
Description | |
Time Frame | 24 hours |
Outcome Measure Data
Analysis Population Description |
---|
Docetaxel alone (C1D1 = 21 patients; C1D8 = 18 patients) Docetaxel with Tariquidar (C1D1 = 21 patients; C1D8 = 16 patients) Pharmacokinetic data were evaluable in 39 patients. Paired data from 31 participants were evaluable. |
Arm/Group Title | Docetaxel Alone | With Tariquidar |
---|---|---|
Arm/Group Description | 40 mg/m^2 docetaxel over 1 hour on days 1 and 8. | 40 mg/m^2 docetaxel intravenous (IV) over 1 hour on days 1 and 8 and 150 mg tariquidar intravenous (IV) over 30 minutes on either day 1 or 8 and then again on day 22. From cycle 2 and onward 75 mg/m^2 docetaxel was administered every 21 days in combination with a single 150 mg dose of tariquidar. |
Measure Participants | 39 | 37 |
C1D1 |
1367
|
1409
|
C1D8 |
1308
|
1327
|
Both Groups (C1D1 + C1D8) |
1339
|
1373
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Docetaxel Alone, With Tariquidar |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | >.05 |
Comments | ||
Method | t-test, 2 sided | |
Comments |
Title | Clinical Response Rate |
---|---|
Description | Response is determined by RECIST criteria defined as changes in only the largest diameter (unidimensional measurement) of the tumor lesion. Lesions are either measurable or non-measurable. Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as >/- 20 mm with conventional techniques (CT, MRI, xray) or as >/- 10 mm with a spiral CT scan. Non-measurable lesions are defined as all other lesions (or sites of disease) including small lesions (longest diameter <20 mm with conventional techniques or <10 mm using spiral CT. |
Time Frame | 4 years, 8-11 months |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | All Patients Who Received Docetaxel and Tariquidar |
---|---|
Arm/Group Description | Patients receive 40 mg/m^2 docetaxel intravenous (IV) over 1 hour on days 1 and 8 and 150 mg tariquidar intravenous (IV) over 30 minutes on days 8 and 22. From cycle 2 and onward 75 mg/m^2 docetaxel was administered every 21 days in combination with a single 150 mg dose. |
Measure Participants | 48 |
Number [Percentage of participants] |
8
34.8%
|
Title | Percent Increase in Sestamibi Area Under Curve (AUC) in Liver After Tariquidar |
---|---|
Description | A significant change in the area under the curve(AUC) in liver tissue (normal tissue as a surrogate) is defined as P<0.001. A secondary objective of this study was to establish whether tariquidar (150 mg) modulates Pgp in liver. Sestamibi is a Pgp substrate that may be a surrogate for measuring drug efflux from tumors. A baseline Tc-sestamibi scan was obtained before the administration of tariquidar. A minimum of 48 hours later, on or about day 22 a single dose of tariquidar was administered, followed by a second Tc-sestamibi scan. |
Time Frame | 3 - 24 hours |
Outcome Measure Data
Analysis Population Description |
---|
Percent increase in sestamibi AUC in liver after tariquidar. |
Arm/Group Title | All Patients Who Received Docetaxel and Tariquidar |
---|---|
Arm/Group Description | Patients receive 40 mg/m^2 docetaxel intravenous (IV) over 1 hour on days 1 and 8 and 150 mg tariquidar intravenous (IV) over 30 minutes on days 8 and 22. From cycle 2 and onward 75 mg/m^2 docetaxel was administered every 21 days in combination with a single 150 mg dose. |
Measure Participants | 35 |
Median (Full Range) [percent increase in sestamibi AUC] |
82.2
|
Title | Percent Increase in Sestamibi Area Under Curve (AUC) in Tumor Tissue |
---|---|
Description | 99mTc-sestamibi is a radionuclide imaging agent used to study cardiac function that has also been shown to be a substrate for P-glycoprotein- mediated drug efflux. Because of the high expression of Pgp in liver tissue, sestamibi uptake in liver tissue is often monitored as a marker of Pgp inhibition. A significant change in the area under the curve(AUC) in liver tissue (normal tissue as a surrogate) is defined as P<0.001. |
Time Frame | 3-24 hours |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | All Patients Who Received Docetaxel and Tariquidar |
---|---|
Arm/Group Description | Patients receive 40 mg/m^2 docetaxel intravenous (IV) over 1 hour on days 1 and 8 and 150 mg tariquidar intravenous (IV) over 30 minutes on days 8 and 22. From cycle 2 and onward 75 mg/m^2 docetaxel was administered every 21 days in combination with a single 150 mg dose. |
Measure Participants | 31 |
Median (Full Range) [Percent] |
12.4
|
Adverse Events
Time Frame | 4 years and 11 months | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | Patients on Docetaxel on Days 1, 8 & Tariquidar on Day 8, 22 | Patients on Docetaxel on Days 1, 8 & Tariquidar on Days 1, 22 | ||
Arm/Group Description | Patients receive 40 mg/m^2 docetaxel intravenous (IV) over 1 hour on days 1 and 8 and 150 mg tariquidar intravenous (IV) over 30 minutes on days 8 and 22. From cycle 2 and onward 75 mg/m^2 docetaxel was administered every 21 days in combination with a single 150 mg dose. | Patients receive 40 mg/m^2 docetaxel intravenous (IV) over 1 hour on days 1 and 8 and 150 mg tariquidar intravenous (IV) over 30 minutes on days 8 and 22. From cycle 2 and onward 75 mg/m^2 docetaxel was administered every 21 days in combination with a single 150 mg dose. | ||
All Cause Mortality |
||||
Patients on Docetaxel on Days 1, 8 & Tariquidar on Day 8, 22 | Patients on Docetaxel on Days 1, 8 & Tariquidar on Days 1, 22 | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
Patients on Docetaxel on Days 1, 8 & Tariquidar on Day 8, 22 | Patients on Docetaxel on Days 1, 8 & Tariquidar on Days 1, 22 | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 6/23 (26.1%) | 8/25 (32%) | ||
Cardiac disorders | ||||
CARDIOVASCULAR (GENERAL):: Hypotension | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
CARDIOVASCULAR (GENERAL):: Thrombosis/embolism | 0/23 (0%) | 0 | 2/25 (8%) | 2 |
Gastrointestinal disorders | ||||
GASTROINTESTINAL:: Anorexia | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
HEMORRHAGE:: Rectal bleeding/hematochezia | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
General disorders | ||||
CONSTITUTIONAL SYMPTOMS:: Fatigue (lethargy, malaise, asthenia) | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
CONSTITUTIONAL SYMPTOMS:: | 1/23 (4.3%) | 1 | 2/25 (8%) | 2 |
CONSTITUTIONAL SYMPTOMS:: Rigors, chills | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
Infections and infestations | ||||
INFECTION/FEBRILE NEUTROPENIA:: Febrile neutropenia (fever of unknown origin without clinically or m | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
Investigations | ||||
BLOOD/BONE MARROW:: Leukocytes (total WBC) | 1/23 (4.3%) | 1 | 1/25 (4%) | 1 |
BLOOD/BONE MARROW:: Neutrophils/granulocytes (ANC/AGC) | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
HEPATIC:: Alkaline phosphatase | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
HEPATIC:: SGOT (AST) (serum glutamic oxaloacetic transaminase) | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
HEPATIC:: SGPT (ALT) (serum glutamic pyruvic transaminase) | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
Metabolism and nutrition disorders | ||||
METABOLIC/LABORATORY:: Hyponatremia | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
Musculoskeletal and connective tissue disorders | ||||
MUSCULOSKELETAL:: Musculoskeletal-Other (Specify,musculoskeletal-lethargic) | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
MUSCULOSKELETAL:: Muscle weakness (not due to neuropathy) | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
Nervous system disorders | ||||
NEUROLOGY:: Dizziness/lightheadedness | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
NEUROLOGY:: Depressed level of consciousness | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
NEUROLOGY:: Mood alteration-anxiety, agitation | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
Renal and urinary disorders | ||||
Urinary frequency/urgency | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||||
PULMONARY:: Dyspnea (shortness of breath) | 2/23 (8.7%) | 2 | 3/25 (12%) | 3 |
PULMONARY:: Pulmonary-Other (Specify,clinical deterioration) | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
PULMONARY:: Cough | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
Hypoxia | 1/23 (4.3%) | 1 | 1/25 (4%) | 1 |
Pneumothorax | 1/23 (4.3%) | 1 | 1/25 (4%) | 1 |
Skin and subcutaneous tissue disorders | ||||
DERMATOLOGY/SKIN:: Alopecia | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
Patients on Docetaxel on Days 1, 8 & Tariquidar on Day 8, 22 | Patients on Docetaxel on Days 1, 8 & Tariquidar on Days 1, 22 | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 23/23 (100%) | 25/25 (100%) | ||
Blood and lymphatic system disorders | ||||
BLOOD/BONE MARROW:: Hemoglobin | 18/23 (78.3%) | 130 | 21/25 (84%) | 72 |
BLOOD/BONE MARROW:: Leukocytes (total WBC) | 18/23 (78.3%) | 86 | 21/25 (84%) | 77 |
BLOOD/BONE MARROW:: Lymphopenia | 2/23 (8.7%) | 9 | 4/25 (16%) | 21 |
BLOOD/BONE MARROW:: Neutrophils/granulocytes (ANC/AGC) | 19/23 (82.6%) | 62 | 16/25 (64%) | 41 |
BLOOD/BONE MARROW:: Platelets | 7/23 (30.4%) | 22 | 6/25 (24%) | 31 |
BLOOD/BONE MARROW:: Transfusion: pRBCs | 3/23 (13%) | 5 | 9/25 (36%) | 11 |
COAGULATION:: Partial thromboplastin time (PTT) | 9/23 (39.1%) | 17 | 6/25 (24%) | 10 |
COAGULATION:: Prothrombin time (PT) | 3/23 (13%) | 6 | 4/25 (16%) | 13 |
HEMORRHAGE:: CNS hemorrhage/bleeding | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
Cardiac disorders | ||||
CARDIOVASCULAR (ARRHYTHMIA):: Sinus tachycardia | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
CARDIOVASCULAR (GENERAL):: Edema | 7/23 (30.4%) | 18 | 8/25 (32%) | 8 |
CARDIOVASCULAR (GENERAL):: Hypertension | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
CARDIOVASCULAR (GENERAL):: Hypotension | 2/23 (8.7%) | 2 | 1/25 (4%) | 1 |
CARDIOVASCULAR (GENERAL):: Phlebitis (superficial) | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
CARDIOVASCULAR (GENERAL):: Thrombosis/embolism | 2/23 (8.7%) | 3 | 1/25 (4%) | 1 |
CARDIOVASCULAR (ARRHYTHMIA):: Palpitations | 0/23 (0%) | 0 | 1/25 (4%) | 2 |
Ear and labyrinth disorders | ||||
AUDITORY/HEARING:: Middle ear/hearing | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
PAIN:: Earache (otalgia) | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
Eye disorders | ||||
OCULAR/VISUAL:: Conjunctivitis | 2/23 (8.7%) | 2 | 0/25 (0%) | 0 |
OCULAR/VISUAL:: Dry eye | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
OCULAR/VISUAL:: Tearing (watery eyes) | 9/23 (39.1%) | 11 | 6/25 (24%) | 10 |
OCULAR/VISUAL:: Ocular/Visual-Other (Specify,___) | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
OCULAR/VISUAL:: Vision-blurred vision | 0/23 (0%) | 0 | 2/25 (8%) | 2 |
Gastrointestinal disorders | ||||
GASTROINTESTINAL:: Anorexia | 12/23 (52.2%) | 21 | 13/25 (52%) | 21 |
GASTROINTESTINAL:: Constipation | 10/23 (43.5%) | 13 | 4/25 (16%) | 5 |
GASTROINTESTINAL:: Dehydration | 1/23 (4.3%) | 1 | 1/25 (4%) | 1 |
GASTROINTESTINAL:: Diarrhea patients without colostomy | 17/23 (73.9%) | 33 | 17/25 (68%) | 37 |
GASTROINTESTINAL:: Dyspepsia/heartburn | 3/23 (13%) | 5 | 2/25 (8%) | 2 |
GASTROINTESTINAL:: Dysphagia, esophagitis, odynophagia (painful swallowing) | 1/23 (4.3%) | 1 | 1/25 (4%) | 1 |
GASTROINTESTINAL:: Flatulence | 1/23 (4.3%) | 1 | 3/25 (12%) | 3 |
GASTROINTESTINAL:: Gastrointestinal-Other (Specify,_____) | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
GASTROINTESTINAL:: Mouth dryness | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
GASTROINTESTINAL:: Nausea | 13/23 (56.5%) | 34 | 12/25 (48%) | 19 |
GASTROINTESTINAL:: Stomatitis/pharyngitis (oral/pharyngeal mucositis) | 7/23 (30.4%) | 18 | 8/25 (32%) | 13 |
GASTROINTESTINAL:: Taste disturbance (dysgeusia) | 6/23 (26.1%) | 11 | 10/25 (40%) | 17 |
GASTROINTESTINAL:: Vomiting | 10/23 (43.5%) | 17 | 7/25 (28%) | 8 |
GASTROINTESTINAL:: Mucositis due to radiation | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
GASTROINTESTINAL:: Nausea | 0/23 (0%) | 0 | 12/25 (48%) | 19 |
HEMORRHAGE:: Rectal bleeding/hematochezia | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
General disorders | ||||
CONSTITUTIONAL SYMPTOMS:: Fatigue (lethargy, malaise, asthenia) | 18/23 (78.3%) | 42 | 21/25 (84%) | 56 |
CONSTITUTIONAL SYMPTOMS:: Fever (in the absence of neutropenia, where neutropenia is defined as AGC< | 6/23 (26.1%) | 13 | 4/25 (16%) | 5 |
CONSTITUTIONAL SYMPTOMS:: Rigors, chills | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
CONSTITUTIONAL SYMPTOMS:: Weight loss | 3/23 (13%) | 3 | 3/25 (12%) | 3 |
PAIN:: Chest pain (non-cardiac and non-pleuritic) | 4/23 (17.4%) | 4 | 0/25 (0%) | 0 |
Immune system disorders | ||||
ALLERGY/IMMUNOLOGY:: Allergic reaction/hypersensitivity (including drug fever) | 0/23 (0%) | 0 | 2/25 (8%) | 3 |
ALLERGY/IMMUNOLOGY:: Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip) | 8/23 (34.8%) | 9 | 3/25 (12%) | 3 |
ALLERGY/IMMUNOLOGY:: Allergy-Other (Specify,_____) | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
Infections and infestations | ||||
INFECTION/FEBRILE NEUTROPENIA:: Catheter-related infection | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
INFECTION/FEBRILE NEUTROPENIA:: | 3/23 (13%) | 3 | 2/25 (8%) | 2 |
INFECTION/FEBRILE NEUTROPENIA:: | 1/23 (4.3%) | 1 | 1/25 (4%) | 1 |
INFECTION/FEBRILE NEUTROPENIA:: Infection without neutropenia | 4/23 (17.4%) | 7 | 5/25 (20%) | 6 |
INFECTION/FEBRILE NEUTROPENIA:: Infection/Febrile Neutropenia-Other (Specify,____) | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
Investigations | ||||
HEPATIC:: Alkaline phosphatase | 7/23 (30.4%) | 13 | 2/25 (8%) | 2 |
HEPATIC:: Bilirubin | 5/23 (21.7%) | 14 | 3/25 (12%) | 7 |
HEPATIC:: SGOT (AST) (serum glutamic oxaloacetic transaminase) | 7/23 (30.4%) | 11 | 1/25 (4%) | 1 |
HEPATIC:: SGPT (ALT) (serum glutamic pyruvic transaminase) | 5/23 (21.7%) | 6 | 2/25 (8%) | 2 |
METABOLIC/LABORATORY:: CPK (creatine phosphokinase) | 1/23 (4.3%) | 1 | 1/25 (4%) | 1 |
BLOOD/BONE MARROW:: Hemoglobin | 0/23 (0%) | 0 | 20/25 (80%) | 72 |
METABOLIC/LABORATORY:: Hyperuricemia | 1/23 (4.3%) | 1 | 2/25 (8%) | 3 |
Metabolism and nutrition disorders | ||||
HEPATIC:: Hypoalbuminemia | 16/23 (69.6%) | 36 | 12/25 (48%) | 40 |
METABOLIC/LABORATORY:: Bicarbonate | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
METABOLIC/LABORATORY:: Hypercalcemia | 1/23 (4.3%) | 2 | 1/25 (4%) | 1 |
METABOLIC/LABORATORY:: Hyperglycemia | 10/23 (43.5%) | 26 | 11/25 (44%) | 23 |
METABOLIC/LABORATORY:: Hyperkalemia | 2/23 (8.7%) | 2 | 3/25 (12%) | 5 |
METABOLIC/LABORATORY:: Hypermagnesemia | 3/23 (13%) | 5 | 3/25 (12%) | 4 |
METABOLIC/LABORATORY:: Hypernatremia | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
METABOLIC/LABORATORY:: Hypocalcemia | 7/23 (30.4%) | 20 | 7/25 (28%) | 21 |
METABOLIC/LABORATORY:: Hypoglycemia | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
METABOLIC/LABORATORY:: Hypomagnesemia | 8/23 (34.8%) | 18 | 4/25 (16%) | 6 |
METABOLIC/LABORATORY:: Hyponatremia | 14/23 (60.9%) | 36 | 15/25 (60%) | 26 |
METABOLIC/LABORATORY:: Hypophosphatemia | 3/23 (13%) | 9 | 1/25 (4%) | 1 |
METABOLIC/LABORATORY:: Hypokalemia | 5/23 (21.7%) | 6 | 3/25 (12%) | 6 |
Musculoskeletal and connective tissue disorders | ||||
MUSCULOSKELETAL:: Muscle weakness (not due to neuropathy) | 1/23 (4.3%) | 1 | 5/25 (20%) | 7 |
PAIN:: Arthralgia (joint pain) | 6/23 (26.1%) | 9 | 6/25 (24%) | 10 |
PAIN:: Bone pain | 3/23 (13%) | 5 | 4/25 (16%) | 5 |
PAIN:: Myalgia (muscle pain) | 7/23 (30.4%) | 22 | 8/25 (32%) | 12 |
Nervous system disorders | ||||
NEUROLOGY:: Ataxia (incoordination) | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
NEUROLOGY:: Confusion | 1/23 (4.3%) | 2 | 1/25 (4%) | 1 |
NEUROLOGY:: Depressed level of consciousness | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
NEUROLOGY:: Dizziness/lightheadedness | 5/23 (21.7%) | 5 | 3/25 (12%) | 3 |
NEUROLOGY:: Extrapyramidal/involuntary movement/restlessness | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
NEUROLOGY:: Insomnia | 4/23 (17.4%) | 4 | 3/25 (12%) | 3 |
NEUROLOGY:: Mood alteration-depression | 2/23 (8.7%) | 2 | 2/25 (8%) | 2 |
NEUROLOGY:: Neuropathy-sensory | 6/23 (26.1%) | 7 | 8/25 (32%) | 11 |
NEUROLOGY:: Seizure(s) | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
NEUROLOGY:: Syncope (fainting | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
NEUROLOGY:: Vertigo | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
PAIN:: Neuropathic pain (e.g., jaw pain, neurologic pain, phantom limb pain, post-infectious neuralg | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
PAIN:: Pain-Other (Specify,___) | 9/23 (39.1%) | 11 | 2/25 (8%) | 2 |
PAIN:: Headache | 5/23 (21.7%) | 5 | 5/25 (20%) | 6 |
NEUROLOGY:: Mood alteration-anxiety, agitation | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
Renal and urinary disorders | ||||
RENAL/GENITOURINARY:: Creatinine | 2/23 (8.7%) | 2 | 2/25 (8%) | 3 |
RENAL/GENITOURINARY:: Urinary frequency/urgency | 2/23 (8.7%) | 2 | 1/25 (4%) | 1 |
HEMORRHAGE:: Hematuria (in the absence of vaginal bleeding) | 0/23 (0%) | 0 | 1/25 (4%) | 2 |
RENAL/GENITOURINARY:: Dysuria (painful urination) | 0/23 (0%) | 0 | 2/25 (8%) | 2 |
RENAL/GENITOURINARY:: Urinary retention | 0/23 (0%) | 0 | 2/25 (8%) | 2 |
Reproductive system and breast disorders | ||||
PAIN:: Abdominal pain or cramping | 5/23 (21.7%) | 5 | 6/25 (24%) | 8 |
PAIN:: Pelvic pain | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||||
HEMORRHAGE:: Epistaxis | 2/23 (8.7%) | 2 | 0/25 (0%) | 0 |
PULMONARY:: Cough | 9/23 (39.1%) | 9 | 3/25 (12%) | 3 |
PULMONARY:: Dyspnea (shortness of breath) | 9/23 (39.1%) | 10 | 7/25 (28%) | 9 |
PULMONARY:: Pleural effusion (non-malignant) | 2/23 (8.7%) | 2 | 2/25 (8%) | 5 |
PULMONARY:: Pulmonary-Other (Specify,___) | 2/23 (8.7%) | 3 | 0/25 (0%) | 0 |
PULMONARY:: Voice changes/stridor/larynx (e.g., hoarseness, loss of voice, laryngitis) | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
PULMONARY:: Hypoxia | 2/23 (8.7%) | 2 | 1/25 (4%) | 1 |
Skin and subcutaneous tissue disorders | ||||
DERMATOLOGY/SKIN:: Alopecia | 8/23 (34.8%) | 9 | 8/25 (32%) | 10 |
DERMATOLOGY/SKIN:: Dermatology/Skin-Other (Specify,_____) | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
DERMATOLOGY/SKIN:: Dry skin | 3/23 (13%) | 3 | 1/25 (4%) | 1 |
DERMATOLOGY/SKIN:: Erythema multiforme (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis) | 1/23 (4.3%) | 1 | 1/25 (4%) | 1 |
DERMATOLOGY/SKIN:: Flushing | 4/23 (17.4%) | 7 | 1/25 (4%) | 2 |
DERMATOLOGY/SKIN:: Hand-foot skin reaction | 4/23 (17.4%) | 5 | 3/25 (12%) | 3 |
DERMATOLOGY/SKIN:: Injection site reaction | 1/23 (4.3%) | 1 | 5/25 (20%) | 5 |
DERMATOLOGY/SKIN:: Nail changes | 6/23 (26.1%) | 9 | 8/25 (32%) | 8 |
DERMATOLOGY/SKIN:: Radiation dermatitis | 1/23 (4.3%) | 1 | 0/25 (0%) | 0 |
DERMATOLOGY/SKIN:: Rash/desquamation | 4/23 (17.4%) | 4 | 3/25 (12%) | 4 |
DERMATOLOGY/SKIN:: Bruising (in absence of grade 3 or 4 thrombocytopenia) | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
DERMATOLOGY/SKIN:: Pruritus | 0/23 (0%) | 0 | 2/25 (8%) | 2 |
DERMATOLOGY/SKIN:: Wound-non-infectious | 0/23 (0%) | 0 | 1/25 (4%) | 1 |
Limitations/Caveats
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 | Susan E. Bates, M.D. |
---|---|
Organization | National Cancer Institute, National Institutes of Health |
Phone | 301-402-1357 |
BatesS@mail.nih.gov |
- 030284
- 03-C-0284
- 030284
- NCT00072202