Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2011-02500 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| CDR0000700997 | |||
| UPCI 10-115 | |||
| UPCI-10-115 | |||
| 8808 | Other Identifier | University of Pittsburgh Cancer Institute (UPCI) | |
| 8808 | Other Identifier | CTEP | |
| N01CM00100 | U.S. NIH Grant/Contract | View source | |
| P30CA047904 | U.S. NIH Grant/Contract | View source | |
| U01CA062490 | U.S. NIH Grant/Contract | View source | |
| U01CA062502 | U.S. NIH Grant/Contract | View source | |
| U01CA062505 | U.S. NIH Grant/Contract | View source | |
| U01CA069856 | U.S. NIH Grant/Contract | View source | |
| U01CA070095 | U.S. NIH Grant/Contract | View source | |
| U01CA099168 | U.S. NIH Grant/Contract | View source | |
| UM1CA186690 | U.S. NIH Grant/Contract | View source | |
| UM1CA186691 | U.S. NIH Grant/Contract | View source | |
| UM1CA186709 | U.S. NIH Grant/Contract | View source | |
| UM1CA186716 | U.S. NIH Grant/Contract | View source | |
| UM1CA186717 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Abbott | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This phase I trial studies the side effects and the best dose of veliparib when given together with paclitaxel and carboplatin in treating patients with solid tumors that are metastatic or cannot be removed by surgery and liver or kidney dysfunction. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving veliparib together with paclitaxel and carboplatin may kill more tumor cells.
PRIMARY OBJECTIVES:
I. To determine the pharmacokinetics and pharmacodynamics of ABT-888 (veliparib) in patients with varying degrees of renal or hepatic dysfunction.
II. To determine the maximum tolerated dose (MTD) of ABT-888 in combination with carboplatin and paclitaxel for patients with varying degrees of liver or kidney dysfunction.
III. To provide dosing recommendations for ABT-888 in combination with carboplatin and paclitaxel based on degree of hepatic and renal impairment.
SECONDARY OBJECTIVES:
I. To define the dose-limiting toxicity (DLT) and other toxicities associated with the use of this combination in patients with varying degrees of renal or hepatic dysfunction.
II. To evaluate the pharmacokinetic parameters of ABT-888, carboplatin, and paclitaxel when administered as a combination in patients with varying degrees of renal or hepatic dysfunction.
III. To evaluate the pharmacodynamic measurement of poly-ADP-ribosylated (PAR) and platinum adducts in tumor cells associated with the use of this combination in patients with varying degrees of renal or hepatic dysfunction.
OUTLINE: This is a dose-escalation study of veliparib.
Patients receive veliparib* orally (PO) twice daily (BID) on days 1-7 and paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 3. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
NOTE: * All patients receive a single dose of veliparib PO on day -6 before course 1 (except patients with very severe renal dysfunction who receive veliparib on day -5 or -6 to coincide with a dialysis day).
After completion of study treatment, patients are followed up for 4 weeks.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (veliparib, paclitaxel, carboplatin) | Experimental | Patients receive veliparib* PO BID on days 1-7 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 3. Courses repeat every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. NOTE: * All patients receive a single dose of veliparib PO on day -6 before course 1 (except patients with very severe renal dysfunction who receive veliparib on day -5 or -6 to coincide with a dialysis day). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Carboplatin | Drug | Given IV |
|
| Measure | Description | Time Frame |
|---|---|---|
| PK parameters of veliparib | Standard quantitative and graphical statistical summaries of the derived PK parameters (e.g. area under curve and clearance) will be produced for each organ function cohort. The effect of dysfunction on pharmacokinetics will be explored by comparing each pharmacokinetic parameter across all cohorts using one-way analysis (analysis of variance) or Kruskal-Wallis test. The level of each protein will be compared between responders and non-responders using the Wilcoxon signed rank test. | Day -6 and 3 of course 1 after veliparib dosing |
| MTD of veliparib in combination with carboplatin and paclitaxel, determined according to incidence of DLT as graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 4.0 | 21 days |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of toxicities as assessed by NCI CTCAE v4.0 | The maximum grade of toxicity for each category of interest will be recorded for each patient and the summary results will be tabulated by category, grade and dose level. Severe and life-threatening toxicities and adverse event-related deaths (>= grade 3) will be described on a patient-by-patient basis and will include any relevant baseline data. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in PAR levels | Descriptive statistics (mean, standard deviation, median, range) for measurements of PAR levels will provided with 95% confidence intervals (CIs). When sample size permits, a formal statistical test using the Wilcoxon signed rank test will be used to compare the post treatment PAR levels to the baseline levels. When feasible, the level will be compared between responders and non-responders using the Wilcoxon signed rank test. |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Hussein A Tawbi | University of Pittsburgh Cancer Institute (UPCI) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| City of Hope Comprehensive Cancer Center | Duarte | California | 91010 | United States | ||
| University of California Davis Comprehensive Cancer Center |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Laboratory Biomarker Analysis | Other | Correlative studies |
|
| Paclitaxel | Drug | Given IV |
|
|
| Pharmacological Study | Other | Correlative studies |
|
| Veliparib | Drug | Given PO |
|
|
| Up to 4 weeks after completion of study treatment |
| Response rate as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 | Responses will be tabulated by disease diagnosis and by dose level. 95% confidence limits will also be reported on the response rates. | Up to 4 weeks after completion of study treatment |
| Incidence of stable disease as assessed by RECIST version 1.1 | Incidence of stable disease will be tabulated by disease diagnosis and by dose level. | Up to 4 weeks after completion of study treatment |
| Time to progression | Displayed for all patients and for patients who have responded; no formal statistical analysis is planned. | Up to 4 weeks after completion of study treatment |
| Baseline to up to 4 weeks |
| Change in gamma-H2AX levels | Descriptive statistics (mean, standard deviation, median, range) for measurements of gamma-H2AX levels will provided with 95% CIs. When sample size permits, a formal statistical test using the Wilcoxon signed rank test will be used to compare the post treatment PAR levels to the baseline levels. When feasible, the level will be compared between responders and non-responders using the Wilcoxon signed rank test. | Baseline to up to 4 weeks |
| Sacramento |
| California |
| 95817 |
| United States |
| City of Hope South Pasadena | South Pasadena | California | 91030 | United States |
| Moffitt Cancer Center | Tampa | Florida | 33612 | United States |
| Emory University Hospital/Winship Cancer Institute | Atlanta | Georgia | 30322 | United States |
| Johns Hopkins University/Sidney Kimmel Cancer Center | Baltimore | Maryland | 21287 | United States |
| Dana-Farber Cancer Institute | Boston | Massachusetts | 02215 | United States |
| Wayne State University/Karmanos Cancer Institute | Detroit | Michigan | 48201 | United States |
| Rutgers Cancer Institute of New Jersey | New Brunswick | New Jersey | 08903 | United States |
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
| Montefiore Medical Center-Weiler Hospital | The Bronx | New York | 10461 | United States |
| Montefiore Medical Center - Moses Campus | The Bronx | New York | 10467 | United States |
| Case Western Reserve University | Cleveland | Ohio | 44106 | United States |
| Penn State Milton S Hershey Medical Center | Hershey | Pennsylvania | 17033-0850 | United States |
| University of Pittsburgh Cancer Institute (UPCI) | Pittsburgh | Pennsylvania | 15232 | United States |
| UT MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| University of Wisconsin Carbone Cancer Center - University Hospital | Madison | Wisconsin | 53792 | United States |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D009382 | Neoplasms, Unknown Primary |
| D016889 | Endometrial Neoplasms |
| D004938 | Esophageal Neoplasms |
| D017093 | Liver Failure |
| D008175 | Lung Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D013736 | Testicular Neoplasms |
| D008545 | Melanoma |
| D009362 | Neoplasm Metastasis |
| D010051 | Ovarian Neoplasms |
| D051437 | Renal Insufficiency |
| D002295 | Carcinoma, Transitional Cell |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D014594 | Uterine Neoplasms |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D014591 | Uterine Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| D048550 | Hepatic Insufficiency |
| D008107 | Liver Diseases |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D004701 | Endocrine Gland Neoplasms |
| D005834 | Genital Neoplasms, Male |
| D005832 | Genital Diseases, Male |
| D052801 | Male Urogenital Diseases |
| D004700 | Endocrine System Diseases |
| D013733 | Testicular Diseases |
| D006058 | Gonadal Disorders |
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
Not provided
Not provided
| ID | Term |
|---|---|
| D016190 | Carboplatin |
| D017239 | Paclitaxel |
| D013660 | Taxes |
| C521013 | veliparib |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D004467 | Economics |
| D004472 | Health Care Economics and Organizations |
Not provided
Not provided