Ignite Creation Date:
2025-12-25 @ 3:20 AM
Ignite Modification Date:
2025-12-26 @ 1:58 AM
Study NCT ID:
NCT00740805
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-11-06
First Post:
2008-08-22
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Veliparib, Cyclophosphamide, and Doxorubicin Hydrochloride in Treating Patients With Metastatic or Unresectable Solid Tumors or Non-Hodgkin Lymphoma
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase I Study of ABT-888 in Combination With Cyclophosphamide in Solid Tumors or Non-Hodgkin Lymphoma
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I trial studies the side effects and best dose of veliparib, cyclophosphamide, and doxorubicin hydrochloride when given together in treating patients solid tumors or non-Hodgkin lymphoma that has spread to other areas of the body or cannot be removed by surgery. Veliparib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide and doxorubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving veliparib, cyclophosphamide, and doxorubicin hydrochloride may kill more cancer cells.
Detailed Description:
PRIMARY OBJECTIVES:
I. Identify the maximally tolerated dose (MTD) and dose limiting toxicity (DLT) of cyclophosphamide when combined with escalating doses of ABT-888 (veliparib).
II. Identify the maximally tolerated dose (MTD) and dose limiting toxicity (DLT) of cyclophosphamide and doxorubicin (doxorubicin hydrochloride) when combined with escalating doses of ABT-888.
SECONDARY OBJECTIVES:
I. Evaluate any effect of ABT-888 on the systemic clearance of parent cyclophosphamide and the dose normalized area under the curve (AUC) of 4-hydroxy (4-OH) cyclophosphamide when used in combination, using historical single-agent cyclophosphamide and 4-OH data.
II. Evaluate any effect of cyclophosphamide administration on the systemic pharmacokinetics of ABT-888 and its primary metabolite A-925088 (M8), by comparing pharmacokinetic (PK) parameters of ABT-888 on day 1 (before cyclophosphamide) and day 3 (with cyclophosphamide administration); PK samples for analysis will not be collected from patients enrolled after 2/15/2012.
III. Evaluate inhibition of poly (adenosine diphosphate \[ADP\] ribose) polymerase (PARP) using an immunoassay designed to measure PAR levels in baseline and on-study peripheral blood mononuclear cells (PBMC) samples; PBMC samples for PAR analysis will not be collected from patients enrolled after 2/15/2012.
IV. Evaluate gamma H2A histone family, member X (H2AX) at baseline and on-study circulating tumor cell samples to evaluate the point of maximal deoxyribonucleic acid (DNA) damage from the combination of cyclophosphamide and doxorubicin with ABT-888.
OUTLINE: This is a dose-escalation study of veliparib and cyclophosphamide.
GROUP I: Patients receive veliparib orally (PO) every 12 hours on days 1-4 and cyclophosphamide intravenously (IV) over 60 minutes on day 3.
GROUP II: Patients receive veliparib PO every 12 hours on days 1-4, cyclophosphamide IV over 60 minutes on day 3, and doxorubicin hydrochloride IV over 15 minutes on day 3.
GROUP III: Patients receive veliparib PO every 12 hours on days 1-7, cyclophosphamide IV over 60 minutes on day 1, and doxorubicin hydrochloride IV over 15 minutes on day 1.
GROUP IV: Patients receive veliparib PO every 12 hours on days 1-14, cyclophosphamide IV over 60 minutes on day 1, and doxorubicin hydrochloride over 15 minutes on day 1.
In all groups, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 4 weeks.
I. Identify the maximally tolerated dose (MTD) and dose limiting toxicity (DLT) of cyclophosphamide when combined with escalating doses of ABT-888 (veliparib).
II. Identify the maximally tolerated dose (MTD) and dose limiting toxicity (DLT) of cyclophosphamide and doxorubicin (doxorubicin hydrochloride) when combined with escalating doses of ABT-888.
SECONDARY OBJECTIVES:
I. Evaluate any effect of ABT-888 on the systemic clearance of parent cyclophosphamide and the dose normalized area under the curve (AUC) of 4-hydroxy (4-OH) cyclophosphamide when used in combination, using historical single-agent cyclophosphamide and 4-OH data.
II. Evaluate any effect of cyclophosphamide administration on the systemic pharmacokinetics of ABT-888 and its primary metabolite A-925088 (M8), by comparing pharmacokinetic (PK) parameters of ABT-888 on day 1 (before cyclophosphamide) and day 3 (with cyclophosphamide administration); PK samples for analysis will not be collected from patients enrolled after 2/15/2012.
III. Evaluate inhibition of poly (adenosine diphosphate \[ADP\] ribose) polymerase (PARP) using an immunoassay designed to measure PAR levels in baseline and on-study peripheral blood mononuclear cells (PBMC) samples; PBMC samples for PAR analysis will not be collected from patients enrolled after 2/15/2012.
IV. Evaluate gamma H2A histone family, member X (H2AX) at baseline and on-study circulating tumor cell samples to evaluate the point of maximal deoxyribonucleic acid (DNA) damage from the combination of cyclophosphamide and doxorubicin with ABT-888.
OUTLINE: This is a dose-escalation study of veliparib and cyclophosphamide.
GROUP I: Patients receive veliparib orally (PO) every 12 hours on days 1-4 and cyclophosphamide intravenously (IV) over 60 minutes on day 3.
GROUP II: Patients receive veliparib PO every 12 hours on days 1-4, cyclophosphamide IV over 60 minutes on day 3, and doxorubicin hydrochloride IV over 15 minutes on day 3.
GROUP III: Patients receive veliparib PO every 12 hours on days 1-7, cyclophosphamide IV over 60 minutes on day 1, and doxorubicin hydrochloride IV over 15 minutes on day 1.
GROUP IV: Patients receive veliparib PO every 12 hours on days 1-14, cyclophosphamide IV over 60 minutes on day 1, and doxorubicin hydrochloride over 15 minutes on day 1.
In all groups, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 4 weeks.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2009-00262 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| CDR0000600234 | None | None | View | |
| 050803 | None | None | View | |
| 050803 | OTHER | Rutgers Cancer Institute of New Jersey | View | |
| 7998 | OTHER | CTEP | View | |
| P30CA072720 | NIH | None | https://reporter.nih.gov/quic… | View |
| U01CA132194 | NIH | None | https://reporter.nih.gov/quic… | View |
| U01CA099118 | NIH | None | https://reporter.nih.gov/quic… | View |
| UM1CA186716 | NIH | None | https://reporter.nih.gov/quic… | View |