Veliparib, Cyclophosphamide, and Doxorubicin Hydrochloride in Treating Patients With Metastatic or Unresectable Solid Tumors or Non-Hodgkin Lymphoma

NCT00740805 | Active Not Recruiting Phase 1 DMC

• 8 other identifiers: NCI-2009-00262CDR00006002340508037998P30CA072720U01CA132194U01CA099118UM1CA186716
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

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.

Conditions

Ann Arbor Stage IV Non-Hodgkin Lymphoma; Solid Neoplasm; Ann Arbor Stage III Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• MTD, defined as the dose level that no more than 2/6 or 1/3 patients experience DLT and at least 2/3 or 3/6 patients treated with next higher dose level will have had DLT

  Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  21 days

Secondary Outcomes (2)

• Change in pharmacokinetic parameters

  Day 1, course 1 to day 1, course 2

• Change in gammaH2AX levels (quantification of the time point of maximal DNA damage)

  Baseline to up to day 14

Study Arms (1)

Treatment (veliparib, cyclophosphamide, doxorubicin)

EXPERIMENTAL

GROUP I: Patients receive veliparib PO every 12 hours on days 1-4 and cyclophosphamide 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.

Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Veliparib

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518, B-518, B518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR 138719, WR- 138719, WR-138719, WR138719

Treatment (veliparib, cyclophosphamide, doxorubicin)

Doxorubicin Hydrochloride DRUG

Given IV

Also known as: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin HCl, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, FI106, hydroxydaunorubicin, Rubex

Treatment (veliparib, cyclophosphamide, doxorubicin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (veliparib, cyclophosphamide, doxorubicin)

Pharmacological Study OTHER

Correlative studies

Treatment (veliparib, cyclophosphamide, doxorubicin)

Veliparib DRUG

Given PO

Also known as: ABT 888, ABT-888, ABT888, PARP-1 inhibitor ABT-888

Treatment (veliparib, cyclophosphamide, doxorubicin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective; patients with either solid tumors or non-Hodgkin's lymphoma are eligible
• At the recommended Phase II dose level, an additional 6 to 12 patients in each group with the following criteria will be enrolled: documented breast cancer (BRCA)1/BRC2 mutation, triple-negative breast cancer defined as estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor (HER)2-negative, or patients who would benefit from a cyclophosphamide-based regimen
• On the schedule of ABT-888 given for 7 or 14 days, only patients with metastatic breast cancer will be enrolled
• Patients must be \>= 4 weeks since prior chemotherapy or radiation therapy (\>= 6 weeks if the last regimen included carmustine \[BCNU\] or mitomycin C); patients previously treated with cyclophosphamide should not be necessarily excluded
• Patients with non-Hodgkin's lymphoma that is amenable to hematopoietic stem cell transplantation with curative intent may participate only if stem cell transplant is refused or is not indicated
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Life expectancy of greater than 2 months
• Hemoglobin \>= 9.0 g/dL
• Absolute neutrophil count (ANC) \>= 1,500/uL
• Platelets \>= 100,000/uL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X institutional upper limit of normal (ULN), =\< 5 x ULN if known hepatic metastases
• Creatinine within normal institutional limits OR creatinine clearance \>= 60 ml/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• Prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time (PTT) =\< 1.2 X institutional ULN
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

You may not qualify if:

• Concurrent administration of any other investigational agent(s)
• Prior high-dose therapy requiring hematopoietic stem cell transplantation
• Prior anti-cancer treatments involving radioactive pharmaceuticals
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ABT-888 and/or cyclophosphamide
• Patients receiving any medications or substances that are strong inhibitors or strong inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP 3A4), cytochrome P450, family 2, subfamily B, polypeptide 6 (2B6), cytochrome P450, family 2, subfamily C, polypeptide 9 (2C9) or cytochrome P450, family 2, subfamily C, polypeptide 19 (2C19) are prohibited; at the time of screening, if the patient is currently receiving any of the listed prohibited medication(s), the medication(s) must be discontinued for a period of no less than 7 days prior to administration of the first dose of study medication in order for the patient to meet study eligibility except for the following substance where the washout should be 6 months: amiodarone
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; New York Heart Association (NYHA) grade II or greater congestive heart failure
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ABT-888; these potential risks may also apply to other agents used in this study
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated; NOTE: HIV seropositive patients not receiving combination antiretroviral therapy who have cluster of differentiation (CD)4 cells \>= 350/mm\^3, no opportunistic infections and meet all eligibility criteria may participate in this study
• Any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain ABT-888 capsules
• Patients with gastrointestinal conditions that might predispose for drug intolerability or poor drug absorption (e.g., inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, malabsorption syndrome, active peptic ulcer disease) are excluded; subjects with ulcerative colitis, inflammatory bowel disease, or a partial or complete small bowel obstruction are also excluded
• Patients with active central nervous system (CNS) metastases are excluded
• Patients with CNS metastases that have been treated must be off steroid treatment for \> 3 months, be asymptomatic and off steroid treatment prior to study enrollment
• Patients that have symptoms to suggest CNS metastases should have a brain magnetic resonance imaging (MRI) within 28 days of enrollment to confirm the absence of CNS metastases; contrast computed tomography (CT) is acceptable for patients who are unable to undergo a brain MRI
• Patients with active seizure or a history of active seizure
• Any other medical, social, or psychological condition that may significantly affect safety and/or compliance

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

MeSH Terms

Interventions

Cyclophosphamide; Doxorubicin; veliparib

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Mark N Stein

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2008
• First Posted: August 25, 2008
• Study Start: August 18, 2008
• Primary Completion: September 3, 2021
• Study Completion (Estimated): October 22, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-02

Locations

US (1)