Clinical Trials /

Veliparib and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Recurrent Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer or Metastatic Breast Cancer

NCT01145430

Description:

This phase I trial studies the side effects and the best dose of veliparib when given together with pegylated liposomal doxorubicin hydrochloride in treating patients with ovarian cancer, fallopian tube cancer, or primary peritoneal cancer that has come back after a period of improvement, or breast cancer that has spread to other parts of the body. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as liposomal doxorubicin hydrochloride, 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 liposomal doxorubicin hydrochloride may kill more tumor cells.

Related Conditions:
  • Breast Carcinoma
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Veliparib and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Recurrent Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer or Metastatic Breast Cancer
  • Official Title: Phase I Study of ABT-888, PARP Inhibitor, and Pegylated Liposomal Doxorubicin (PLD) in Recurrent Gynecologic Cancer and Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: NCI-2012-03161
  • SECONDARY ID: NCI-2012-03161
  • SECONDARY ID: AECM-000248
  • SECONDARY ID: 10-01206
  • SECONDARY ID: 8475
  • SECONDARY ID: 8475
  • SECONDARY ID: N01CM62204
  • SECONDARY ID: P30CA013330
  • NCT ID: NCT01145430

Conditions

  • Estrogen Receptor Negative
  • HER2/Neu Negative
  • Male Breast Carcinoma
  • Progesterone Receptor Negative
  • Recurrent Breast Carcinoma
  • Recurrent Fallopian Tube Carcinoma
  • Recurrent Ovarian Carcinoma
  • Recurrent Primary Peritoneal Carcinoma
  • Stage IV Breast Cancer AJCC v6 and v7
  • Triple-Negative Breast Carcinoma

Interventions

DrugSynonymsArms
Pegylated Liposomal Doxorubicin HydrochlorideATI-0918, Caelyx, DOX-SL, Doxil, Doxilen, Doxorubicin HCl Liposome, doxorubicin hydrochloride liposome, Duomeisu, Evacet, LipoDox, Liposomal Adriamycin, liposomal doxorubicin hydrochloride, Liposomal-Encapsulated Doxorubicin, Pegylated Doxorubicin HCl Liposome, S-Liposomal Doxorubicin, Stealth Liposomal Doxorubicin, TLC D-99Treatment (veliparib and liposomal doxorubicin hydrochloride)
VeliparibABT-888, PARP-1 inhibitor ABT-888Treatment (veliparib and liposomal doxorubicin hydrochloride)

Purpose

This phase I trial studies the side effects and the best dose of veliparib when given together with pegylated liposomal doxorubicin hydrochloride in treating patients with ovarian cancer, fallopian tube cancer, or primary peritoneal cancer that has come back after a period of improvement, or breast cancer that has spread to other parts of the body. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as liposomal doxorubicin hydrochloride, 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 liposomal doxorubicin hydrochloride may kill more tumor cells.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the recommended Phase II dose of ABT-888 (veliparib) given in combination
      with pegylated liposomal doxorubicin (pegylated liposomal doxorubicin hydrochloride) (PLD -
      40 mg/m2 every 4 weeks) in patients with ovarian or breast cancer.

      SECONDARY OBJECTIVES:

      I. To determine the toxicity profile of the ABT-888 plus PLD combination. II. To determine
      the effects of ABT-888 on the pharmacokinetics of PLD. III. To determine the efficacy of
      ABT-888 plus PLD in ovarian and breast cancer.

      OUTLINE: This is a dose-escalation study of veliparib.

      Patients receive veliparib orally (PO) twice daily (BID) on days 1-14 and pegylated liposomal
      doxorubicin hydrochloride intravenously (IV) over 60 minutes on day 1. Courses repeat every
      28 days in the absence of disease progression or unacceptable toxicity.

      After completion of study therapy, patients are followed up every 3 months for 1 year and
      then every 6 months for 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (veliparib and liposomal doxorubicin hydrochloride)ExperimentalPatients receive veliparib PO BID on days 1-14 and pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Pegylated Liposomal Doxorubicin Hydrochloride
  • Veliparib

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of recurrent or residual epithelial ovarian cancer,
             primary peritoneal carcinoma or fallopian tube carcinoma, OR histologically confirmed
             metastatic breast cancer, that is estrogen receptor (ER)-negative, progesterone
             receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)/neu
             negative (as determined by local pathology laboratory)

          -  Prior chemotherapy:

               -  Ovarian cancer: patients with no prior PLD exposure are eligible after failure of
                  platinum-containing chemotherapy; no more than 2 prior platinum containing
                  regimens is permitted; dose escalating cohorts only: patients already on PLD are
                  also eligible if they are receiving PLD beyond 3 cycles without prohibitive (i.e.
                  no grade 3 or 4) skin or mucosal toxicities, and showing no progressive disease
                  compared to a computed tomography (CT) scan obtained 2 or more months earlier;
                  these patients are eligible in spite of any progression from baseline determined
                  prematurely (i.e., applicable to those patients who are deemed in their best
                  interest to continue to receive PLD after a CT obtained at 2 or 3 months has
                  shown progression from baseline)

                    -  Breast cancer: patients may have received 0-2 prior chemotherapy regimens
                       for metastatic disease; breast cancer patients may not have received prior
                       PLD, and will not be eligible for the expanded cohort A

                    -  Interval between prior chemotherapy and registration for breast and ovarian
                       cancer; there should be at least a 3 week interval between the last
                       chemotherapy regimen and registration, and the patient should have recovered
                       from acute toxicity related to prior therapy (6 weeks if the last regiment
                       included BCNU or mitomycin C)

                    -  Dose escalating cohorts only: patients will be categorized in the following
                       strata based upon prior PLD exposure: Stratum A -patients with ovarian
                       cancer who have had prior PLD exposure and received at least 3 cycles of PLD
                       without prohibitive (i.e. no grade 3 or 4 skin toxicity) and have not had
                       progressive disease; Stratum B: patients with ovarian or breast cancer who
                       have had no prior PLD exposure

          -  Eastern Cooperative Oncology Group (ECOG) performance score 0-2

          -  All potential subjects should be evaluated for whether breast cancer (BRCA)1-2 testing
             is medically appropriate; individuals who have a 10% or higher risk of having a
             BRCA1-2 mutation (Myriad tables at www.myriad.com) are encouraged (but not required)
             to have mutation testing and results known; information regarding mutation status
             (positive [including specific mutation], negative, or unknown) and projected risk of
             having a mutation (as determined by Myriad tables) will be collected at the time of
             diagnosis

          -  Non-measurable and/or measurable disease by Response Evaluation Criteria in Solid
             Tumors (RECIST) criteria, or abnormal cancer antigen (CA)-125 to levels (in patients
             with ovarian cancer) at least 1.5 x normal documented by two independent measurements
             at least 4 weeks apart

          -  Ability to give voluntary informed consent and to comply with treatment and required
             tests

          -  Ability to tolerate oral medications

          -  Female subjects age >= 18 years (males with breast cancer are eligible)

          -  Absolute neutrophil count >= 1500/mL

          -  Platelets >= 100,000/mL

          -  Creatinine =< 1.5 mg/dL

          -  Total bilirubin =< 1.5 x institutional upper limit of normal

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x
             institutional upper limit of normal (=< 5 x institutional upper limit of normal if
             evidence of liver metastasis)

          -  Left ventricular ejection fraction at or above institutional lower limit of normal
             (obtained within 8 weeks of registration by multigated acquisition [MUGA] scan or
             echocardiogram; the same test performed at baseline should be repeated after every 3
             cycles of therapy)

          -  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

        Exclusion Criteria:

          -  Known central nervous system (CNS) metastases with active symptoms, or requiring
             anticonvulsive medications, or steroids

          -  Prior chemotherapy (except PLD in Dose Escalation Cohorts only) or any investigational
             agent within 3 weeks prior to registration

          -  Prior radiation therapy to whole pelvis or greater amount of marrow-forming bone

          -  Prior or current non-gynecologic or non-breast malignancy within 5 years except
             non-melanoma skin cancer

          -  Patients with active severe infection; known infection with human immunodeficiency
             virus (HIV), hepatitis B virus, hepatitis C virus, or severe concurrent illness

          -  Patients with any non-malignant intercurrent illness (e.g. cardiovascular, pulmonary,
             central nervous system disease) which is either poorly controlled with currently
             available treatment, or which is of such severity that the investigators deem it
             unwise to enter the patient on protocol

          -  Patients with history of seizure disorder requiring antiepileptics who have had a
             seizure episode within the last 6 months

          -  Pregnant (positive pregnancy test) or lactating; unwillingness to use effective means
             of contraception in subjects with child-bearing potential

          -  Evidence of complete or partial bowel obstruction or other unable to take oral
             medications
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended Phase II dose of veliparib, based on incidence of dose limiting toxicity, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time Frame:Up to 28 days
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Frequency of subjects experiencing toxicities in each stratum, assessed and graded according to terminology in the Cancer Therapy Evaluation Program (CTEP) version 4.0 of the CTCAE
Time Frame:Up to 3 years
Safety Issue:
Description:Will be tabulated. Exact 95% confidence intervals around the toxicity proportions will be calculated to assess the precision of the obtained estimates.
Measure:Overall survival
Time Frame:Time from first treatment day until death or until last follow-up, assessed up to 3 years
Safety Issue:
Description:Will be assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formulae.
Measure:Progression-free survival
Time Frame:Time from first treatment day until objective or symptomatic progression, assessed up to 3 years
Safety Issue:
Description:Will be assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formulae.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:National Cancer Institute (NCI)

Last Updated

December 21, 2017