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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01145430
First received: June 15, 2010
Last updated: March 26, 2014
Last verified: February 2014
  Purpose

This phase I trial is studying the side effects and the best dose of veliparib when given together with pegylated liposomal doxorubicin hydrochloride in patients with recurrent ovarian cancer, fallopian tube cancer, or primary peritoneal cancer or metastatic breast cancer. 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 or by stopping them from dividing. Giving veliparib together with liposomal doxorubicin hydrochloride may kill more tumor cells.


Condition Intervention Phase
Estrogen Receptor-negative Breast Cancer
HER2-negative Breast Cancer
Male Breast Cancer
Progesterone Receptor-negative Breast Cancer
Recurrent Breast Cancer
Recurrent Fallopian Tube Cancer
Recurrent Ovarian Epithelial Cancer
Recurrent Primary Peritoneal Cavity Cancer
Stage IV Breast Cancer
Triple-negative Breast Cancer
Drug: veliparib
Drug: pegylated liposomal doxorubicin hydrochloride
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of ABT-888, PARP Inhibitor, and Pegylated Liposomal Doxorubicin (PLD) in Recurrent Gynecologic Cancer and Breast Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Recommended Phase II dose, 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: Time from first treatment day until objective or symptomatic progression, assessed up to 3 years ] [ Designated as safety issue: No ]
    Will be assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formulae.

  • Overall survival [ Time Frame: Time from first treatment day until death or until last follow-up, assessed up to 3 years ] [ Designated as safety issue: No ]
    Will be assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formulae.

  • 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 ] [ Designated as safety issue: Yes ]
    Will be tabulated. Exact 95% confidence intervals around the toxicity proportions will be calculated to assess the precision of the obtained estimates.


Estimated Enrollment: 58
Study Start Date: June 2010
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (veliparib and liposomal doxorubicin hydrochloride)
Patients 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.
Drug: veliparib
Given PO
Other Name: ABT-888
Drug: pegylated liposomal doxorubicin hydrochloride
Given IV
Other Names:
  • CAELYX
  • Dox-SL
  • DOXIL
  • doxorubicin hydrochloride liposome
  • LipoDox
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 =< 1.5mg/dL
  • Total bilirubin =< 1.5x 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01145430

Locations
United States, New York
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10467-2490
Contact: Joseph A. Sparano    718-904-2555    jsparano@montefiore.org   
Principal Investigator: Joseph A. Sparano         
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Dawn L. Hershman    212-305-1945    dlh23@columbia.edu   
Principal Investigator: Dawn L. Hershman         
Mount Sinai Medical Center Recruiting
New York, New York, United States, 10029
Contact: George Raptis    212-241-2298    george.raptis@mssm.edu   
Principal Investigator: George Raptis         
New York University Clinical Cancer Center Recruiting
New York, New York, United States, 10016-4760
Contact: Bhavana Pothuri    212-731-5345    bhavana.pothuri@nyumc.org   
Principal Investigator: Bhavana Pothuri         
Weill Medical College of Cornell University Recruiting
New York, New York, United States, 10065
Contact: Linda T. Vahdat    212-821-0644    ltv2001@med.cornell.edu   
Principal Investigator: Linda T. Vahdat         
Sponsors and Collaborators
Investigators
Principal Investigator: Bhavana Pothuri Montefiore Medical Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01145430     History of Changes
Other Study ID Numbers: NCI-2012-03161, NCI-2012-03161, AECM-000248, 10-01206, 8475, P30CA013330, N01CM62204
Study First Received: June 15, 2010
Last Updated: March 26, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Breast Neoplasms, Male
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Fallopian Tube Diseases
Adnexal Diseases
Genital Diseases, Female
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Ovarian Diseases
Endocrine System Diseases
Gonadal Disorders
Doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 26, 2014