Veliparib, Topotecan Hydrochloride, and Filgrastim or Pegfilgrastim in Treating Patients With Persistent or Recurrent Cervical Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01266447
First received: December 23, 2010
Last updated: August 5, 2015
Last verified: July 2015
  Purpose

This phase II clinical trial is studying the how well veliparib, topotecan hydrochloride, and filgrastim or pegfilgrastim work in treating patients with persistent or recurrent cervical 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 topotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by blocking them from dividing. Giving veliparib with chemotherapy may kill more tumor cells. Filgrastim or pegfilgrastim may cause the body to make more blood cells and help it recover from the side effects of chemotherapy.


Condition Intervention Phase
Cervical Adenocarcinoma
Cervical Adenosquamous Carcinoma
Cervical Small Cell Carcinoma
Cervical Squamous Cell Carcinoma
Recurrent Cervical Carcinoma
Stage III Cervical Cancer
Stage IVA Cervical Cancer
Stage IVB Cervical Cancer
Biological: Filgrastim
Other: Laboratory Biomarker Analysis
Biological: Pegfilgrastim
Drug: Topotecan Hydrochloride
Drug: Veliparib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Evaluation of ABT-888 (NCI Supplied Agent: ABT-888, NSC #737664), Topotecan (NSC # 609699) and Filgrastim or Pegfilgrastim in the Treatment of Persistent or Recurrent Squamous or Non-squamous Cell Carcinoma of the Cervix

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Duration of progression-free interval for all patients [ Time Frame: From study entry to time of progression or death, whichever comes first, assessed up to 5 years ] [ Designated as safety issue: No ]
  • Frequency and duration of objective response, by RECIST 1.1 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Frequency and severity of observed adverse events, graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
  • Number of patients with dose-limiting toxicities (in the safety lead-in), graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 21 days ] [ Designated as safety issue: Yes ]
  • Survival time for all patients [ Time Frame: From study entry to time of death or the date of last contact, assessed up to 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: February 2011
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (veliparib, topotecan hydrochloride, filgrastim)
Patients receive veliparib PO twice daily and topotecan hydrochloride IV over 30 minutes once daily on days 1-5. Patients also receive, according to institutional standard, filgrastim SC beginning on day 6, 7, or 8 and continuing until hematopoietic recovery or pegfilgrastim SC on day 6, 7, or 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Biological: Filgrastim
Given SC
Other Names:
  • FILGRASTIM
  • Filgrastim XM02
  • G-CSF
  • Neupogen
  • r-metHuG-CSF
  • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
  • rG-CSF
  • Tbo-filgrastim
  • Tevagrastim
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Pegfilgrastim
Given SC
Other Names:
  • Filgrastim SD-01
  • filgrastim-SD/01
  • Neulasta
  • PEGFILGRASTIM
  • SD-01
  • SD-01 sustained duration G-CSF
Drug: Topotecan Hydrochloride
Given IV
Other Names:
  • Hycamptamine
  • Hycamtin
  • SKF S-104864-A
  • Topotecan HCl
  • TOPOTECAN HYDROCHLORIDE
  • topotecan hydrochloride (oral)
Drug: Veliparib
Given PO
Other Names:
  • ABT-888
  • PARP-1 inhibitor ABT-888
  • VELIPARIB

Detailed Description:

PRIMARY OBJECTIVES:

I. To estimate the antitumor activity (objective response rate by RECIST 1.1) of ABT-888 (veliparib) 10 mg administered orally twice a day on days 1 to 5 with topotecan (topotecan hydrochloride) 0.6 mg/m^2 administered IV once daily on days 1 to 5 of each cycle in patients with persistent or recurrent carcinoma of the cervix.

II. To determine the nature and degree of toxicity of ABT-888 and topotecan in patients with persistent or recurrent carcinoma of the cervix.

SECONDARY OBJECTIVES:

I. To determine the duration of progression-free survival and overall survival.

TERTIARY OBJECTIVES:

I. To determine whether evidence of an interaction exists between study treatments and tumor expression of poly(ADP-ribos)ylation of E2 protein, E6/E7 proteins, and p53R2 in relation to progression-free and overall survival or metastasis. (Translational) II. To explore the association between methylation of FanCF and BRCA in pre-treatment tumor samples and pre- and post-treatment biopsy samples and response, progression-free and overall survival of patients, and/or metastasis. (Translational)

OUTLINE:

Patients receive veliparib orally (PO) twice daily and topotecan hydrochloride intravenously (IV) over 30 minutes once daily on days 1-5. Patients also receive, according to institutional standard, filgrastim subcutaneously (SC) beginning on day 6, 7, or 8 and continuing until hematopoietic recovery or pegfilgrastim SC on day 6, 7, or 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Tumor tissue samples may be collected periodically for translational studies.

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have persistent or recurrent squamous cell carcinoma, adenosquamous carcinoma, adenocarcinoma or non-squamous cell carcinoma of the cervix with documented disease progression; histological documentation of the original primary tumor is required via the pathology report
  • All patients must have measurable disease as defined by RECIST 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI
  • Patient must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
  • Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG Phase III protocol or Rare Tumor protocol for the same patient population
  • Patients must have a GOG performance status of 0, 1, or 2
  • Recovery from effects of recent surgery, radiotherapy, or chemotherapy
  • Patients should be free of active infection requiring antibiotics
  • Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration; continuation of hormone replacement therapy is permitted
  • Any other prior therapy directed at the malignant tumor, including chemotherapy, biologic/targeted (non-cytotoxic) therapy and immunologic agents must be discontinued at least three weeks prior to registration; all side effects must have resolved to =< grade 1 or stabilized, prior to enrolling on this study
  • Any prior radiation therapy must be completed at least 4 weeks prior to registration
  • Patients MUST have had one prior systemic chemotherapeutic regimen for management of advanced, metastatic, or recurrent squamous or non-squamous cell carcinoma of the cervix; chemotherapy administered concurrent with primary radiation is not counted as a systemic chemotherapy regimen (e.g.; weekly cisplatin); adjuvant chemotherapy given following the completion of radiation therapy (or concurrent chemotherapy and radiation therapy) is not counted as a systemic chemotherapy regimen (e.g.; paclitaxel and carboplatin for up to 4 cycles)
  • Patients who are registered during the safety lead-in portion of this protocol are required to have prior pelvic radiation
  • Patients must have NOT received more than one previous cytotoxic chemotherapy regimen (either with single or combination cytotoxic drug therapy)
  • Patients are allowed to receive, but are not required to receive, biologic/targeted (non-cytotoxic) therapy as part of their one prior systemic chemotherapeutic regimen; patients are allowed to receive, but are not required to receive, biologic/targeted (non-cytotoxic) therapy for management of recurrent or persistent disease
  • Patients MUST not be eligible for further curative intent surgical or pelvic radiation treatment for management of recurrent or persistent disease as determined by treating physicians
  • Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl
  • Platelets greater than or equal to 100,000/mcl
  • Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN)
  • Bilirubin less than or equal to 1.5 x ULN
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 x ULN
  • Alkaline phosphatase less than or equal to 2.5 x ULN
  • Neuropathy (sensory and motor) less than or equal to grade 1
  • Patients must have signed an approved informed consent and authorization permitting release of personal health information
  • Patients must meet pre-entry requirements
  • 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
  • Patients must have the ability to swallow pills whole

Exclusion Criteria:

  • Patients are excluded who have had prior therapy with ABT-888 (veliparib), poly (ADP)-ribose polymerase inhibitors, or topotecan
  • Patient with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
  • Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of cervical cancer within the last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
  • Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of cervical cancer within the last three years are excluded; patients may have received prior adjuvant chemotherapy for cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
  • Patients with seizures or history of seizures are ineligible
  • Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, any CNS metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study, are ineligible; patients with CNS metastases must be stable for > 3 months after treatment and off steroid treatment prior to study enrollment
  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: NCT01266447

  Show 78 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Charles Kunos NRG Oncology
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01266447     History of Changes
Other Study ID Numbers: NCI-2011-02659, NCI-2011-02659, CDR0000691281, GOG-0127W, GOG-0127W, U10CA180868, U10CA027469
Study First Received: December 23, 2010
Last Updated: August 5, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Carcinoma, Adenosquamous
Carcinoma, Small Cell
Carcinoma, Squamous Cell
Small Cell Lung Carcinoma
Uterine Cervical Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Genital Diseases, Female
Genital Neoplasms, Female
Lung Diseases
Lung Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Complex and Mixed
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Urogenital Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Uterine Neoplasms
Lenograstim
Topotecan
Adjuvants, Immunologic
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 31, 2015