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A Phase II Evaluation of ABT-888 (IND# 77840, 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


Phase 2
18 Years
N/A
Not Enrolling
Female
Cervical Adenocarcinoma, Cervical Adenosquamous Cell Carcinoma, Cervical Small Cell Carcinoma, Cervical Squamous Cell Carcinoma, Recurrent Cervical Cancer, Stage III Cervical Cancer, Stage IVA Cervical Cancer, Stage IVB Cervical Cancer

Thank you

Trial Information

A Phase II Evaluation of ABT-888 (IND# 77840, 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


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.


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 CT, 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 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 had one prior systemic chemotherapeutic regimen for management of
advanced, metastatic, or recurrent squamous cell or non-squamous cell carcinoma of
the cervix

- Chemotherapy administered in conjunction with primary radiation as a radiation
sensitizer is not counted as a systemic chemotherapy regimen

- Patients are required to have prior pelvic radiation (for patients who are registered
during the safety lead-in portion of this protocol)

- 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

- Patients must have a GOG performance status of 0, 1, or 2

- 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 of normal (ULN)

- Bilirubin less than or equal to 1.5 x ULN

- SGOT (AST) less than or equal to 3 x ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use adequate contraception (hormonal or barrier method of birth
control; abstinence) prior to study entry and for the duration of study participation

- Patients must have the ability to swallow pills whole

- Patients should be free of active infection requiring antibiotics

- Neuropathy (sensory and motor) less than or equal to grade 1

- Patients with 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 excluded

- Patients may NOT receive amifostine or other protective agents

- Patients must have NOT received more than one previous cytotoxic chemotherapy regimen
(either with single or combination cytotoxic drug therapy)

- Patients are allowed to have received, but are not required to have received, one
additional non-cytotoxic regimen for management of recurrent or persistent disease
according to the following definition:

- Non-cytotoxic (biologic or cytostatic) agents include (but are not limited to)
monoclonal antibodies, cytokines, and small-molecule inhibitors of signal
transduction

- Recovered from effects of recent surgery, radiotherapy, or chemotherapy

- 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 biological 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

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 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
excluded; patients with CNS metastases must be stable for > 3 months after
treatment and off steroid treatment prior to study enrollment

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Frequency and duration of objective response, by RECIST 1.1

Outcome Time Frame:

Up to 5 years

Safety Issue:

No

Principal Investigator

Charles Kunos

Investigator Role:

Principal Investigator

Investigator Affiliation:

Gynecologic Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-02659

NCT ID:

NCT01266447

Start Date:

February 2011

Completion Date:

Related Keywords:

  • Cervical Adenocarcinoma
  • Cervical Adenosquamous Cell Carcinoma
  • Cervical Small Cell Carcinoma
  • Cervical Squamous Cell Carcinoma
  • Recurrent Cervical Cancer
  • Stage III Cervical Cancer
  • Stage IVA Cervical Cancer
  • Stage IVB Cervical Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Uterine Cervical Neoplasms
  • Small Cell Lung Carcinoma
  • Carcinoma, Small Cell
  • Carcinoma, Adenosquamous

Name

Location

Johns Hopkins UniversityBaltimore, Maryland  21205
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Abington Memorial HospitalAbington, Pennsylvania  19001
Fox Chase Cancer CenterPhiladelphia, Pennsylvania  19111
University of Washington Medical CenterSeattle, Washington  98195-6043
Tacoma General HospitalTacoma, Washington  98405
Hurley Medical CenterFlint, Michigan  48503
Bronson Methodist HospitalKalamazoo, Michigan  49007
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Borgess Medical CenterKalamazooaa, Michigan  49001
Waukesha Memorial HospitalWaukesha, Wisconsin  53188
North Shore University HospitalManhasset, New York  11030
University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73104
Scott and White Memorial HospitalTemple, Texas  76508
Group Health CooperativeSeattle, Washington  98112
Long Island Jewish Medical CenterNew Hyde Park, New York  11040
Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109
Cancer Care Northwest - Spokane SouthSpokane, Washington  99202
University of New Mexico Cancer CenterAlbuquerque, New Mexico  87131-5636
Parkland Memorial HospitalDallas, Texas  75235
Saint Joseph Mercy HospitalAnn Arbor, Michigan  48106
Wenatchee Valley Medical CenterWenatchee, Washington  98801-2028
Seattle Cancer Care AllianceSeattle, Washington  98109
Genesys Regional Medical CenterGrand Blanc, Michigan  48439-8066
Pacific Gynecology SpecialistsSeattle, Washington  98104
Memorial Medical CenterSpringfield, Illinois  62781
Saint Alphonsus Regional Medical CenterBoise, Idaho  83706
Case Western Reserve UniversityCleveland, Ohio  44106
Riverside Methodist HospitalColumbus, Ohio  43214
Indiana University Medical CenterIndianapolis, Indiana  46202
University of Texas Southwestern Medical CenterDallas, Texas  
Northwest HospitalSeattle, Washington  98133
Decatur Memorial HospitalDecatur, Illinois  62526
Virginia Commonwealth UniversityRichmond, Virginia  
Florida HospitalOrlando, Florida  32803
Memorial Health University Medical CenterSavannah, Georgia  31404
Harrison Medical CenterBremerton, Washington  98310
Saint Francis Hospital and Medical CenterHartford, Connecticut  06105
The Hospital of Central ConnecticutNew Britain, Connecticut  06050
Michigan Cancer Research Consortium Community Clinical Oncology ProgramAnn Arbor, Michigan  48106
Oakwood HospitalDearborn, Michigan  48123
Saint John Hospital and Medical CenterDetroit, Michigan  48236
Allegiance HealthJackson, Michigan  49201
Sparrow HospitalLansing, Michigan  48912
Saint Mary Mercy HospitalLivonia, Michigan  48154
Saint Joseph Mercy OaklandPontiac, Michigan  48341-2985
Saint Joseph Mercy Port HuronPort Huron, Michigan  48060
Saint Mary's of MichiganSaginaw, Michigan  48601
Ozark Health Ventures LLC dba Cancer Research for The Ozarks SpringfieldSpringfield, Missouri  65802
Saint John's HospitalSpringfield, Missouri  65804
Cox Medical CenterSpringfield, Missouri  65807
Cooper Hospital University Medical CenterCamden, New Jersey  08103
Harrison Bremerton Hematology and OncologyBremerton, Washington  98310
Swedish Medical Center-First HillSeattle, Washington  98122-4307
Saint Joseph Medical CenterTacoma, Washington  98405
Oconomowoc Memorial Hospital-ProHealth Care IncOconomowoc, Wisconsin  53066-3896
University of California Medical Center At Irvine-Orange CampusOrange, California  92868
Cancer Care Associates-YaleTulsa, Oklahoma  74136-1929
Women and Infants HospitalProvidence, Rhode Island  02905
Lake University Ireland Cancer CenterMentor, Ohio  44060
University of Colorado Cancer Center - Anschutz Cancer PavilionAurora, Colorado  80045
State University of New York Downstate Medical CenterBrooklyn, New York  11203
Monter Cancer CenterLake Success, New York  11042
Southwest Gynecologic Oncology Associates IncAlbuquerque, New Mexico  87106
Women's Cancer Center of NevadaLas Vegas, Nevada  89109
Providence Regional Cancer PartnershipEverett, Washington  98201
Sudarshan K Sharma MD Limted-Gynecologic OncologyHinsdale, Illinois  60521
University Medical Center BrackenridgeAustin, Texas  78701
PeaceHealth Medical Group PCBellingham, Washington  98226
Skagit Valley Hospital Regional Cancer Care CenterMount Vernon, Washington  98274
Olympic Medical Cancer Care CenterSequim, Washington  98384
Rockwood Cancer Treatment CenterSpokane, Washington  99204
Providence Saint Mary Regional Cancer CenterWalla Walla, Washington  99362
Harrison Poulsbo Hematology and OncologyPoulsbo, Washington  98370
D N Greenwald CenterMukwonago, Wisconsin  53149