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A Limited Access Phase I/II Trial of Paclitaxel, Cisplatin and CTEP Supplied Agent ABT-888 (Veliparib) (IND#77840, NSC#737664) in the Treatment of Advanced, Persistent, or Recurrent Carcinoma of the Cervix


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Female
Cervical Adenocarcinoma, Cervical Adenosquamous Cell Carcinoma, Cervical Squamous Cell Carcinoma, Recurrent Cervical Cancer, Stage IVB Cervical Cancer

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Trial Information

A Limited Access Phase I/II Trial of Paclitaxel, Cisplatin and CTEP Supplied Agent ABT-888 (Veliparib) (IND#77840, NSC#737664) in the Treatment of Advanced, Persistent, or Recurrent Carcinoma of the Cervix


PRIMARY OBJECTIVES:

I. To determine the maximum-tolerated dose (MTD) and dose-limiting toxicities of veliparib
when combined with cisplatin and paclitaxel in women with advanced, persistent, or recurrent
cervical cancer.

II. To examine the safety of veliparib when combined with cisplatin and paclitaxel.

III. To estimate the efficacy of cisplatin, paclitaxel, and veliparib (with respect to
objective tumor response) in patients with advanced, persistent, or recurrent carcinoma of
the cervix once the recommended phase II dose is established.

SECONDARY OBJECTIVES:

I. To examine the effects of this regimen on progression-free survival and overall survival.

II. To determine the proportion of patients with advanced, persistent, or recurrent cancer
of the cervix whose tumors demonstrate loss of the FancD2 foci formation. (Exploratory) III.
To determine the association between loss of FancD2 foci formation and progression-free
survival, overall survival, and response in this patient population. (Exploratory)

OUTLINE: This is a multicenter, phase I, dose-escalation study of veliparib followed by a
phase II study. Patients in phase II are stratified according to prior cisplatin as a
radiation sensitizer (yes vs no).

Patients receive paclitaxel IV over 3 hours on day 1, cisplatin IV over 1 hour on day 2, and
veliparib orally on days 1-7. Courses repeat every 21 days in the absence of disease
progression or unacceptable toxicity. Tumor tissue samples may be collected for FancD2 foci
formation analysis by IHC.

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


Inclusion Criteria:



- Patients must have primary stage IVB, recurrent, or persistent squamous cell
carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix that is not
amenable to curative treatment with surgery and/or radiotherapy

- Histologic documentation of the original primary tumor is required via the
pathology report

- All patients in the phase I portion must have received prior chemoradiation

- Measurable disease not required for patients in the phase I portion

- All patients in the phase II portion 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 dimension to be recorded)

- Each lesion must be ≥ 10 mm when measured by CT scan, 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 scan or MRI

- Patients in the phase II portion 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 radiotherapy

- No patients with history or evidence, upon physical examination, of CNS disease,
including primary brain tumor or brain metastases, within the past 6 months of the
first date of treatment on this study

- GOG performance status 0-2

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 9 g/dL

- Creatinine normal OR creatinine clearance ≥ 60 mL/min

- Calcium, magnesium, phosphate, and potassium normal

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST and ALT ≤ 3 times ULN

- Alkaline phosphatase ≤ 2.5 times ULN

- Not pregnant or nursing

- Negative pregnancy test

- Women of child-bearing potential must agree to use adequate contraception (hormonal,
barrier method of birth control, or abstinence) prior to study entry and for the
duration of study participation

- Able to swallow medication

- Free of active infection requiring antibiotics (with the exception of uncomplicated
urinary tract infection [UTI])

- Peripheral neuropathy (sensory and motor) ≤ grade 1

- No history of other invasive malignancies, with the exception of non-melanoma skin
cancer and other specific malignancies, within the past 3 years.

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to veliparib or other agents used in study

- No 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

- No history of cerebrovascular accident (CVA, stroke), transient ischemic attack
(TIA), or subarachnoid hemorrhage within the past 6 months of the first date of
treatment on this study

- No other concurrent investigational agents

- Recovered from effects of recent surgery, radiotherapy, or other therapy

- At least 1 week since prior hormonal therapy directed at the malignant tumor

- Continuation of hormone replacement therapy is permitted

- At least 6 weeks since prior chemoradiotherapy

- At least 3 weeks since prior radiotherapy alone

- At least 6 weeks since prior major surgery

- No prior cancer treatment that contraindicates this protocol therapy

- No prior veliparib or other PARP inhibitors

- No prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for
the treatment of cervical cancer within the last 3 years

- Prior radiotherapy for localized cancer of the breast, head and neck, or skin is
permitted, provided that it was completed more than 3 years prior to
registration and the patient remains free of recurrent or metastatic disease

- No prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment
of cervical cancer within the last 3 years

- Prior adjuvant chemotherapy for localized breast cancer allowed, provided that
it was completed more than 3 years prior to registration and the patient remains
free of recurrent or metastatic disease

- No prior chemotherapy for cervical cancer except when used concurrently with
radiotherapy

- No patients who have received concurrent paclitaxel with radiation therapy

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Dose-limiting toxicities in the first course of treatment (phase I)

Outcome Time Frame:

21 days

Safety Issue:

Yes

Principal Investigator

Ritu Salani

Investigator Role:

Principal Investigator

Investigator Affiliation:

Gynecologic Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-02661

NCT ID:

NCT01281852

Start Date:

April 2011

Completion Date:

Related Keywords:

  • Cervical Adenocarcinoma
  • Cervical Adenosquamous Cell Carcinoma
  • Cervical Squamous Cell Carcinoma
  • Recurrent Cervical Cancer
  • Stage IVB Cervical Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Uterine Cervical Neoplasms
  • Carcinoma, Adenosquamous

Name

Location

Johns Hopkins UniversityBaltimore, Maryland  21205
Memorial Sloan Kettering Cancer CenterNew York, New York  10021
Cleveland Clinic FoundationCleveland, Ohio  44195
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Washington University School of MedicineSaint Louis, Missouri  63110
University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73104
MetroHealth Medical CenterCleveland, Ohio  44109
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical CenterColumbus, Ohio  43210-1240
Singing River HospitalPascagoula, Mississippi  39581
University of VirginiaCharlottesville, Virginia  22908
Case Western Reserve UniversityCleveland, Ohio  44106
Riverside Methodist HospitalColumbus, Ohio  43214
University of Texas Southwestern Medical CenterDallas, Texas  
Virginia Commonwealth UniversityRichmond, Virginia  
Hillcrest Hospital Cancer CenterMayfield Heights, Ohio  44124
Cancer Care Associates-YaleTulsa, Oklahoma  74136-1929
Women and Infants HospitalProvidence, Rhode Island  02905
Georgia Health Sciences UniversityAugusta, Georgia  30912
Gynecologic Oncology GroupPhiladelphia, Pennsylvania  19103