Paclitaxel, Cisplatin, and Veliparib in Treating Patients With Advanced, Persistent, or Recurrent Cervical Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01281852
First received: January 21, 2011
Last updated: September 30, 2014
Last verified: June 2014
  Purpose

This phase I/II clinical trial is studying the side effects and the best dose of veliparib when given with paclitaxel and cisplatin and to see how well they work in treating patients with advanced, persistent, or recurrent cervical cancer. Drugs used in chemotherapy, such as paclitaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving more than one drug (combination chemotherapy) and giving chemotherapy together with veliparib may kill more tumor cells.


Condition Intervention Phase
Cervical Adenocarcinoma
Cervical Adenosquamous Cell Carcinoma
Cervical Squamous Cell Carcinoma
Recurrent Cervical Cancer
Stage IVB Cervical Cancer
Drug: veliparib
Other: immunohistochemistry staining method
Other: diagnostic laboratory biomarker analysis
Drug: cisplatin
Drug: paclitaxel
Phase 1
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 Limited Access Phase I/II Trial of Paclitaxel, Cisplatin and CTEP Supplied Agent ABT-888 (Veliparib) (NSC#737664) in the Treatment of Advanced, Persistent, or Recurrent Carcinoma of the Cervix

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Dose-limiting toxicities in the first course of treatment (phase I) [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
  • Frequency and severity of adverse effects as assessed by NCI CTCAE v. 4.0 [ Time Frame: Up to 30 days of last protocol treatment ] [ Designated as safety issue: Yes ]
  • Objective tumor response (complete or partial response) (phase II) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival (phase II) [ Time Frame: From study entry to time of progression or death, whichever occurs first, assessed up to 5 years ] [ Designated as safety issue: No ]
  • Overall survival (phase II) [ 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: 66
Study Start Date: April 2011
Estimated Primary Completion Date: March 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (paclitaxel, cisplatin, veliparib)
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.
Drug: veliparib
Given orally
Other Name: ABT-888
Other: immunohistochemistry staining method
Correlative studies
Other Name: immunohistochemistry
Other: diagnostic laboratory biomarker analysis
Correlative studies
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol

Detailed Description:

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.

  Eligibility

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

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
  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: NCT01281852

  Show 26 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Ritu Salani Gynecologic Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01281852     History of Changes
Other Study ID Numbers: NCI-2011-02661, NCI-2011-02661, GOG-0076HH, CDR0000693745, GOG-0076HH, GOG-0076HH, U10CA027469
Study First Received: January 21, 2011
Last Updated: September 30, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Adenocarcinoma
Uterine Cervical Neoplasms
Carcinoma
Carcinoma, Adenosquamous
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Neoplasms, Complex and Mixed
Paclitaxel
Cisplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on October 01, 2014