Paclitaxel and Cisplatin or Topotecan With or Without Bevacizumab in Treating Patients With Stage IVB, Recurrent, or Persistent Cervical Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00803062
First received: December 4, 2008
Last updated: March 26, 2014
Last verified: March 2014

December 4, 2008
March 26, 2014
April 2009
March 2015   (final data collection date for primary outcome measure)
  • Overall survival [ Time Frame: From entry into the study to death or the date of last contact, assessed up to 5 years ] [ Designated as safety issue: No ]
  • Frequency and severity of adverse events assessed by NCI CTCAE version 3.0. [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]
    Defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease that occurs in a patient administered a medical treatment, whether the event is considered related or unrelated to the medical treatment
  • Overall survival [ Designated as safety issue: No ]
  • Frequency and severity of adverse events as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00803062 on ClinicalTrials.gov Archive Site
  • Progression-free survival [ Time Frame: From study entry until disease progression, death or date of last contact, assessed up to 5 years ] [ Designated as safety issue: No ]
  • Frequency of objective tumor response [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Health-related quality of life as assessed by FACT-Cx TOI; neuropathy symptoms as assessed by FACT/GOG-Ntx4 subscale; and pain as assessed by the Brief Pain Inventory at baseline, before courses 2 and 5, and at 6 and 9 months after course 1 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    95% confidence intervals will be reported for the estimated treatment differences of BPI score.
  • Progression-free survival [ Designated as safety issue: No ]
  • Frequency of objective tumor response [ Designated as safety issue: No ]
  • Health-related quality of life as assessed by FACT-Cx TOI; neuropathy symptoms as assessed by FACT/GOG-Ntx4 subscale; and pain as assessed by the Brief Pain Inventory at baseline, before courses 2 and 5, and at 6 and 9 months after course 1 [ Designated as safety issue: No ]
  • Impact of age, race, performance status, stage, histology, grade, disease site, prior chemoradiotherapy, and time to recurrence on response rate, progression-free survival, and overall survival [ Designated as safety issue: No ]
  • Prevalence of active smoking as assessed by the smoking questionnaire at baseline [ Designated as safety issue: No ]
  • Extent of nicotine dependence as assessed by the smoking questionnaire at baseline [ Designated as safety issue: No ]
  • Correlation of nicotine dependence with progression-free survival and overall survival [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Paclitaxel and Cisplatin or Topotecan With or Without Bevacizumab in Treating Patients With Stage IVB, Recurrent, or Persistent Cervical Cancer
A Randomized Phase III Trial of Cisplatin Plus Paclitaxel With and Without NCI-Supplied Bevacizumab (NSC #704865, IND #113912) Versus the Non-Platinum Doublet, Topotecan Plus Paclitaxel, With and Without NCI-Supplied Bevacizumab, In Stage IVB, Recurrent or Persistent Carcinoma of the Cervix

This randomized phase III trial is studying the side effects of paclitaxel when given together with cisplatin or topotecan with or without bevacizumab and to compare how well they work in treating patients with stage IVB, recurrent, or persistent cervical cancer. Drugs used in chemotherapy, such as paclitaxel, cisplatin, and topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether paclitaxel is more effective when given together with cisplatin or topotecan with or without bevacizumab in treating patients with cervical cancer.

PRIMARY OBJECTIVES:

I. To determine whether the addition of bevacizumab to chemotherapy improves overall survival. Also to determine if a regimen involving paclitaxel and topotecan improves overall survival in comparison to a regimen involving cisplatin and paclitaxel. These regimens are to be evaluated in patients with stage IVB, recurrent, or persistent carcinoma of the cervix.

II. To determine and compare the frequency and severity of adverse events as assessed by CTCAE version 3.0 for the regimens administered on this study.

SECONDARY OBJECTIVES:

I. To estimate and compare the progression-free survival of patients treated by the regimens investigated on this study.

II. To estimate and compare the proportion of patients with tumor responses by the regimens investigated on this study.

TERTIARY OBJECTIVES:

I. To determine whether the addition of bevacizumab to chemotherapy, or the substitution of cisplatin with topotecan improve the health related quality of life (QOL) as measured by the FACT-Cx TOI and produce favorable toxicity profiles (with a particular focus on peripheral neuropathy as measured by the FACT/GOG-Ntx4 subscale and pain as measured by BPI single item).

II. To evaluate the impact of age, race, performance status, stage, histology, grade, disease site, prior chemotherapy with primary radiation, and time to recurrence on response rate, progression-free survival and overall survival of patients with metastatic/recurrent/persistent carcinoma of the cervix.

III. To determine the prevalence of active smoking in this cohort of recurrent cervical cancer patients.

IV. To estimate the extent of tobacco/nicotine dependence in the cohort. V. To determine if smoking is an independent risk factor for progression-free survival and overall survival in this population.

VI. To isolate, enumerate and characterize circulating tumor cells (CTC) recovered from blood drawn pre-cycle 1, pre-cycle 2 and pre-cycle 3 using the CTC-chip developed by the Massachusetts General Hospital (MGH) BioMEMS Resource Center and the MGH Cancer Center.

VII. To determine the association between CTC counts or characteristics and measures of clinical outcome.

VIII. To examine the association between angiogenesis markers in plasma (recovered from blood drawn pre-cycle 1, pre-cycle 2 and pre-cycle 3) and measures of clinical outcome.

IX. To evaluate the association between tumor markers of angiogenesis and hypoxia (using archival formalin-fixed and paraffin-embedded tumor tissue) and measures of clinical outcome.

X. To evaluate the association between single nucleotide polymorphisms (using DNA extracted from whole blood) and measures of clinical outcome as well as measures of quality of life such as chemotherapy toxicity.

XI. To examine the relationship(s) among the various biomarkers. XII. To develop an optimal prognostic model for progression-free survival and overall survival using clinical covariates, smoking status and the various biomarkers.

OUTLINE: This is a multicenter study. Patients are stratified according to disease status (recurrent/persistent disease vs primary stage IVB disease), GOG performance status (0 vs 1), and prior platinum therapy as a radiosensitizer (yes vs no). Patients are randomized to 1 of 4 treatment arms.

ARM I: Patients receive paclitaxel IV over 3 hours or 24 hours on day 1 and cisplatin IV on day 1 or 2.

ARM II: Patients receive paclitaxel IV over 3 hours or 24 hours on day 1 and cisplatin IV and bevacizumab IV over 30-90 minutes on day 1 or 2.

ARM III: Patients receive paclitaxel IV over 3 hours on day 1 and topotecan hydrochloride IV over 30 minutes on days 1-3.

ARM IV: Patients receive paclitaxel IV over 3 hours and bevacizumab IV over 30-90 minutes on day 1 and topotecan hydrochloride IV over 30 minutes on days 1-3.

In all arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients complete quality-of-life questionnaires, including the FACT-Cx TOI, FACT/GOG-Ntx4, and Brief Pain Inventory, at baseline, before courses 2 and 5, and at 6 and 9 months after course 1. Patients also complete a smoking questionnaire at baseline. After completion of study therapy, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Cervical Adenocarcinoma
  • Cervical Adenosquamous Cell Carcinoma
  • Cervical Squamous Cell Carcinoma
  • Recurrent Cervical Cancer
  • Stage IVB Cervical Cancer
  • Drug: paclitaxel
    Given IV
    Other Names:
    • Anzatax
    • Asotax
    • TAX
    • Taxol
  • Drug: cisplatin
    Given IV
    Other Names:
    • CACP
    • CDDP
    • CPDD
    • DDP
  • Biological: bevacizumab
    Given IV
    Other Names:
    • anti-VEGF humanized monoclonal antibody
    • anti-VEGF monoclonal antibody
    • Avastin
    • rhuMAb VEGF
  • Drug: topotecan hydrochloride
    Given IV
    Other Names:
    • hycamptamine
    • Hycamtin
    • SKF S-104864-A
    • TOPO
  • Active Comparator: Arm I (paclitaxel and cisplatin)
    Patients receive paclitaxel IV over 3 hours or 24 hours on day 1 and cisplatin IV on day 1 or 2.
    Interventions:
    • Drug: paclitaxel
    • Drug: cisplatin
  • Experimental: Arm II (paclitaxel, cisplatin, bevacizumab)
    Patients receive paclitaxel IV over 3 hours or 24 hours on day 1 and cisplatin IV and bevacizumab IV over 30-90 minutes on day 1 or 2.
    Interventions:
    • Drug: paclitaxel
    • Drug: cisplatin
    • Biological: bevacizumab
  • Experimental: Arm III (topotecan hydrochloride and paclitaxel)
    Patients receive paclitaxel IV over 3 hours on day 1 and topotecan hydrochloride IV over 30 minutes on days 1-3.
    Interventions:
    • Drug: paclitaxel
    • Drug: topotecan hydrochloride
  • Experimental: Arm IV (topotecan hydrochloride, paclitaxel, bevacizumab)
    Patients receive paclitaxel IV over 3 hours and bevacizumab IV over 30-90 minutes on day 1 and topotecan hydrochloride IV over 30 minutes on days 1-3.
    Interventions:
    • Drug: paclitaxel
    • Biological: bevacizumab
    • Drug: topotecan hydrochloride
Tewari KS, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014 Feb 20;370(8):734-43. doi: 10.1056/NEJMoa1309748.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
450
Not Provided
March 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically confirmed carcinoma of the cervix, including any of the following subtypes:

    • Squamous cell carcinoma
    • Adenosquamous cell carcinoma
    • Adenocarcinoma
  • Primary stage IVB, recurrent, or persistent disease not amenable to curative treatment with surgery and/or radiotherapy
  • Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan

    • Biopsy confirmation required if target lesion(s) measures < 30 mm or if the treating physician determines it is clinically indicated
    • Has ≥ 1 "target lesion" that can be used to assess response

      • Tumors within a previously irradiated field are designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence ≥ 90 days following completion of radiotherapy
  • No history or evidence of CNS disease, including primary brain tumor, brain metastases, or craniospinal metastases
  • GOG performance status 0-1
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Bilirubin ≤ 1.5 times normal
  • SGOT ≤ 2.5 times normal
  • Alkaline phosphatase ≤ 2.5 times normal
  • PT/INR ≤ 1.5 (or in-range INR, if patient is on a stable dose of therapeutic warfarin for management of venous thrombosis, including pulmonary thromboembolus)
  • PTT < 1.2 times upper limit of normal
  • Serum creatinine normal OR creatinine clearance ≥ 60 mL/min
  • Urine protein:creatinine ratio 1.0 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
  • No active infection requiring antibiotics
  • No significant traumatic injury within the past 28 days
  • No serious non-healing wound, ulcer, or bone fracture

    • Patients with granulating incisions healing by secondary intention are eligible provided there is no evidence of fascial dehiscence or infection AND the wound is examined weekly
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 3-6 months

    • Patients must have undergone correction (or spontaneous healing) of the perforation/fistula and/or the underlying process causing the fistula/perforation
  • No clinical symptoms or signs of gastrointestinal obstruction requiring parenteral hydration and/or nutrition
  • No active bleeding or pathologic condition that carries a high risk of bleeding (e.g., known bleeding disorder, coagulopathy, or tumor involving major vessels)
  • No seizures not controlled with standard medical therapy
  • No cerebrovascular accident (i.e., stroke), transient ischemic attack, or subarachnoid hemorrhage within the past 6 months
  • No clinically significant cardiovascular disease, including any of the following:

    • Uncontrolled hypertension, defined as systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg
    • Myocardial infarction or unstable angina within the past 6 months
    • NYHA class II-IV congestive heart failure
    • Serious cardiac arrhythmia requiring medication

      • Atrial fibrillation allowed provided it is asymptomatic and ventricular rate is controlled
    • Significant peripheral vascular disease (i.e., ≥ grade 2 peripheral vascular disease, as defined by NCI CTCAE v3.0 criteria)
  • No bilateral hydronephrosis that cannot be alleviated by ureteral stents or percutaneous drainage
  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
  • No other invasive malignancy within the past 5 years, except nonmelanoma skin cancer
  • No other medical history or condition that, in the opinion of the investigator, would preclude study participation
  • No peripheral neuropathy ≥ grade 2
  • Recovered from all prior therapy
  • No prior anti-cancer therapy that would preclude study therapy
  • No prior anti-VEGF drugs, including bevacizumab
  • No prior chemotherapy unless given concurrently with radiotherapy

    • Prior paclitaxel and/or topotecan with radiotherapy not allowed
  • At least 6 weeks since prior chemoradiotherapy
  • At least 3 weeks since prior radiotherapy alone
  • More than 28 days since prior major surgery or open biopsy
  • More than 7 days since prior core biopsy
  • No concurrent major surgery including, but not limited to, abdominal surgery prior to disease progression (e.g., colostomy or enterostomy reversal, interval or secondary cytoreductive surgery, or second-look surgery via laparotomy or laparoscopy)
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Spain
 
NCT00803062
NCI-2009-01084, NCI-2009-01084, CDR0000628746, GOG-0240, GOG-0240, GOG-0240, U10CA027469
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Krishnansu Tewari Gynecologic Oncology Group
National Cancer Institute (NCI)
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP