Clinical Trials

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

Location:

Jacksonville,  FL,  Rochester,  MN

Trial status:

Open for Enrollment

Why is this study being done?

OBJECTIVES:

Primary

- To compare the overall survival of patients with stage IVB, recurrent, or persistent carcinoma of the cervix treated with paclitaxel in combination with cisplatin or topotecan with vs without bevacizumab.

- To compare the frequency and severity of adverse events associated with these regimens as assessed by NCI CTCAE v3.0.

Secondary

- To compare the progression-free survival of these patients.

- To compare the proportion of patients with tumor response.

Tertiary

- To compare the health-related quality of life as assessed by the FACT-Cx TOI; neuropathy symptoms as assessed by the FACT/GOG-Ntx4 subscale; and pain as assessed by the Brief Pain Inventory in these patients.

- To evaluate the 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 of these patients.

- To determine the prevalence of active smoking in these patients.

- To estimate the extent of tobacco/nicotine dependence in these patients.

- To determine if smoking is an independent risk factor for progression-free survival and overall survival of these patients.

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.

Who is eligible to participate?

DISEASE CHARACTERISTICS:

- 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

PATIENT CHARACTERISTICS:

- 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

PRIOR CONCURRENT THERAPY:

- 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)

Last updated: 03/26/2012

NCT ID:

NCT00803062