Study on Paclitaxel Plus Topotecan in Comparison With Topotecan Plus Cisplatin in Recurrent or Persistent Cervical Carcinoma (AGO-Zervix-1)

• ClinicalTrials.gov Identifier: NCT01405235
• Recruitment Status: Unknown
• First Posted: July 29, 2011
• Last Update Posted: April 12, 2012
• Sponsor: Institut fuer Frauengesundheit
• Collaborators: GlaxoSmithKline; Schantl Pharma Service, Germany
• Information provided by: Institut fuer Frauengesundheit

Tracking Information

• First Submitted Date: July 27, 2011
• First Posted Date: July 29, 2011
• Last Update Posted Date: April 12, 2012
• Study Start Date: September 2006
• Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 28, 2011): Changes in target lesion according to RECIST 1.0 [ Time Frame: week 12 ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study on Paclitaxel Plus Topotecan in Comparison With Topotecan Plus Cisplatin in Recurrent or Persistent Cervical Carcinoma
• Official Title: A Prospective, Randomized Phase III Study to Compare the Effects of Paclitaxel and Topotecan to Those of Cisplatin and Topotecan for Treatment of Patients With Recurrent and Persistent Cervical Cancer
• Brief Summary: Current planning for studies involving patients with recurrent, persistent, or metastasized cervical cancer must take into consideration that up to 75% of all patients are assumed to have already been treated with cisplatin in conjunction with radiation therapy. It seems questionable to continue to treat patients with cisplatin when cancer has recurred. Thus, it is important to seek alternative active combinations. The studies GOG 169 and 179 demonstrated that a combination of paclitaxel and cisplatin was superior to a cisplatin monotherapy with respect to therapeutic response and progression-free survival, as was a combination of topotecan and cisplatin with respect to therapeutic response, progression-free survival, and total survival. To achieve further improvement in total survival and to answer questions regarding the value of using a platinum-free combination, we propose that a study should be conducted to compare the efficacy of a platinum-free combination of paclitaxel and topotecan to a combination of cisplatin and topotecan.

Detailed Description

Design: This will be a prospective, randomized, multicenter, non-blinded phase III A study.

Dosages: Arm A Paclitaxel 70 mg/m2/d i.v. on Days 1, 8, and 15 in combination with Topotecan 1.75 mg/m2/d i.v. on Days 1, 8, and 15, q 28 d Arm B Topotecan 0.75 mg/m2/d i.v. on Days 1- 3 in combination with Cisplatin 50 mg/m2 i.v. on Day 1, q 21 d Duration of Therapy: Each patient will participate in the study until a maximum of six cycles have been completed, or until there is evidence of disease progression, or until toxicity prevents further therapy. Patients with continued response or stable disease may continue to participate in the study for an additional 3 cycles beyond the original 6 cycles with consent of the Study Director, but this must be documented in the CRF.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Recurrent, Persistent or Metastasized Cervical Cancer

Intervention

• Drug: Paclitaxel
  Paclitaxel 70 mg/m2/d i.v. on Days 1, 8, and 15 in combination with Topotecan 1.75 mg/m2/d i.v. on Days 1, 8, and 15, q 28 d
• Drug: Cisplatin/Paclitaxel
  Topotecan 0.75 mg/m2/d i.v. on Days 1- 3 in combination with Cisplatin 50 mg/m2 i.v. on Day 1, q 21 d

Study Arms

• Active Comparator: Arm B: Cisplatin/Topotecane
  Topotecan 0.75 mg/m2/d i.v. on Days 1- 3 in combination with Cisplatin 50 mg/m2 i.v. on Day 1, q 21 d
  Intervention: Drug: Cisplatin/Paclitaxel
• Experimental: Arm A: Paclitaxel/Topotecan
  Paclitaxel 70 mg/m2/d i.v. on Days 1, 8, and 15 in combination with Topotecan 1.75 mg/m2/d i.v. on Days 1, 8, and 15, q 28 d
  Intervention: Drug: Paclitaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: July 28, 2011): 312
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 2015
• Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients must have a histologically confirmed recurrent, persistent, or metastasized squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix, for which a curative treatment by operation and/or radiation therapy is not possible.
• Patients must have been previously treated with cisplatin in the context of radiochemotherapy.
• All patients must present with measurable disease. Measurable disease is defined as a minimum of one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must measure ≥ 20 mm when measured by conventional techniques, including palpation, x-ray, CT, and MRI, or ≥ 10 mm when measured by spiral CT. Patients must have at least one "target lesion" that can be used to evaluate response according to RECIST criteria during this study.
• When a biopsy is performed, it should be performed on this lesion. A lesion outside of the irradiated area should ideally be selected as the "target lesion" on patients who have tumors both inside and outside a previously irradiated area. A previously irradiated lesion may only be considered as a "target lesion" if, after the radiation therapy had been completed, this lesion objectively led to a diagnosis of recurrence, or progress specific to this lesion was observed.

• Patients must display the following:

  • Sufficient hematologic function: absolute neutrophil count ≥ 1.
  • 500/μl; granulocytes > 3,000/μl; thrombocytes ≥ 100,000/μl.
  • Sufficient renal function: serum creatinine ≤ 1.2 mg/dl. In patients with a serum A prospective, randomized phase III study to compare the effects of Paclitaxel and Topotecan to those of Cisplatin and Topotecan for treatment of patients with recurrent or persistent cervical cancer Page 24 Study Protocol Version 1.1 dated 09/25/2006 creatinine of > 1.2 mg/dl, the results of a 24-hour creatinine clearance must yield a level > 50 cm3/min for eligibility.
  • Sufficient liver function: bilirubin ≤ 1.5 times the institutional upper limit of normal, GOT, alkaline phosphatase ≤ 3 times the institutional upper limit of normal.
  • Patients must display an ECOG performance status of 0-2 (Karnofsky > 60%).
  • Patients must have recovered from the aftereffects of any surgery, radiation therapy, or chemotherapy. A minimum of six weeks must have passed since the last administration of chemotherapy, and at least three weeks must have passed since the last treatment with radiation alone.
  • Patients must have signed an official consent document which also authorizes the release of personal health information. Patients unable to give their consent independently may not participate in the study.
  • Patients must fulfill all the requirements defined in Section 8.1, including completion of a baseline quality of life questionnaire, prior to their inclusion in the study.
  • Patients must be free of clinically significant infection.
  • Patients must be 18 years of age or older.

Exclusion Criteria:

• Patients with bilateral hydronephrosis which cannot be alleviated by ureteral stents or percutaneous drainage. Patients with a serum creatinine > 1.2 mg/dl but < 1.5 mg/dl and a 24-hour creatinine clearance result of < 50 cm3/min. Patients with a serum creatinine ≥ 1.5 mg/dl. A prospective, randomized phase III study to compare the effects of Paclitaxel and Topotecan to those of Cisplatin and Topotecan for treatment of patients with recurrent or persistent cervical cancer Study Protocol Version 1.1 dated 09/25/2006 Page 25

  • Patients who have received prior chemotherapy, unless the chemotherapy was administered with concomitant radiation therapy.
  • Patients who are pregnant or lactating.
  • Patients with craniospinal metastases.
  • Patients with a concomitant malignant disease, with the exception of nonmelanoma skin cancer.
  • Patients with a previous invasive malignant disease (other than nonmelanoma skin cancer) showing evidence of this disease within the last 5 years, or for whom the therapy to be administered during this study is contraindicated due to previous treatment received for this malignant disease.
  • Patients who are participating in another clinical study at the same time or who will have done so up to 30 days before the planned end of this study.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT01405235
• Other Study ID Numbers: IFG-01-0106
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Frau Dr. med. Patricia Oppelt, Institut fuer Frauengesundheit GmbH
• Original Responsible Party: Same as current
• Current Study Sponsor: Institut fuer Frauengesundheit
• Original Study Sponsor: Same as current

Collaborators

• GlaxoSmithKline
• Schantl Pharma Service, Germany

Investigators

• Study Chair: Falk Thiel, Dr. med.; Frauenklinik Universitätsklinikum Erlangen

• PRS Account: Institut fuer Frauengesundheit
• Verification Date: September 2006