Study on Paclitaxel Plus Topotecan in Comparison With Topotecan Plus Cisplatin in Recurrent or Persistent Cervical Carcinoma

NCT ID: NCT01405235

Last Updated: 2012-04-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 312 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2015-01-31

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.

Conditions

Recurrent, Persistent or Metastasized Cervical Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Cisplatin/Paclitaxel

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Paclitaxel

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Schantl Pharma Service, Germany

UNKNOWN

Sponsor Role: collaborator

Institut fuer Frauengesundheit

OTHER

Sponsor Role: lead

Responsible Party

Institut fuer Frauengesundheit GmbH

Principal Investigators

Falk Thiel, Dr. med.

Role: STUDY_CHAIR

Frauenklinik Universitätsklinikum Erlangen

Locations

Universitätsfrauenklinik

Erlangen, Bavaria, Germany

Countries

Germany

References

Gass P, Thiel FC, Haberle L, Ackermann S, Theuser AK, Hummel N, Boehm S, Kimmig R, Reinthaller A, Becker S, Hilpert F, Janni W, Vergote I, Harter P, Emons J, Hein A, Beckmann MW, Fasching PA, Poschke P; AGO Uterus Commission. Primary results of the AGO-Zervix-1 Study: A prospective, randomized phase III study to compare the effects of paclitaxel and topotecan with those of cisplatin and topotecan in the treatment of patients with recurrent and persistent cervical cancer. Gynecol Oncol. 2024 Apr;183:25-32. doi: 10.1016/j.ygyno.2024.03.002. Epub 2024 Mar 14.

Reference Type: DERIVED

PMID: 38490057 (View on PubMed)

Other Identifiers

IFG-01-0106

Identifier Type: -

Identifier Source: org_study_id