Multicenter Trial With PegLiposomal Doxorubicin and Carboplatin Combination Chemotherapy in Gynecological Sarcomas and Mixed Epithelial-Mesenchymal Tumors

• ClinicalTrials.gov Identifier: NCT00815945
• Recruitment Status: Completed
• First Posted: December 31, 2008
• Last Update Posted: February 14, 2017
• Sponsor: AGO Study Group
• Collaborator: MSD SHARP & DOHME GmbH (formerly Essex Pharma GmbH)
• Information provided by (Responsible Party): AGO Study Group

Tracking Information

• First Submitted Date: December 30, 2008
• First Posted Date: December 31, 2008
• Last Update Posted Date: February 14, 2017
• Study Start Date: June 2008
• Actual Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 30, 2008): Anticancer activity in terms of progression-free survival time (PFS) [ Time Frame: every 3 months ]
• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT00815945 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: December 30, 2008)

• Tolerability, i.e. type, frequency, severity and duration of adverse reactions (CTCAE,Version 3.0) [ Time Frame: until recovery of toxicities ]
• Anticancer activity in patients with measurable or evaluable disease in terms of response rates (CR, PR, SD, PD) according to RECIST criteria [ Time Frame: six months ]
• Overall survival [ Time Frame: 30 months ]
• Correlation of tumor marker CA-125 with imaging methods [ Time Frame: six months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Multicenter Trial With PegLiposomal Doxorubicin and Carboplatin Combination Chemotherapy in Gynecological Sarcomas and Mixed Epithelial-Mesenchymal Tumors
• Official Title: Phase II Study Evaluating PegLiposomal Doxorubicin (PLD) and Carboplatin Combination Chemotherapy in Gynecological Sarcomas and Mixed Epithelial-Mesenchymal Tumors

Brief Summary

Uterine sarcomas account for less than 5% of all carcinomas of the uterine corpus. The prognosis of these patients is extremely limited. Recurrence rates of 50-60% are reported even for early-stage disease (FIGO I/II). Median overall survival is below 12 months in patients with advanced or metastatic disease.

Ovarian carcinosarcoma is extremely rare among ovarian malignancies (< 2%). That is why there is insufficient data as a basis for establishing a gold standard. As a result, these cases tend to be treated in the same way as uterine sarcomas or epithelial ovarian malignancies in clinical practice.

On the basis of data published to date on the treatment of mixed mesenchymal-epithelial tumors, it is clear that the treatments commonly used to date have limited activity while producing clinically relevant toxicity. The regimes verified so far (Cisplatin / Ifosfamide, Ifosfamide/Paclitaxel and Gemcitabine/Docetaxel) exhibit a considerable side effect spectrum and are only rarely feasible on clinical everyday life conditions, so e. g. the rate of withdrawals due to toxicity was in a study collective of selected females treated with the last combination at 40 %. The physician has to check in every individual case if one of the above mentioned combinations is feasible. The search for alternative effective and better tolerated treatment options is essential. The toxicity data on the carboplatin-PLD combination are known, and efficacy has been identified in small cohorts.

The objective of this study is to explore the efficacy of combination PLD-carboplatin treatment in a larger patient population.

Detailed Description

This study in patients with mesenchymal or mixed epithelial mesenchymal tumors of the ovary or uterus is designed as a prospective single-arm, open - label, multicenter phase II study to evaluate the efficacy of PegLiposomal Doxorubicin and Carboplatin combination chemotherapy.

40 patients will be recruited to receive PegLiposomal Doxorubicin (PLD) in a continuous i. v. infusion of at least 60 minutes at a dose of 40 mg/m2 on Day 1, followed by a 30-minute i. v. carboplatin infusion according to AUC 6 (formula devised by Calvert et al).

Patients will get outpatients treatment. At screening the patients' eligibility will be assessed, their baseline and demographic characteristics obtained, and baseline values for the effect variables collected. Patients with measurable lesions, non-measurable lesions or histological documentation will be included into this trial. Measurable lesion and non-measurable lesions will be documented by x-ray, ultrasound, computed tomography or MRI.

The patients' safety will be monitored during therapy until recovery of toxicities.

In patients with measurable lesions at baseline, the (post)-treatment values for effect according to the RECIST criteria will be collected as shown in table 6. CR, PR and SD have to be confirmed by a repeat measurement after an interval of at least four weeks.

Follow-up is scheduled every three months during the first two years after the end of treatment.

As from year 3 the follow-up takes place outside the study in the context of general aftercare.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Mesenchymal Tumor
• Carcinosarcoma
• Leiomyosarcoma

Intervention

• Drug: PegLiposomal Doxorubicin
  PegLiposomal Doxorubicin, intravenous, 40mg/m², every 28 days for up to 6 months
  Other Name: Caelyx
• Drug: Carboplatin
  Carboplatin, intravenous, AUC 6, every 28 days for up to 6 months

Study Arms

Experimental: PegLiposomal Doxorubicin + Carboplatin

Subjects will receive PegLiposomal Doxorubicin (40mg/m²) and Carboplatin (AUC6) every 28 days. Treatment period up to 6 months (therapy can be continued in case of tumor response and benefit for the patient)

Interventions:

• Drug: PegLiposomal Doxorubicin
• Drug: Carboplatin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 6, 2014): 41
• Original Estimated Enrollment (submitted: December 30, 2008): 40
• Actual Study Completion Date: January 2012
• Actual Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically documented mesenchymal or mixed epithelial-mesenchymal tumor of the ovary or uterus
• Patients with a primary diagnosis of FIGO I-IV uterine carcinosarcoma and optimum debulking (postoperative residual tumor < 1cm) may be enrolled only if cisplatin-ifosfamide combination therapy is not feasible.
• Patients with metastatic uterine carcinosarcoma may be enrolled only if Ifosfamide/Paclitaxel combination therapy is not feasible.
• Patients with metastatic leiomyosarcoma may be enrolled only if gemcitabine-docetaxel combination therapy is not feasible.
• Measurable (target lesion) tumor, evaluable (non-target lesion) tumor or histological documentation
• No more than one prior chemotherapy. Any prior platinum or anthracycline- containing chemotherapy must have been completed more than 6 months previously
• Prior radiotherapy ≤ 25% of the hematopoietic system is allowed provided it took place more than 6 weeks before recruitment
• Patients are allowed to have received prior anticancer hormone therapy or specific immunotherapy. Patients must have completed these therapies at least three weeks before recruitment to the study
• All women with a theoretical possibility of pregnancy must produce a negative pregnancy test (serum or urinary) within seven days before starting treatment
• General health of 0 - 2 on the ECOG score
• At least 18 years of age
• Estimated life expectancy above 12 weeks
• At least 3 weeks since major surgery
• Appropriate hematologic, renal and hepatic function in accordance with the following definitions:
• Absolute neutrophil count (ANC) ≥ 1.5 × 109 /l
• Platelets ≥ 100 × 10 9/l
• Total bilirubin ≤ 1.25 times upper limit of normal
• Estimated GFR ≥ 50 ml/min
• LVEF > 50 %
• Informed consent must be obtained from all patients.

Exclusion Criteria:

• More than one prior chemotherapy (or radiochemotherapy)
• Active infection or other serious medical impairment liable to affect the patient's ability to receive treatment according to protocol.
• Administration of other chemotherapy drugs or other anticancer hormone treatments during the study.
• History of clinically manifest atrial or ventricular arrhythmia (> LOWN II) and congestive heart failure, even if controlled by drugs (NYHA class > II). Documented myocardial infarction within 6 months before study enrollment.
• Pregnant or breastfeeding women, or women not practicing appropriate birth control methods
• Participation in another study using experimental drugs within the last 30 days
• Any other conditions or therapies which the physician believes might put the patient at risk or impair the study objective.
• Known hypersensitivity to carboplatin or pegylated liposomal doxorubicin

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: NCT00815945
• Other Study ID Numbers: AGO-GYN 7
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: AGO Study Group
• Study Sponsor: AGO Study Group
• Collaborators: MSD SHARP & DOHME GmbH (formerly Essex Pharma GmbH)

Investigators

• Principal Investigator: Philipp Harter, MD; Klinikum Essen Mitte

• PRS Account: AGO Study Group
• Verification Date: March 2014