| General information |
| Database: | DB00531 |
| Objective: | The mTOR inhibitor, temsirolimus, has clinical activity in the treatment of gynecologic malignancies, particularly endometrial cancer. they sought to determine the tolerability of the combination of weekly topotecan with weekly temsirolimus. |
| Authors: | Temkin SM, et al |
| Title: | a phase I study of weekly temsirolimus and topotecan in the treatment of advanced and/or recurrent gynecologic malignancies. |
| Journal: | Gynecol Oncol. |
| Year: | 2010 |
| PMID: | 20347480 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | temsirolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | vulvar carcinoma,vaginal carcinoma, ovarian, primary peritoneal, or fallopian tube carcinoma,endometrial carcinoma,cervical cancer |
| Cancer Subtype: | gynecologic malignancies |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | weekly temsirolimus and topotecan |
| Study Type: | phase I study |
| Key Patients Feature: | Patients with histologically confirmed recurrent or metastaticovarian carcinoma, fallopian tube carcinoma, primary peritonealcarcinoma, cervical carcinoma, endometrial carcinoma, vulvar carcinoma, vaginal carcinoma, or carcinosarcoma of the ovary, endometrium or cervix who failed to respond to standard therapy or forwhom standard therapy was not available were eligible for this study.Eligibility criteria also included age more than and equal to 18 years; GOG performancestatues of 0 or 1; no treatment with investigational agents within30 days before commencing study treatment; and adequate hematopoietic (hemoglobin level more than and equal to 10 g/dL, absolute neutrophil count more than and equal to 1500/AL, platelet count more than and equal to 100, 000/AL), hepatic [bilirubin b1.5 mg/dL, aspartateand alanine aminotransaminases below the institutional upper limit ofnormal], and renal (creatinine below the institutional upper limit ofnormal) function. Up to three prior cytotoxic chemotherapy regimenswere permitted. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | A starting dose of 1mg/m(2) of intravenous topotecan days 1, 8 and 15 was combined with 25mg temsirolimus days 1, 8, 15 and 22 of a 28 day cycle. Patients with and without prior pelvic radiotherapy (RT) were doseescalated in separate cohorts. |
| Primary End Point: | DLT, MDT, and toxicity |
| Secondary End Point: | NA |
| Patients Number: | 15 |
| Trial Results |
| DLT_MTD: | Doselimiting toxicityincluded asymptomatic neutropenia and thrombocytopenia. |
| Objective Response Rate: | Nine of eleven patients were found to have stable disease attime of first evaluation; two patients were removed from the studydue to disease progression. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common drugrelated adverse events observed across all dose levels were fatigue (n=7), nausea (n=5), constipation (n=5), abdominal pain (n=4), vomiting(n=4) and mucositis (n=3). |
| Conclusions: | Doselimiting toxicity for the combination of temsirolimus with topotecan was myelosuppression. The regimen may be safe in women who have not previously received radiation, but full doses of each agent could not be administered in combination. |