| General information |
| Database: | DB00530 |
| Objective: | Patients with persistent/recurrent epithelial ovarian cancer/primary peritoneal cancer (EOC/PPC) have limited treatment options. AKT and PI3K pathway activation is common in EOC/PPC, resulting in constitutive activation of downstream mTOR. The GOG conducted a phase II evaluation of efficacy and safety for the mTOR inhibitor, temsirolimus in EOC/PPC and explored circulating tumor cells (CTC) and AKT/mTOR/downstream tumor markers. |
| Authors: | Behbakht K, et al |
| Title: | Phase II trial of the mTOR inhibitor, temsirolimus and evaluation of circulating tumor cells and tumor biomarkers in persistent and recurrent epithelial ovarian and primary peritoneal malignancies: a Gynecologic Oncology Group study. |
| Journal: | Gynecol Oncol. |
| Year: | 2011 |
| PMID: | 21752435 |
| Trial Design |
| Clinical Trial Id: | NCT00429793 |
| Agent: | temsirolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | ovarian, primary peritoneal, or fallopian tube carcinoma, |
| Cancer Subtype: | advanced epithelial ovarian and primary peritoneal malignancies |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase II trial |
| Key Patients Feature: | Women with recurrent/persistent EOC/PPC on review of the surgical pathology report andwith RECIST measurable disease who had received 1-3 prior cytotoxic regimens wereeligible. Patients must have had at least one prior platinumbased regimen and, if enrolledfollowing primary treatment, must have had a platinumfree interval of <12 months.Cytostatic agents were allowed with primary treatment but not for recurrences. Patients musthave had adequate bone marrow function with absolute neutrophil count more than and equal to 1, 500/mcl, platelets more than and equal to 100, 000/mcl as well as creatinine less than and equal to 1.5x institutional upper limit of normal (ULN), bilirubin less than and equal to 1.5xULN, SGOT and alkaline phosphatase less than and equal to 2.5xULN, neuropathy less than and equal to CommonCriteria for Adverse Events (CTCAE) v3.0 grade 1, fasting cholesterol <350 mg/dl, andfasting triglycerides <400 mg/dl |
| Biomarker: | CTC, and AKT/mTOR/downstream markers |
| Biomark Analysis: | Suggested associations were between cyclin D1 and PFS more than and equal to 6 months, PFS or survival; positive CTC pretreatment and lack of response; and high CTC expression of M30 and PFS more than and equal to 6 months/longer PFS. |
| Control Group Info: | single arm |
| Treatment Info: | pts were treated with 25mg weekly IV temsirolimus until progression or intolerable toxicity. CellSearch system was used to examine CTC, and AKT/mTOR/downstream markers were evaluated by archival tumor immunohistochemistry. Kendall's taub correlation coefficient (r) and Cox regression modeling were used to explore marker associations with baseline characteristics and outcome. |
| Primary End Point: | progression free survival (PFS) more than and equal to 6months, tumor response, and toxicity. |
| Secondary End Point: | NA |
| Patients Number: | 60 |
| Trial Results |
| DLT_MTD: | Grade 3/4 adverse events includedmetabolic(8), gastrointestinal(8), pain(6), constitutional(5) and pulmonary(4). |
| Objective Response Rate: | Of 54 eligible andevaluable patients, 24.1% (90%CI 14.9%-38.6%) had PFS more than and equal to 6 months (median 3.1 months), 9.3%(90%CI 3.7%-23.4%) experienced a partial response |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 3.2 months |
| Median OS A vs. C: | 11.6 months |
| Adverse Event(agent arm): | Grade 3/4 adverse events included metabolic(8), gastrointestinal(8), pain(6), constitutional(5) and pulmonary(4). |
| Conclusions: | Temsirolimus appears to have modest activity in persistentrecurrent EOCPPC; hotheyver, PFS is just below that required to warrant inclusion inphase III studies in unselected patients. Cyclin D1 as a selection marker and CTC measures merit further study. |