Olaparib as Salvage Treatment for Cisplatin-resistant Germ Cell Tumor
- Registration Number
- NCT02533765
- Brief Summary
This is open-label, single-arm, two-stage phase II trial of olaparib in patients with relapsed/refractory metastatic germ cell cancer. The primary objective is to evaluate the preliminary activity of Olaparib in GCT tumors. The secondary objective is to evaluate the safety of Olaparib in patients with cisplatin-refractory GCT.
- Detailed Description
This is a proof-of principle open-label, single-arm, two-stage phase II trial of olaparib 300 mg twice daily in patients with relapsed/refractory metastatic germ cell cancer. The study will recruit 10 patients, if no response is seen the study is terminated. If one or more responses are observed, further 19 patients (for a total of 29 patients) will be enrolled. If 4 or more of the first 29 evaluable patients have achieved objective response, further studies in patients with metastatic germ cell cancer are warranted.
The main inclusion criteria are:
* Patient with metastatic gonadal GCT or extragonadal GCT originating from retroperitoneum or mediastinum.
* Disease progression during cisplatin-based chemotherapy or disease progression or relapse after high-dose chemotherapy or disease progression or relapse after at least 2 different cisplatin-based regimens
* At least one measurable lesion that can be accurately assessed by CT/MRI/plain x-ray) at baseline and follow up visits.
The study will be analyzed on an intent-to-treat basis. Secondary parameters will be analyzed exploratively for the intent-to-treat population.
Correlations between with biomarkers (PAR, poly adenosine diphosphate-ribose polymerase (PARP-1), PTEN, XPA, ERCC1-3, XPF, FanD2, γ-H2AX) expression in paraffin-embedded tumor samples and clinical outcome will be performed in an exploratory intent. Plasma samples will be collected at baseline and at response/progression for possible retrospective biomarkers study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 18
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Olaparib Olaparib Olaparib 300mg twice daily continuously
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) Up to 30 months The percentage of patients whose cancer achieve either a partial response or a complete response.Tumor response will be assessed using CT scan or MRI of chest/abdomen using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and by tumor marker (AFP, betaHCG, LDH) measurements
- Secondary Outcome Measures
Name Time Method Evaluation of number, type and grade of Adverse Events Up to 30 months All patients will be evaluable for toxicity from the time of their first treatment with Olaparib
Overall survival (OS) Up to 30 months Time from enrolment to the date of death due to any cause. For subjects with no known date of death, survival time will be censored at the date of their last on-study assessment.
exploratory analysis of the association between PFS or OS and biomarkers Up to 30 months correlation between biomarkers (PAR, PARP-1, PTEN, XPA, ERCC1-3, XPF, FanD2, γ-H2AX) in paraffin-embedded tumor samples and plasma with clinical outcome (response, PFS, OS)
Progression free survival (PFS) Up to 30 months time from the date of starting of the treatment to the date of the first observation of documented disease progression or death due to any cause. Patients without tumor progression at the time of analysis will be censored at their last date of tumor evaluation.
Trial Locations
- Locations (2)
Istituto Nazionale Tumori IRCCS "Fondazione G.Pascale"
🇮🇹Napoli, Italy
U.O Oncologia Medica, IRST IRCCS
🇮🇹Meldola, FC, Italy