Vinorelbine in Relapsed Platinum Resistant or Refractory C5 High Grade Serous, Endometrioid, or Undifferentiated Primary Peritoneum, Fallopian Tube or Ovarian Cancer
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|ClinicalTrials.gov Identifier: NCT03188159|
Recruitment Status : Recruiting
First Posted : June 15, 2017
Last Update Posted : March 29, 2018
|Condition or disease||Intervention/treatment||Phase|
|Ovarian Cancer Fallopian Tube Cancer||Drug: Vinorelbine||Phase 2|
Background Therapeutic Information In ovarian cancer, several single agent phase II trials of vinorelbine in recurrent OC have shown variable response rates of 3 - 30%. However, previous studies have involved "all-comers" and no reported trials have selected patients based on confirmed pure HGSOC or a biomarker of relevance. Preclinical studies suggest that genes involved in microtubule dynamics, are significantly over-expressed in C5 tumours. Importantly, increased sensitivity was demonstrated of C5-like cell lines to tubulin depolymerising agents like vincristine and vinorelbine compared with microtubule stabilizing agents like paclitaxel. Subsequent studies on patient derived xenograft (PDX) models of C5 HGSOC (including platinum resistant models) showed responses for more than 50 days when treated with vinorelbine, providing preclinical proof that vinorelbine may be an effective therapeutic option in targeting the C5 subclass of HGSOC, including in platinum resistant or refractory disease.
Risk/ Benefit of Intervention Vinorelbine is a hemisynthetic vinca alkaloid that is traditionally administered intravenously via an infusion. The mechanism of action is disruption of microtubules by their reversible binding to tubulin resulting in mitotic spindle dissolution and metaphase arrest in dividing cells. This trial will afford patients with C5 relapsed platinum resistant or refractory HGSOC additional treatment options that may potentially have greater benefit than standard chemotherapy.
Tolerability The main dose limiting toxicity associated with IV vinorelbine in lung cancer is myelosuppression with Grade 3-4 neutropenia seen in up to 46% of patients. However, the febrile neutropenia rate was low at <5%. Mild to moderate gastrointestinal toxicity was observed with nausea and vomiting being the most common adverse effect. Grade 3/4 nausea or vomiting occurred in 7% - 17% of patients and primary prophylaxis is recommended. Neurotoxicity was also reported with the use of vinorelbine. Peripheral neuropathy was observed in up to 11% of patients,and neuroconstipation was documented to affect up to 24% of patients, however most of these cases were mild, grade 1-2. A similar toxicity profile was observed in patients with platinum resistant ovarian cancer treated with vinorelbine. Leukopenia was the most common dose limiting toxicity followed by anemia, fatigue and nausea.
Aim and Objectives of the trial The purpose of this trial is to determine if targeting platinum resistant or refractory C5 high-grade serous, high grade endometrioid or undifferentiated ovarian, primary peritoneal and fallopian tube with vinorelbine can improve patient outcomes.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of Intravenous Vinorelbine in Patients With Relapsed Platinum Resistant or Refractory C5 High Grade Serous, Endometrioid, or Undifferentiated Primary Peritoneum, Fallopian Tube or Ovarian Cancer (VIP)|
|Actual Study Start Date :||July 1, 2017|
|Estimated Primary Completion Date :||July 1, 2021|
|Estimated Study Completion Date :||July 1, 2022|
Experimental: IV Vinorelbine
IV Vinorelbine 25mg/m2
Vinorelbine 25 mg/m2 intravenously on day-1 and day-8 of a 3 week cycle to commence following confirmation of eligibility into the study for a maximum of 12 months, until disease progression, intolerable toxicity or withdrawal of patient consent (whichever event occurs first).
- Response rates [ Time Frame: 3 years ]To determine the activity of vinorelbine as defined by response rates when patients with recurrent platinum resistant or refractory C5 high-grade serous, endometrioid or undifferentiated ovarian, primary peritoneal or fallopian tube cancer are treated with IV vinorelbine based on RECISTv1.1
- Progression free survival [ Time Frame: 3 years ]To assess progression free survival when patients with recurrent platinum resistant C5 high-grade serous, endometrioid or undifferentiated ovarian, primary peritoneal and fallopian tube cancer are treated with IV vinorelbine
- Changes in the level of CA 125 [ Time Frame: 3 years ]A response according to CA 125 has occurred if there is at least a 50% reduction in CA 125 levels from a pretreatment sample. The response must be confirmed and maintained for at least 28 days. Patients can be evaluated according to CA 125 only if they have a pretreatment sample that is at least twice the upper limit of normal and within 2 weeks prior to starting treatment
- Adverse event profile [ Time Frame: 3 years ]To assess the adverse event profile of IV vinorelbine in this patient population
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03188159
|Contact: David SP Tan||(65) 6779 firstname.lastname@example.org|
|Peter MacCallum Cancer Centre||Recruiting|
|Contact: Linda Mileshkin, A/Prof (03) 8559 5000 Emaillinda.email@example.com|
|National University Hospital||Recruiting|
|Singapore, Singapore, 164119|
|Contact: David SP Tan 65 6779 5555 firstname.lastname@example.org|
|Principal Investigator:||David Tan||National University Hospital, Singapore|