ROCKIF Trial: Re-sensitization of Carboplatin-resistant Ovarian Cancer With Kinase Inhibition of FAK

Study Overview
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Brief Summary
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The purpose of the study is to investigate the combination VS-6063, carboplatin, and paclitaxel. in the treatment of patients with ovarian cancer. The study will evaluate whether this regimen is safe. The study will also evaluate whether the regimen can reduce the amount of cancerous cells in your body. If you agree, you will be treated with VS-6063 by mouth, as well as carboplatin and paclitaxel infusions. Carboplatin and paclitaxel are approved by the FDA for the treatment of ovarian cancer. VS-6063 is considered experimental because it is not approved by the FDA for the treatment of cancer.

Official Title
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ROCKIF Trial: Re-sensitization of Carboplatin-resistant Ovarian Cancer With Kinase Inhibition of FAK

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: VS-6063
* Drug: Paclitaxel
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal carcinoma, diagnosed within 6 months of completing their most recent platinum-containing chemotherapy. Patients with the following histologic cell types are eligible: Serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's Tumor, or adenocarcinoma not otherwise specified (N.O.S.) Must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound. This initial treatment may have included intraperitoneal therapy, high-dose therapy, consolidation, noncytotoxic agents or extended therapy administered after surgical or non-surgical assessment. Must have NOT received more than two total prior lines of cytotoxic chemotherapy for management of recurrent or persistent disease, including retreatment with initial chemotherapy regimens. May have received one additional non-cytotoxic regimen for management of recurrent or persistent disease according to the following definition: Non-cytotoxic (biologic or cytostatic) agents include (but are not limited to) hormones, monoclonal antibodies, cytokines, and small molecule inhibitors of signal transduction. Women of childbearing potential must have a negative serum pregnancy test prior to study entry and be practicing an effective form of contraception. Must have adequate: Bone marrow function Renal function Hepatic function Neurologic function Recovered from effects of recent surgery, radiotherapy, or chemotherapy. All persistent clinically significant toxicities from prior chemotherapy must be less than or equal to Grade 1. Free of active infection requiring antibiotics (with the exception of uncomplicated UTI). Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration. Exclusion Criteria: Platinum-refractory ovarian, fallopian tube, or primary peritoneal carcinoma. Known second primary or prior malignancy diagnosed within 5 years of study start date (other than previously treated non-melanoma skin cancer). Current treatment with chemotherapy or radiation therapy. Any prior therapy directed at the malignant tumor, including biologic and immunologic agents, must be discontinued at least three weeks prior to registration. History of treatment with known kinase inhibiting agents. History of gastrointestinal fistula, hemorrhage, perforation or peptic ulcer disease. Patients who are pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Defactinib (VS-6063) +Carboplatin/Paclitaxel<br> | Drug: VS-6063<br>* Phase 1: First 3 patient cohort: VS-6063 200 mg PO twice daily IF TOLERATED, Second 3 patient cohort: VS-6063 400 mg PO twice daily, Phase 2: VS-6063 400 mg PO twice daily of a 28 day cycle until disease progression or unacceptable toxicity.<br>* Other names: defactinib;Drug: Paclitaxel<br>* Phase 1: First 3 patient cohort: paclitaxel 80 mg/m2 infused IV continuously over 1 hour on days 1, 8, and 15 of a 28 day cycle. IF TOLERATED, Second 3 patient cohort: paclitaxel 80 mg/m2 infused IV continuously over 1 hour on days 1, 8, and 15 of a 28 day cycle. Phase 2: Paclitaxel 80 mg/m2 infused continuously over 1 hour on days 1, 8, and 15 of a 28 day cycle until disease progression or unacceptable toxicity.<br>Drug: Carboplatin<br>* Phase 1: First 3 patient cohort: carboplatin (AUC of 5 mg/mL/min) IV infused continuously over 1 hour on day 1 of a 28 day cycle. IF TOLERATED, Second 3 patient cohort: carboplatin (AUC of 5 mg/mL/min) IV infused continuously over 1 hour on day 1 of a 28 day cycle. Phase 2: carboplatin (AUC of 5 mg/mL/min) infused continuously over 1 hour on day 1 of a 28 day cycle until disease progression or unacceptable toxicity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety and tolerability of VS-6063 plus paclitaxel and carboplatin chemotherapy (Measured Via Adverse Events) | Measured Via Adverse Events | 4 years | 
| Objective response rate (ORR) | ORR by RECIST 1.1. | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the toxicity and adverse event profile of VS-6063 plus paclitaxel and carboplatin chemotherapy (Measured Via Adverse Events) | Measured Via Adverse Events | 4 years | 
| To describe health-related quality-of-life (QoL) outcomes of patients receiving VS-6063 plus paclitaxel and carboplatin chemotherapy. (Measured Via Questionnaire) | Measured Via Questionnaire | 4 years | 
| progression free survival (PFS) | PFS by RECIST 1.1. | 4 years | 
| overall survival (OS) | OS by RECIST 1.1. | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ovarian cancer, cancer, ovary, carboplatin, paclitaxel, VS-6063, primary peritoneal carcinoma, fallopian tube, defactinib