A two parts, biomarker study to identify genetic aberrations predictive for response on Everolimus in solid tumors without regular treatment options (CPCT*03)
- Conditions
- regular therapy refractory cancer10027655
- Registration Number
- NL-OMON40040
- Lead Sponsor
- Antoni van Leeuwenhoek Ziekenhuis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 80
-Subjects must provide written informed consent prior to performance of study*specific procedures or assessments, and must be willing to comply with treatment and follow*up.
- Inclusion in CPCT-02 study
- Age >= 18 years
- Diagnosis of malignant tumor showing progressive disease according to investigators opinion.
- WHO performance status of (0*2)
- Measurable disease allowing for volumetric measurements.
- No availability of standard of care systemic treatment options or patient refuses to receive standard of care chemotherapy treatment
- A female is eligible to enter and participate in this study if she is of: Non*childbearing potential (i.e., physiologically incapable of becoming pregnant) or by using adequate contraception
- Adequate organ system function.
- Previous treatment with mTOR inhibitors/pi3k inhibitors/AKT inhibitors
- Uncontrolled hypertension defined as RR > 160/95 mmHg
- Serious non*healing wound, ulcer or bone fracture
- Within 7 days of surgery (including minor procedures)
- Known and/or symptomatic intracerebral metastases
- Pregnancy or breast feeding, reproductive potential not using effective birth control methods
- Severe medical condition(s) prohibiting participation in the study
- Use of other investigational agents now or last 28 days prior to study treatment start
- Unable or unwilling to discontinue use of interacting medications or modify the dosing of interacting drugs for at least 14 days or five half*lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study
- Less than four weeks after regular treatment/ palliative radiotherapy.
- Prolongation of Fridericia corrected QT interval (QTc) > 480 milliseconds (msecs).
- Any severe and / or uncontrolled medical conditions such as:
1. Unstable angina pectoris, symptomatic congestive heart failure (Class III or IV congestive heart failure, as defined by the New York Heart Association), myocardial infarction <=6 months prior to enrollment, serious uncontrolled cardiac arrhythmia
2. Uncontrolled diabetes as defined by fasting serum glucose > 1.5 × ULN
3. Acute and chronic, active infectious disorders and nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy
4. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)
5. Significant symptomatic deterioration of lung function.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary endpoint first part:<br /><br>A set of approximately 1951 cancer related genes will be screened for mutations<br /><br>using next*generation sequencing (NGS). Progression free survival ratio<br /><br>(TTP1:TTP2) will be determined per patient as defined in section 5.2 and below.<br /><br>Exploratory analysis will be performed on aberrations predictive for respons on<br /><br>Everolimus.<br /><br><br /><br>Primary endpoint second part:<br /><br>Progression free survival ratio (PFR): the progression free survival ratio is<br /><br>defined as the time to a 30% volumetric increase in tumor volume or appearance<br /><br>of new lesions measured by CT scan without anti*neoplastic therapy (TTP1)<br /><br>divided by the time to a 30% volumetric increase in tumor volume or appearance<br /><br>of new lesions measured by CT scan from start mTOR inhibitor (Everolimus)<br /><br>(TTP2).</p><br>
- Secondary Outcome Measures
Name Time Method <p>Progression free survival: progression free survival is defined as time from<br /><br>registration to, either radiological or clinical disease progression or death<br /><br>from any cause.<br /><br>Disease control rate at 3 months: disease control rate (DCR) (DC = CR or PR or<br /><br>SD) as defined by RECIST 1.1 3 months after initiation of everolimus.<br /><br>(Median) overall survival: the (median) time from initiation of Everolimus to<br /><br>time of death or censored at the date of last follow*up.<br /><br>Toxicity: Toxicity will be assessed according to the Common Toxicity Criteria<br /><br>for Adverse Events (CTCAE) version v4.03: June 14, 2010 (Protocol Appendix 4,<br /><br>section 17.4).</p><br>