A Study to Identify a Biomarker Predictive for Response on Everolimus in Solid Tumors (CPCT-03)
Verified February 2014 by UMC Utrecht
Information provided by (Responsible Party):
Martijn P. Lolkema, UMC Utrecht
First received: March 27, 2012
Last updated: February 23, 2014
Last verified: February 2014
The investigators hypothesize that certain mutations in the individual cancer genomes will predict response to Everolimus therapy. To identify possible genetic mutations that affect tumor response to Everolimus the investigators will obtain sequence analysis of tumors from all patients that will be treated with Everolimus in this study. Moreover, the investigators performed a systematic review of the currently available data to identify mutations that could be predictive for increased mTOR activity in cancer cells. These mutations have been described to lead to mTOR activation but their predictive value for response to Everolimus therapy remains unclear. The investigators will use the data generated in the investigators own prospective treatment study and the data from literature to select patients for entry into a second part of this trial. In this part the investigators want to test the hypothesis that selecting patients based on their specific genetic mutations increases the likelihood of response.
Unspecified Adult Solid Tumor, Protocol Specific
||Intervention Model: Single Group Assignment
Masking: Open Label
||A Two Parts, Biomarker Study to Identify Genetic Aberrations Predictive for Response on Everolimus in Solid Tumors Without Regular Treatment Options (CPCT-03)
Primary Outcome Measures:
Secondary Outcome Measures:
- Progression free survival [ Time Frame: An expected average of 4 months ] [ Designated as safety issue: No ]
Time from initiation of everolimus to, either radiological (RECIST 1.1) or clinical disease progression or death from any cause.
- Disease control rate (DCR) [ Time Frame: At 3 months after initiation of everolimus ] [ Designated as safety issue: No ]
Disease control rate (DCR) (DC = CR or PR or SD) as defined by RECIST 1.1 3 months after initiation of Everolimus.
- Toxicity [ Time Frame: An expected average of 6 months ] [ Designated as safety issue: Yes ]
Toxicity will be assessed according to the Common Toxicity Criteria for Adverse Events (CTCAE) version v4.03: June 14, 2010
- Median overall survival [ Time Frame: An expected average of one year ] [ Designated as safety issue: No ]
The (median) time from initiation of Everolimus to time of death or censored at the date of last follow-up. First analysis of overall survival will be performed within one year after inclusion of last subject.
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||June 2014 (Final data collection date for primary outcome measure)
All patients in first part will receive everolimus 10mg q.d.
All patients will receive everolimus 10mg q.d.
Other Name: Affinitor
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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 the 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
- Adequate organ system function as defined in the protocol
- Fasting serum cholesterol ≤ 300 mg/dl or 7.75 mmol/L and fasting triglycerides ≤ 2.5 × ULN.
- 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 (QTcF) > 480 milliseconds
Any severe and / or uncontrolled medical conditions such as:
- Unstable angina pectoris, symptomatic congestive heart failure myocardial infarction ≤6 months prior to enrollment, serious uncontrolled cardiac arrhythmia
- Uncontrolled diabetes as defined by fasting serum glucose > 1.5 × ULN
- 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
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drugs
- Significant symptomatic deterioration of lung function.
- Active, bleeding diathesis, or on oral anti-vitamin K medication (except low dose warfarin and acetylsalicylic acid or equivalent, as long as the INR is < 2.0)
- Patients with a known history of HIV seropositivity
- Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A within the last 5 days prior to enrollment
Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use, at the time of study entry except in cases outlined below:
- Topical applications (e.g. rash)
- Inhaled sprays (e.g. obstructive airways diseases),
- Eye drops
- Local injections (e.g. intra-articular) are allowed.
- Patients on stable low dose of corticosteroids for at least two weeks before enrollment are allowed in case of treatment of brain metastases .
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01566279
|Amsterdam, Noord Holland, Netherlands, 1066 CX |
|Erasmus Medical Center
|Rotterdam, Zuid Holland, Netherlands, 3075 EA |
|University medical center Utrecht
|Utrecht, Netherlands, 3584 CX |
|Sub-Investigator: G.A. Cirkel, MD |
||M.P.J.K. Lolkema, MD/PhD
||N. Steeghs, MD/PhD
||A. Matthijssen, MD/PhD
No publications provided
||Martijn P. Lolkema, MD/PhD, UMC Utrecht
History of Changes
|Other Study ID Numbers:
||NL 37128.031.11, 2011-002562-20
|Study First Received:
||March 27, 2012
||February 23, 2014
||Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Keywords provided by UMC Utrecht:
next generation sequencing
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on July 20, 2014
Physiological Effects of Drugs