A Study to Identify a Biomarker Predictive for Response on Everolimus in Solid Tumors (CPCT-03) (CPCT-03)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01566279
Recruitment Status : Completed
First Posted : March 29, 2012
Last Update Posted : March 9, 2018
Information provided by (Responsible Party):
P.O. Witteveen, UMC Utrecht

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Unspecified Adult Solid Tumor, Protocol Specific Drug: Everolimus Not Applicable

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 73 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Two Parts, Biomarker Study to Identify Genetic Aberrations Predictive for Response on Everolimus in Solid Tumors Without Regular Treatment Options (CPCT-03)
Study Start Date : August 2012
Actual Primary Completion Date : November 2015
Actual Study Completion Date : November 2016

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
All patients in first part will receive everolimus 10mg q.d.
Drug: Everolimus
All patients will receive everolimus 10mg q.d.
Other Name: Affinitor

Primary Outcome Measures :
  1. analyse a set of 1951 genes for prediction of response measured by time to progression (TTP) ratio (defined as the TTP without drug: TTP on drug) on mTOR inhibition. [ Time Frame: An expected average of 5 months ]
    Inclusion until earliest date of disease progression (defined as a 30% volumetric increase in tumorvolume or appearance of new lesions)

Secondary Outcome Measures :
  1. Progression free survival [ Time Frame: An expected average of 4 months ]
    Time from initiation of everolimus to, either radiological (RECIST 1.1) or clinical disease progression or death from any cause.

  2. Disease control rate (DCR) [ Time Frame: At 3 months after initiation of everolimus ]
    Disease control rate (DCR) (DC = CR or PR or SD) as defined by RECIST 1.1 3 months after initiation of Everolimus.

  3. Toxicity [ Time Frame: An expected average of 6 months ]
    Toxicity will be assessed according to the Common Toxicity Criteria for Adverse Events (CTCAE) version v4.03: June 14, 2010

  4. Median overall survival [ Time Frame: An expected average of one year ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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:

    1. Unstable angina pectoris, symptomatic congestive heart failure 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
    5. 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:

    1. Topical applications (e.g. rash)
    2. Inhaled sprays (e.g. obstructive airways diseases),
    3. Eye drops
    4. Local injections (e.g. intra-articular) are allowed.
    5. Patients on stable low dose of corticosteroids for at least two weeks before enrollment are allowed in case of treatment of brain metastases .

Information from the National Library of Medicine

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 identifier (NCT number): NCT01566279

Amsterdam, Noord Holland, Netherlands, 1066 CX
Erasmus Medical Center
Rotterdam, Zuid Holland, Netherlands, 3075 EA
University Medical Center Utrecht
Utrecht, Netherlands, 3584 CX
Sponsors and Collaborators
UMC Utrecht
Principal Investigator: M.H.G. Langenberg, MD/PhD UMC Utrecht
Principal Investigator: N. Steeghs, MD/PhD NKI-AvL
Principal Investigator: M.J.A. de Jonge, MD/PhD Erasmus MC

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: P.O. Witteveen, Investigator, UMC Utrecht Identifier: NCT01566279     History of Changes
Other Study ID Numbers: NL 37128.031.11
2011-002562-20 ( EudraCT Number )
First Posted: March 29, 2012    Key Record Dates
Last Update Posted: March 9, 2018
Last Verified: March 2018

Keywords provided by P.O. Witteveen, UMC Utrecht:
solid tumors
all comers
next generation sequencing

Additional relevant MeSH terms:
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents