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

NCT01566279 | Completed

• 2 other identifiers: NL 37128.031.112011-002562-20
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 3

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Keywords

solid tumors; all comers; everolimus; biomarker; next generation sequencing

Outcome Measures

Primary Outcomes (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.

  Inclusion until earliest date of disease progression (defined as a 30% volumetric increase in tumorvolume or appearance of new lesions)

  An expected average of 5 months

Secondary Outcomes (4)

• Progression free survival

  An expected average of 4 months

• Disease control rate (DCR)

  At 3 months after initiation of everolimus

• Toxicity

  An expected average of 6 months

• Median overall survival

  An expected average of one year

Study Arms (1)

everolimus

OTHER

All patients in first part will receive everolimus 10mg q.d.

Drug: Everolimus

Interventions

Everolimus DRUG

All patients will receive everolimus 10mg q.d.

Also known as: Affinitor

everolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• UMC Utrecht: lead

Study Sites (3)

NKI-AVL

Amsterdam, North Holland, 1066 CX, Netherlands

Location

Erasmus Medical Center

Rotterdam, South Holland, 3075 EA, Netherlands

Location

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

Location

Related Publications (1)

• Cirkel GA, Weeber F, Bins S, Gadellaa-van Hooijdonk CG, van Werkhoven E, Willems SM, van Stralen M, Veldhuis WB, Ubink I, Steeghs N, de Jonge MJ, Langenberg MH, Schellens JH, Sleijfer S, Lolkema MP, Voest EE. The time to progression ratio: a new individualized volumetric parameter for the early detection of clinical benefit of targeted therapies. Ann Oncol. 2016 Aug;27(8):1638-43. doi: 10.1093/annonc/mdw223. Epub 2016 May 27.

  PMID: 27234642 DERIVED

Related Links

• Related Info

MeSH Terms

Interventions

Everolimus

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• 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 Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Investigator

Study Record Dates

• First Submitted: March 27, 2012
• First Posted: March 29, 2012
• Study Start: August 1, 2012
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2016
• Last Updated: March 9, 2018

Record last verified: 2018-03

Locations

NL (3)