N-of-1 Trial: Actionable Target Identification in Metastatic Cancer for Palliative Systemic Therapy (MetAction)

March 12, 2019 updated by: Kjersti Flatmark, Oslo University Hospital

N-of-1 Trial of Actionable Target Identification in Metastatic Cancer for Palliative Systemic Therapy

The metastatic lesions may be very different from the primary tumor because of intrinsic tumor heterogenity, clonal selection through metastatic process and following previous cytotoxic treatments. Metastatic tumor harboring actionable targets or signaling pathways may respond to inhibitory agents directed against specific aberrations irrespective of tumor origin. In the MetAction study, patients will receive therapy based on molecular aberrations in the metastatic lesions, actionable target identification (ATI), rather than on histological tumor type.

The ATI rate in an unselected metastatic patient population is uncertain, and response rates associated with ATI based targeted therapy have hardly been reported. In this perspective, The MetAction study is essentially a feasibility study aiming to tailor metastatic cancer therapy based on genomic profiles.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Recognizing the rapidly increasing number of drugs targeting specific molecular aberrations in cancer, it is necessary to define rational strategies to make such treatment available to Norwegian cancer patients.These targeted drugs are extremely costly and have significant side effects, although presumably to a lesser extent than many of the classic cytotoxic drugs available. Thus, in the interest of the patient in question and the society in general, it is important to give the right drug to the right patient and to the presumably right time in the disease course.

Hitherto, most of the drugs in question are given in the palliative setting, i.e. to patients with disseminated metastatic disease. The metastatic lesion may be very different from the primary tumor, and hence, it is rational to analyze the tumor to be treated, the metastatic lesion(s), for the presence of molecular aberrations, rather than basing treatment decisions on molecular features known to be present in a particular tumor type or in the primary tumor.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Norway
      • Lillestrøm, Norway, 1478
        • Akershus University Hospital
      • Oslo, Norway, 0379
        • The Norwegian Radium Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Metastatic cancer and progression by RECIST 1.0 evaluated by internal review on at least one prior regimen of established palliative systemic therapies for advanced disease and eligibility for repeat biopsy sampling. The patient must have received ≥6 weeks of the previous treatment. Only patients who have no other standard treatment option or were the treatment option is considered to offer the patients only minor benefit may be included in the study.
  • Radiological evaluation intervals on last prior therapy (period A) must have been 6 to 12 weeks.
  • At least one measurable lesions (>10mm on CT-scan) according to RECIST 1.0.
  • Age ≥ 18 years. Eastern Cooperative Oncology Group (ECOG) performance status 1 or lower.
  • Life expectancy of more than 3 months.
  • Adequate bone marrow function without current use of colony-stimulating factors: Neutrophils ≥1.5 x109/l; Platelets ≥100 x109/l; Hb >10 g/dl, INR within normal level.
  • Adequate liver function: AST/ALT ≤5x ULN; Bilirubin ≤2x ULN, albumin >30 g/l.
  • Adequate renal function: Creatinine ≤1.5x ULN.
  • Be able to use recommended dose of the selected targeted therapy as described in the drug specific SPC.
  • Be able to comply with the protocol.
  • Fertile men and women must be willing to use effective contraceptives.
  • Provide written (signed) informed consent to participate in the trial prior to any trial specific screening procedures.

Exclusion Criteria:

  • Metastatic disease from more than one malignancy.
  • Untreated or symptomatic brain metastasis (patients must be symptom-free without the use of corticosteroids).
  • Any reason why, in the opinion of the investigator, the patient should not participate.
  • Pregnancy.
  • Breastfeeding
  • Anticoagulation with coumarin derivatives.
  • Radiation therapy within 4 weeks of start of treatment.
  • Need to use medications contraindicated according to SPC of the different drugs.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ATI based targeted therapy.
EMA-approved ATI based targeted therapy. Patients will receive therapy based on molecular aberrations identified in the metastatic lesion.
Drug: EMA-approved ATI based targeted therapy
All drugs that may be used in the study are approved by EMA for treatment of disseminated cancer in the palliative setting, but not for the particular tumor type in question.
Other Names:
  • Panitumumab
  • Everolimus
  • Trastuzumab
  • Lapatinib
  • Imatinib
  • Gefitinib
  • Ruxolitinib
  • Sunitinib
  • Cetuximab
  • Temsirolimus
  • Dabrafenib
  • Afatinib
  • Erlotinib
  • Dasatinib
  • Nilotinib
  • Vemurafenib
  • Crizotinib
  • Vandetanib.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: From date of initiation of study treatment until the date of first documented progression or date of death, from any cause, whichever came first, assessed up to 24 months.
Comparing the PFS using therapy selected by ATI in a patient's tumor (period B) with the PFS for the most recent therapy on which the patient had just experienced progression (period A). The ATI-selected therapy is defined as having benefit for the patient if PFS period B/PFS in period A ratio is ≥ 1.3.
From date of initiation of study treatment until the date of first documented progression or date of death, from any cause, whichever came first, assessed up to 24 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate (ORR)
Time Frame: From date of initiation of study treatment until the date of first documented progression, assessed up to 24 months.
The sum of partial responses (PS) plus complete responses (CR).
From date of initiation of study treatment until the date of first documented progression, assessed up to 24 months.
Overall survival (OS)
Time Frame: From date of initiation of study treatment until date of death, from any cause, assessed up to 24 months.
From date of initiation of study treatment until date of death, from any cause, assessed up to 24 months.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall clinical benefit rate (ORR + stable disease [SD] ≥ 6 months)
Time Frame: From date of initial response to date of first documented progression, assessed up to 24 months.
From date of initial response to date of first documented progression, assessed up to 24 months.
ATI rate
Time Frame: From date of screening of first included patient until date of completion of screening phase, an expected time period of 24 months..
From date of screening of first included patient until date of completion of screening phase, an expected time period of 24 months..
PFS in ATI lesions only.
Time Frame: From date of initiation of study treatment until date of first documented progression in ATI lesions, assessed up to 24 months.
From date of initiation of study treatment until date of first documented progression in ATI lesions, assessed up to 24 months.
Health Related Quality of Life (HRQoL) Questionnaire
Time Frame: From date of initiation of study treatment until date of end of study visit, an expected average of 4 months.
Assessed by the subject questionnaire EORTC Quality of Life Questionnaire Core 30 (QlQ-C30) at baseline, every 8 week during treatment and at end of study visit.
From date of initiation of study treatment until date of end of study visit, an expected average of 4 months.
Toxicity grade 3-5
Time Frame: From date of initiation of study treatment until date of follow-up visit, an expected average of 5 months.
From date of initiation of study treatment until date of follow-up visit, an expected average of 5 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Oslo University Hospital

Collaborators

The Research Council of Norway

Investigators

  • Study Chair: Kjersti Flatmark, MD PhD, Oslo University Hospital
  • Principal Investigator: Svein Dueland, MD, Oslo University Hospital
  • Principal Investigator: Anne Hansen Ree, Prof. MD PhD, University Hospital, Akershus

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2014

Primary Completion (Actual)

August 1, 2018

Study Completion (Actual)

August 1, 2018

Study Registration Dates

First Submitted

April 13, 2014

First Submitted That Met QC Criteria

May 19, 2014

First Posted (Estimate)

May 20, 2014

Study Record Updates

Last Update Posted (Actual)

March 13, 2019

Last Update Submitted That Met QC Criteria

March 12, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MetAction

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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