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

Primary Purpose

Metastatic Cancer

Status
Completed
Phase
Phase 2
Locations
Norway
Study Type
Interventional
Intervention
EMA-approved ATI based targeted therapy
Sponsored by
Oslo University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Cancer focused on measuring Metastatic disease, Metastasis, Targeted therapy, Solid tumor, Personalized medicine, N-of-1 trial

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Akershus University Hospital
  • The Norwegian Radium Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ATI based targeted therapy.

Arm Description

EMA-approved ATI based targeted therapy. Patients will receive therapy based on molecular aberrations identified in the metastatic lesion.

Outcomes

Primary Outcome Measures

Progression-free survival (PFS)
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.

Secondary Outcome Measures

Overall response rate (ORR)
The sum of partial responses (PS) plus complete responses (CR).
Overall survival (OS)

Full Information

First Posted
April 13, 2014
Last Updated
March 12, 2019
Sponsor
Oslo University Hospital
Collaborators
The Research Council of Norway
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1. Study Identification

Unique Protocol Identification Number
NCT02142036
Brief Title
N-of-1 Trial: Actionable Target Identification in Metastatic Cancer for Palliative Systemic Therapy
Acronym
MetAction
Official Title
N-of-1 Trial of Actionable Target Identification in Metastatic Cancer for Palliative Systemic Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
May 2014 (Actual)
Primary Completion Date
August 2018 (Actual)
Study Completion Date
August 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Oslo University Hospital
Collaborators
The Research Council of Norway

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Cancer
Keywords
Metastatic disease, Metastasis, Targeted therapy, Solid tumor, Personalized medicine, N-of-1 trial

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ATI based targeted therapy.
Arm Type
Experimental
Arm Description
EMA-approved ATI based targeted therapy. Patients will receive therapy based on molecular aberrations identified in the metastatic lesion.
Intervention Type
Drug
Intervention Name(s)
EMA-approved ATI based targeted therapy
Other Intervention Name(s)
Cetuximab, Panitumumab, Gefitinib, Erlotinib, Crizotinib, Trastuzumab, Lapatinib, Imatinib, Dasatinib, Nilotinib, Vemurafenib, Everolimus, Temsirolimus, Sunitinib, Ruxolitinib, Vandetanib., Afatinib, Dabrafenib
Intervention Description
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.
Primary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
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.
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.
Secondary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
The sum of partial responses (PS) plus complete responses (CR).
Time Frame
From date of initiation of study treatment until the date of first documented progression, assessed up to 24 months.
Title
Overall survival (OS)
Time Frame
From date of initiation of study treatment until date of death, from any cause, assessed up to 24 months.
Other Pre-specified Outcome Measures:
Title
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.
Title
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..
Title
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.
Title
Health Related Quality of Life (HRQoL) Questionnaire
Description
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.
Time Frame
From date of initiation of study treatment until date of end of study visit, an expected average of 4 months.
Title
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kjersti Flatmark, MD PhD
Organizational Affiliation
Oslo University Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Svein Dueland, MD
Organizational Affiliation
Oslo University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Anne Hansen Ree, Prof. MD PhD
Organizational Affiliation
University Hospital, Akershus
Official's Role
Principal Investigator
Facility Information:
Facility Name
Akershus University Hospital
City
Lillestrøm
ZIP/Postal Code
1478
Country
Norway
Facility Name
The Norwegian Radium Hospital
City
Oslo
ZIP/Postal Code
0379
Country
Norway

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
35943168
Citation
Ree AH, Maelandsmo GM, Flatmark K, Russnes HG, Gomez Castaneda M, Aas E. Cost-effectiveness of molecularly matched off-label therapies for end-stage cancer - the MetAction precision medicine study. Acta Oncol. 2022 Aug;61(8):955-962. doi: 10.1080/0284186X.2022.2098053. Epub 2022 Aug 9.
Results Reference
derived
PubMed Identifier
32208873
Citation
Ree AH, Nygaard V, Boye K, Heinrich D, Dueland S, Bergheim IR, Johansen C, Beiske K, Negard A, Lund-Iversen M, Nygaard V, Hovig E, Nakken S, Nasser S, Julsrud L, Reisse CH, Ruud EA, Kristensen VN, Florenes VA, Geitvik GA, Lingjaerde OC, Borresen-Dale AL, Russnes HG, Maelandsmo GM, Flatmark K. Molecularly matched therapy in the context of sensitivity, resistance, and safety; patient outcomes in end-stage cancer - the MetAction study. Acta Oncol. 2020 Jul;59(7):733-740. doi: 10.1080/0284186X.2020.1742377. Epub 2020 Mar 25.
Results Reference
derived

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

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