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

Metastatic Cancer Clinical Trial

— MetAction  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02142036
• Other study ID #: MetAction
• Status: Completed
• Phase: Phase 2
• Start date: May 2014
• Est. completion date: August 2018

Study information

• Verified date: March 2019
• Source: Oslo University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: August 2018
• Est. primary completion date: August 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Metastatic Cancer
• Neoplasm Metastasis
• Neoplasms
• Neoplasms, Second Primary

Intervention

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.

Locations

Country	Name	City	State
Norway	Akershus University Hospital	Lillestrøm
Norway	The Norwegian Radium Hospital	Oslo

Sponsors (2)

Lead Sponsor	Collaborator
Oslo University Hospital	The Research Council of Norway

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall clinical benefit rate (ORR + stable disease [SD] = 6 months)		From date of initial response to date of first documented progression, assessed up to 24 months.
Other	ATI rate		From date of screening of first included patient until date of completion of screening phase, an expected time period of 24 months..
Other	PFS in ATI lesions only.		From date of initiation of study treatment until date of first documented progression in ATI lesions, assessed up to 24 months.
Other	Health Related Quality of Life (HRQoL) Questionnaire	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.
Other	Toxicity grade 3-5		From date of initiation of study treatment until date of follow-up visit, an expected average of 5 months.
Primary	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.	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	Overall response rate (ORR)	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.
Secondary	Overall survival (OS)		From date of initiation of study treatment until date of death, from any cause, assessed up to 24 months.