Off-label Use of Anti-cancer Drugs in Norway -a Prospective Cohort Study

Off-label drug use, where a marketed drug is used outside its approved indication, may allow early access to new and promising treatments. However, its use can be a source of controversy, due to limited evidence for clinical benefit and lack of cost/QALY-estimates, leading to challenging prioritization issues. The number of drugs suitable for off-label use is expected to further increase in the coming years, owing to the rapid progress in the field of oncology, in particular with the current era of precision medicine and targeted therapies. This also challenges the traditional method of running clinical trials, with eligible patient populations commonly being small, underpinning the importance of gaining supplementary real-world evidence from well performed observational studies.

This prospective observational study will therefore assess real-world outcomes of patients treated with off-label anti-cancer drugs, including efficacy in terms of response rates, time to progression/relapse measures and survival; patient-reported outcome measures (PROMS) and self-reported side-effects/toxicity; as well as collecting blood samples for a biobank for further translational research. Further, the study will give a descriptive analysis of the current practice of off-label use of anti-cancer drugs in Norway, including prevalence estimation and health care related cost analyses.

Study Overview

• Status: Recruiting
• Conditions: Cancer

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Knut Smeland, PhD/MD; Phone Number: +4722934000; Email: knusme@ous-hf.no
• Study Contact Backup: Name: Tormod Guren, PhD/MD; Phone Number: +4722934000; Email: uxtour@ous-hf.no

Study Locations

• Norway
  • Oslo, Norway, 0379
    • Recruiting
    • Oslo University Hospital
    • Contact: Knut Smeland, PhD/MD; Phone Number: +4722934000; Email: knusme@ous-hf.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Any patient accepted by the leadership in the Department of Oncology at OUH to receive anti-cancer treatment off-label from the date of start of the study is eligible for inclusion. Of note, this does not include off-label use of drugs used for supportive care.

Description

Inclusion Criteria:

• Verified cancer diagnosis (based on radiological, histological/cytological or operative evidence).
• Treatment with off-label anti-cancer drug.
• Age ≥ 18 years
• Able to provide written informed consent.

Exclusion Criteria:

• None

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS).	Time from date of inclusion until the date of first documented progression or date of death from any cause, whichever come first, according to RECIST v1.1	Assessed up to 2 years after end of inclusion
Patients questionnaire EORTC QLQ-C30	Assessment of patients reported quality of life, as measured by EORTC QLC30	Assessed from inclusion until 2 years after end of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective tumor response rate (ORR)	Defined as the proportion of patients with an objective tumor response (either partial response [PR] or complete response [CR] using RECIST v1.1) response (DR), time to next treatment and overall survival (OS)	Assed through study completion, an average of 1 year
Duration of response (DR)	Duration of response among patients with an objective response, according to RECIST v1.1	Assed through study completion, an average of 1 year
Time to next treatment (TTNT)	Time from inclusion to institution og next therapy	Assed through study completion, an average of 1 year
Overall survival (OS)	Time from date of inclusion until the date of death from any cause	Assessed up to 2 years after end of inclusion
Fatigue	Assessment of patient reported outcomes, as measured by the Chalder Fatigue Questionnaire (FQ)	From inclusion until 2 years after end of treatment
Depression	Assessment of patient reported outcomes, as measured by the patient health questionnaire (PHQ-9)	From inclusion until 2 years after end of treatment
Pain intensity	Assessment of patient reported outcomes, as measured by an 11 point Numerical Rating Scale (NRS) for pain intensity	From inclusion until 2 years after end of treatment
Adverse event	Patients files and self-report. Classified according to CTCAE v 5.0 and MedDRA	From inclusion until 2 years after end of treatment
Quality adjusted life years (QALYs)	Patient self reported EQ-5D	From inclusion until 2 years after end of treatment

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Investigators: Principal Investigator: Knut Smeland, PhD/MD, Oslo University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: June 25, 2020
• First Submitted That Met QC Criteria: June 30, 2020
• First Posted (Actual): July 7, 2020

Study Record Updates

• Last Update Posted (Actual): October 31, 2023
• Last Update Submitted That Met QC Criteria: October 30, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Off Label Use
• Other Study ID Numbers: Off Label Study protocol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No