Last updated: 11/03/2018 21:58:10
Adjusting for treatment crossover in the METRIC trial comparing trametinib to dacarbazine using the ITT population (based on final data cut off)
Clinicaltrials.gov ID
Not applicable
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: Adjusting for treatment crossover in the METRIC trial comparing trametinib to dacarbazine using the ITT population (based on final data cut off)
Trial description: METRIC is a randomized, multi-centre Phase III study to evaluate efficacy and safety of trametinib compared to standard chemotherapy (DTIC or paclitaxel) in patients with advanced or metastatic BRAF V600E/K mutation-positive melanoma. Treatment crossover occurs when patients in the control group of a clinical trial are allowed to switch onto the experimental treatment at some point during follow-up. In the METRIC trial, patients in the chemotherapy group were permitted to switch onto trametinib following disease progression. If an “intention to treat” analysis is conducted on data confounded by crossover, the estimate of the overall survival (OS) advantage associated with the new treatment will be biased. If control group patients that cross over benefit from the new treatment, measures of average OS in the control group (for example, means, or medians) will be higher than would have been observed if treatment crossover had not occurred. This will result in the OS advantage of the new treatment being underestimated. This is particularly important in the context of economic evaluation because survival estimates are used in cost-effectiveness analyses used to support health technology assessment submissions, and treatment crossover is likely to cause the cost-effectiveness of the new treatment to be underestimated (the incremental cost-effectiveness ratio (ICER) is likely to be overestimated). Hence, it is important to adjust for any effects of treatment crossover. The study objective was to estimate the treatment effect of trametinib compared to DTIC for OS that would have been observed if treatment crossover had not occurred in the METRIC trial. Different methods (RPSFTM, IPE, IPCW and two-stage statistical methods) will be applied to adjust for treatment crossover using the ITT population and DTIC as the comparator from the May 2014 dataset. Results will be summarized as HRs (with 95% CIs).Validity and appropriateness of each method will be assessed with respect to their assumptions and study characteristics.
Primary purpose:
Not applicable
Trial design:
Not applicable
Masking:
Not applicable
Allocation:
Not applicable
Primary outcomes:
Overall survival
Timeframe: Varies by subject (time to death or censoring)
Secondary outcomes:
Not applicable
Interventions:
Enrollment:
1
Primary completion date:
Not applicable
Observational study model:
Other
Time perspective:
Other
Clinical publications:
Not applicable
Medical condition
Melanoma
Product
dacarbazine, trametinib
Collaborators
Not applicable
Study date(s)
November 2014 to January 2015
Type
Observational
Phase
Not applicable
Participation criteria
Sex
Female & Male
Age
21 - 85 Year
Accepts healthy volunteers
none
- For METRIC trial key inclusion criteria included:
- Histologically confirmed, Stage III unresectable (Stage IIIC) or metastatic (Stage IV) cutaneous melanoma, which is also determined to be BRAF V600E/K mutation positive by the central reference laboratory.
Inclusion and exclusion criteria
Inclusion criteria:
- For METRIC trial key inclusion criteria included:
- Histologically confirmed, Stage III unresectable (Stage IIIC) or metastatic (Stage IV) cutaneous melanoma, which is also determined to be BRAF V600E/K mutation positive by the central reference laboratory.
- Subjects may have received no prior treatment or up to 1 prior regimen of chemotherapy for advanced or metastatic melanoma.
- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
- Adequate screening organ function
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. For METRIC trial key exclusion criteria included:
- Any prior use of BRAF/MEK inhibitors, or ipilimumab in the advanced or metastatic setting.
- Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within the last 21 days. Chemotherapy given daily or weekly without the potential for delayed toxicity within the last 14 days.
- History of other malignancy. Subjects who had been disease-free for 3 years or subjects who had a history of completely resected non-melanoma skin cancer were eligible.
- Any serious and/or unstable pre-existing medical (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance to the study procedures.
- Brain metastases with the following exceptions that are ALL confirmed by the GSK Medical Monitor: -- All known lesions must be previously treated with surgery or stereotactic radiosurgery (prior whole brain radiotherapy is not allowed), and -- Brain lesion(s), if still present, must be confirmed stable (i.e. no increase in lesion size), or if no longer present, must be confirmed as no evidence of disease, for 90 days prior to randomization (must be documented with two consecutive MRI or CT scans at least 60 days apart using contrast), and -- Asymptomatic with no corticosteroids requirement for ≥ 30 days prior to randomization, and -- No enzyme-inducing anticonvulsants for ≥ 30 days prior to randomization.
- History or evidence of cardiovascular risk
- History or current evidence / risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
Trial location(s)
This study does not involve prospective enrollment of participants.
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Study complete
Actual primary completion date
Not applicable
Actual study completion date
2015-23-01
Plain language summaries
Not applicable. GSK’s transparency policy provides for Plain Language Summaries for Interventional studies.
Additional information about the trial
Not applicable
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