Ignite Creation Date:
2024-05-06 @ 3:56 AM
Last Modification Date:
2024-10-26 @ 11:41 AM
Study NCT ID:
NCT02410863
Status:
TERMINATED
Last Update Posted:
2020-10-14
First Post:
2015-04-02
Brief Title:
Biopsy- and Biology-driven Optimization of Targeted Therapy in Subjects With Advanced Melanoma
Sponsor:
Prof Dr med Dirk Schadendorf
Organization:
University Hospital Essen
Study Overview
Official Title:
Biopsy- and Biology-driven Optimization of Targeted Therapy of Metastatic Melanoma in BRAF Inhibitor Non-pretreated and Pretreated Subjects With Advanced Non-resectable STAGE IIIC or Metastatic StAGE IV BRAF Mutation-positive Melanoma
Status:
TERMINATED
Status Verified Date:
2020-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
lack of recruitment due to changed therapy options
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BOTTOM
Brief Summary:
This is an open-label multi-center clinical phase II study to explore the correlation of the genetic make-up of the treated tumor before start of therapy and to correlate clinical response at 8 weeks as well as metabolic response at 2 and 8 weeks with genetic features of the tumor
It will be conducted as a rationale optimization of targeted therapy in BRAF naïve and pretreated patients
Prerequisite for all patients is the availability of tumor sample at start of treatment in order to determine the underlying driver mutation BRAF mutational status as well as molecular composition by next generation sequencing NGS and assessable lesions for biopsy at week 2 Melanoma patients in stage III non-resectable and stage IV are sorted into Cohort A or B according to their previous BRAF-treatment and treated with dabrafenib and trametinib cohort A and B
It will be conducted as a rationale optimization of targeted therapy in BRAF naïve and pretreated patients
Prerequisite for all patients is the availability of tumor sample at start of treatment in order to determine the underlying driver mutation BRAF mutational status as well as molecular composition by next generation sequencing NGS and assessable lesions for biopsy at week 2 Melanoma patients in stage III non-resectable and stage IV are sorted into Cohort A or B according to their previous BRAF-treatment and treated with dabrafenib and trametinib cohort A and B
Detailed Description:
In this open-label multi-center clinical phase II study melanoma patients in stage III non-resectable and stage IV are sorted into Cohort A or B according to their previous BRAF-treatment
Cohort A BRAFi naïve Patients who have not received prior BRAFi or MEKi-therapy Dabrafenib BRAFi and trametinib MEKi will be administered orally at their recommended doses for combination therapy of 150 mg twice daily BID and 2 mg daily QD Clinical endpoint is clinical response at week 8 Metabolic response will be assessed at week 2 and 8 Treatment will continue until disease progression death unacceptable toxicity or withdrawal of consent
Cohort B BRAFi MEKi rechallenge Patients with CRPR as best response to previous BRAFi MEKi combination therapy discontinuation of this therapy after progression and different therapy for 3 months prior to enrollment
These patients will receive dabrafenib and trametinib at their recommended combination therapy doses of 150 mg twice daily BID and 2 mg daily QD
Treatment will continue until disease progression death unacceptable toxicity or withdrawal of consent
Survival will be assessed every 3 months after the final dose of BRAFi MEKi until the end of the follow-up phase for the individual patient
Follow up phase for each subject is 1 year following first treatment dose End of study will be at recruitment finished plus 1 year post start of treatment of last patient thus ensuring that 1 year survival rate can be estimated
Biopsies taken before start of treatment after 2 weeks - 4 days and after progressive disease will be analyzed by Next generation sequencing NGS immunohistochemistry IHC phosphorplex Luminex as well as by reverse phase protein array in order to determine the magnitude of suppression of downstream signaling as well as reactivation of adaptative mechanisms
Rebiopsy is mandatory after 2 weeks and in case of progressive disease in order to determine mechanisms of adaptation of the signaling pathway downstream
The experimental molecular data will be analyzed in correlation with clinical response at week 8 defined as partial or complete response according to RECIST and metabolic responses at weeks 2 and 8 responders are defined as those patients with changes of 66 in the Standard Uptake value SUVmax between interim PET and baseline PET
Cohort A BRAFi naïve Patients who have not received prior BRAFi or MEKi-therapy Dabrafenib BRAFi and trametinib MEKi will be administered orally at their recommended doses for combination therapy of 150 mg twice daily BID and 2 mg daily QD Clinical endpoint is clinical response at week 8 Metabolic response will be assessed at week 2 and 8 Treatment will continue until disease progression death unacceptable toxicity or withdrawal of consent
Cohort B BRAFi MEKi rechallenge Patients with CRPR as best response to previous BRAFi MEKi combination therapy discontinuation of this therapy after progression and different therapy for 3 months prior to enrollment
These patients will receive dabrafenib and trametinib at their recommended combination therapy doses of 150 mg twice daily BID and 2 mg daily QD
Treatment will continue until disease progression death unacceptable toxicity or withdrawal of consent
Survival will be assessed every 3 months after the final dose of BRAFi MEKi until the end of the follow-up phase for the individual patient
Follow up phase for each subject is 1 year following first treatment dose End of study will be at recruitment finished plus 1 year post start of treatment of last patient thus ensuring that 1 year survival rate can be estimated
Biopsies taken before start of treatment after 2 weeks - 4 days and after progressive disease will be analyzed by Next generation sequencing NGS immunohistochemistry IHC phosphorplex Luminex as well as by reverse phase protein array in order to determine the magnitude of suppression of downstream signaling as well as reactivation of adaptative mechanisms
Rebiopsy is mandatory after 2 weeks and in case of progressive disease in order to determine mechanisms of adaptation of the signaling pathway downstream
The experimental molecular data will be analyzed in correlation with clinical response at week 8 defined as partial or complete response according to RECIST and metabolic responses at weeks 2 and 8 responders are defined as those patients with changes of 66 in the Standard Uptake value SUVmax between interim PET and baseline PET
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None