Dabrafenib + Trametinib
Switch to N+I at first progression

Dabrafenib + Trametinib
Switch to N+I when ctDNA levels in the blood have dropped by ≥80%.

Melanoma

Regular ctDNA analysis, which upon a decrease in mutant BRAF VAF (variant allele frequency) level of ≥80% the switch to N+I is triggered.

ctDNA analysis

The Christie NHS Foundation Trust

CAcTUS - Circulating Tumour DNA Guided Switch

A Parallel Arm, Biomarker Driven, Phase II Trial to Determine the Role of Circulating Tumour DNA in Guiding a Switch Between Targeted Therapy and Immune Therapy in Patients With Advanced Cutaneous Melanoma

Feasibility of returning samples to hospitals from the laboratory to inform clinical decisions

To assess whether a decrease in ctDNA levels of mutant BRAF by ≥80% on targeted therapy is an appropriate cut off for switching to immune therapy

To assess whether BRAF VAF (within the ctDNA) of ≥5% is an appropriate target for study inclusion (by assessing the number and proportion of screen failures

To explore whether PFS at 12 months would improve in patients switching from targeted to immune therapy on response to treatment as guided by ctDNA levels of mutant BRAF VAF

Explore whether survival outcomes would improve in patients switching from targeted to immune therapy on response to treatment as guided by ctDNA levels of mutant BRAF VAF

Time to first progression measured by ctDNA

Time to second progression measured by ctDNA

To explore the relationship between observing a rise in ctDNA level of mutant BRAF VAF and progressive disease observed from scheduled scan results

To compare duration in ctDNA level of mutant BRAF VAF response to targeted therapy between study arms

To compare duration in ctDNA level of mutant BRAF VAF (within ctDNA) response to immune therapy between study arms

To explore whether switching from targeted to immune therapy on treatment response as guided by ctDNA levels of mutant BRAF VAF will increase response to therapy

Dr Paul Lorigan

Chief Investigator

Bristol-Myers Squibb

University of Manchester

Manchester Academic Health Science Centre

Intractable Pain

Palliative Care

phase I, single-site, non-randomized, open-label, dose- escalation study to determine the safety and efficacy of IT RTX in subjects with severe refractory pain due to advanced malignancy

Intrathecal Resiniferatoxin

National Institutes of Health Clinical Center, 9000 Rockville Pike

Resiniferatoxin to Treat Severe Pain Associated With Advanced Cancer

A Phase I Study of the Intrathecal Administration of Resiniferatoxin for Treating Severe Refractory Pain Associated With Advanced Cancer

Dose escalation decisions are based on both effectiveness (as assessed by mean worst pain on the NRS) and DLT. The dose escalation population will include all subjects who are dosed, complete the NRS, and have the DLT assessments from baseline through Day 15. Subjects who are not evaluable for dose escalation will be replaced.

The secondary outcome variables will be summarized over time by dose cohort as appropriate for the outcome measure. Absolute and percentage change in the NRS and VAS pain scores between the pre- and post-RTX dosing assessments (baseline period and study Days 8 through 14, respectively) will also be summarized.

National Institute of Dental and Craniofacial Research (NIDCR)

National Institute of Neurological Disorders and Stroke (NINDS)

Sorrento Therapeutics, Inc.

The Low-Dose-1st Group received the low dose of psilocybin on the first session and the high dose on the second session

The High-Dose-1st Group received the high dose of psilocybin on the first session and the low dose on the second session

The Low-Dose-1st Group received the low dose of psilocybin on the first session and the high dose on the second session.

Low-Dose First

The High-Dose-1st Group received the high dose on the first session and the low dose on the second session.

High-Dose First

Total

Sex: Female, Male

Race (NIH/OMB)

Education

The GRID-Hamilton Depression Rating Scale is a 17-item clinician-administered rating scale designed to assess severity of depressive symptoms. The score range for the GRID-HAMD is 0 to 52, with higher score indicating more severe depression. For this clinician-rated measure, a clinically significant response was defined as ⩾50% decrease in measure relative to Baseline; symptom remission was defined as ⩾50% decrease in measure relative to Baseline and a score of ⩽7 on the GRID-HAMD

Low-Dose First Baseline

Low-Dose First Post Session 1

Low-Dose First Post Session 2

Low-Dose First 6 Month

High-Dose First Baseline

High-Dose First Post Session 1

High-Dose First Post Session 2

High-Dose First 6 Month

GRID-HAM-D-17 -- Structured Interview Guide for the Hamilton Depression Scale.

The Hamilton Anxiety Rating Scale is a 14-item clinician-administered rating scale designed to assess severity of anxiety symptoms. The score range for the HAM-A is 0 to 56, with higher score indicating more severe anxiety.
For this clinician-rated measure, a clinically significant response was defined as ⩾50% decrease in measure relative to Baseline; symptom remission was defined as ⩾50% decrease in measure relative to Baseline and a score of ⩽7 on the GRID-HAM-A

HAM-A Assessed With the SIGH-A -- a Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A).

Overall Study

Roland R. Griffiths, Ph.D., Principal Investigator

The experimental design of this study is a complete cross-over, with two groups of participants receiving the low and high doses of psilocybin in counterbalance order. The Low Dose Group is comprised of all low dose psilocybin sessions (n=50). The number of sessions is different from the total enrollment because of dropouts.

Low Dose Condition (Group)

The experimental design of this study is a complete cross-over, with two groups of participants receiving the low and high doses of psilocybin in counterbalance order. The High Dose Group is comprised of all high dose psilocybin sessions (n=50). The number of sessions is different from the total enrollment because of dropouts.

High Dose Condition (Group)

Depressive Symptoms

Anxiety

Cancer

The dose of psilocybin received in the two sessions will range anywhere from low to high.

ariocarpus kotschoubeyanus/rak

CAcTUS - Circulating Tumour DNA Guided Switch

Resiniferatoxin to Treat Severe Pain Associated With Advanced Cancer

Psychopharmacology of Psilocybin in Cancer Patients

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