Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT04294160
Registration number
NCT04294160
Ethics application status
Date submitted
2/03/2020
Date registered
3/03/2020
Date last updated
11/06/2024
Titles & IDs
Public title
A Study of Select Drug Combinations in Adult Patients With Advanced/Metastatic BRAF V600 Colorectal Cancer
Query!
Scientific title
A Phase Ib, Multicenter, Open-label Dose Escalation and Expansion Platform Study of Select Drug Combinations in Adult Patients With Advanced or Metastatic BRAF V600 Colorectal Cancer
Query!
Secondary ID [1]
0
0
CADPT01C12101
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
BRAF V600 Colorectal Cancer
0
0
Query!
Condition category
Condition code
Cancer
0
0
0
0
Query!
Bowel - Back passage (rectum) or large bowel (colon)
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Drugs - Dabrafenib
Treatment: Drugs - LTT462
Treatment: Drugs - Trametinib
Treatment: Drugs - LXH254
Treatment: Drugs - TNO155
Treatment: Other - Spartalizumab
Treatment: Other - Tislelizumab
Experimental: Dabrafenib + LTT462 backbone arm 1 - dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
Experimental: Dabrafenib + LTT462 + trametinib triplet arm 1 - dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
Experimental: Dabrafenib + LTT462 + LXH254 triplet arm 2 - dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer - Arm is closed for further enrollment.
Experimental: Dabrafenib + LTT462 + TNO155 triplet arm 3 - dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
Experimental: Dabrafenib + LTT462 + spartalizumab triplet arm 4 - dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer - Arm is closed for further enrollment.
Experimental: Dabrafenib + trametinib + TNO155 triplet arm 5 - dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
Experimental: Dabrafenib + LTT462 + Tislelizumab triplet arm 6 - dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
Treatment: Drugs: Dabrafenib
Capsule for oral use
Treatment: Drugs: LTT462
Capsule for oral use
Treatment: Drugs: Trametinib
Tablet for oral use
Treatment: Drugs: LXH254
Tablet for oral use
Treatment: Drugs: TNO155
Capsule for oral use
Treatment: Other: Spartalizumab
Liquid in vial (Concentrate for solution for infusion) for intravenous use
Treatment: Other: Tislelizumab
Liquid in vial (Concentrate for solution for infusion) for intravenous use
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Intervention code [2]
0
0
Treatment: Other
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Incidence and nature of dose limiting toxicities (DLTs) in the first cycle
Query!
Assessment method [1]
0
0
To characterize safety and tolerability of each treatment arm tested and identify recommended doses (RD) and regimens for future studies
Query!
Timepoint [1]
0
0
30 months
Query!
Primary outcome [2]
0
0
Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs, and ECGs
Query!
Assessment method [2]
0
0
To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies
Query!
Timepoint [2]
0
0
34 months
Query!
Primary outcome [3]
0
0
Frequency of dose interruptions
Query!
Assessment method [3]
0
0
To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies
Query!
Timepoint [3]
0
0
30 months
Query!
Primary outcome [4]
0
0
Frequency of dose reductions
Query!
Assessment method [4]
0
0
To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies
Query!
Timepoint [4]
0
0
30 months
Query!
Primary outcome [5]
0
0
Dose intensity
Query!
Assessment method [5]
0
0
To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies
Query!
Timepoint [5]
0
0
30 months
Query!
Secondary outcome [1]
0
0
AUClast derived from Serum/plasma concentration of individual investigational drugs within combination treatments
Query!
Assessment method [1]
0
0
To characterize the PK of each investigational drug within each treatment arm
Query!
Timepoint [1]
0
0
30 months
Query!
Secondary outcome [2]
0
0
Best overall response (BOR)
Query!
Assessment method [2]
0
0
To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
Query!
Timepoint [2]
0
0
34 months
Query!
Secondary outcome [3]
0
0
Progression free survival (PFS)
Query!
Assessment method [3]
0
0
To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
Query!
Timepoint [3]
0
0
34 months
Query!
Secondary outcome [4]
0
0
Overall response rate (ORR)
Query!
Assessment method [4]
0
0
To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
Query!
Timepoint [4]
0
0
34 months
Query!
Secondary outcome [5]
0
0
Duration of response (DOR)
Query!
Assessment method [5]
0
0
To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
Query!
Timepoint [5]
0
0
34 months
Query!
Secondary outcome [6]
0
0
Disease control rate (DCR)
Query!
Assessment method [6]
0
0
To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
Query!
Timepoint [6]
0
0
34 months
Query!
Secondary outcome [7]
0
0
Change from baseline of the PD marker DUSP6 in tumor tissue (dose escalation only)
Query!
Assessment method [7]
0
0
To evaluate PD effect in their respective combinations in tumor
Query!
Timepoint [7]
0
0
30 months
Query!
Secondary outcome [8]
0
0
AUCtau derived from Serum/plasma concentration of individual investigational drugs within combination treatments
Query!
Assessment method [8]
0
0
To characterize the PK of each investigational drug within each treatment arm
Query!
Timepoint [8]
0
0
30 months
Query!
Secondary outcome [9]
0
0
Cmax derived from Serum/plasma concentration of individual investigational drugs within combination treatments
Query!
Assessment method [9]
0
0
To characterize the PK of each investigational drug within each treatment arm
Query!
Timepoint [9]
0
0
30 months
Query!
Secondary outcome [10]
0
0
Tmax derived from Serum/plasma concentration of individual investigational drugs within combination treatments
Query!
Assessment method [10]
0
0
To characterize the PK of each investigational drug within each treatment arm
Query!
Timepoint [10]
0
0
30 months
Query!
Eligibility
Key inclusion criteria
Key
* Patients must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Patients must be willing to undergo a new tumor biopsy at baseline and during on study therapy. Exceptions may be considered after documented discussion with Novartis.
* All patients must have a BRAF V600 mutation confirmed by local assessment.
* Patients with unresectable advanced/metastatic BRAF V600 cancer of the colon or rectum with measurable disease as determined by RECIST v1.1
* Patients must have documented disease progression following, or are intolerant to, 1 or 2 lines of chemotherapy for advanced/metastatic disease
Key
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
* Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in-situ cervical cancer, or other tumors that will not affect life expectancy
* Impairment of gastrointestinal function or gastrointestinal disease that may signficantly alter the absorption of study drugs
* History of or current evidence/risk of retinal verin occlusion or serous retinopathy
* History of or current interstitial lung disease or non-infectious pneumonitis
* Patients with a known history of testing positive for HIV
* Clinically significant cardiac disease at screening
* Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
* Pregnant or lactating women
Other protocol-defined inclusion/exclusion may apply.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Non-randomised trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 1
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Active, not recruiting
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
22/07/2020
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
11/10/2024
Query!
Actual
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
122
Query!
Recruitment in Australia
Recruitment state(s)
NSW
Query!
Recruitment hospital [1]
0
0
Novartis Investigative Site - Westmead
Query!
Recruitment postcode(s) [1]
0
0
2145 - Westmead
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
California
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Massachusetts
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Tennessee
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Texas
Query!
Country [5]
0
0
Belgium
Query!
State/province [5]
0
0
Bruxelles
Query!
Country [6]
0
0
Belgium
Query!
State/province [6]
0
0
Leuven
Query!
Country [7]
0
0
Canada
Query!
State/province [7]
0
0
Ontario
Query!
Country [8]
0
0
Germany
Query!
State/province [8]
0
0
Dresden
Query!
Country [9]
0
0
Germany
Query!
State/province [9]
0
0
Essen
Query!
Country [10]
0
0
Germany
Query!
State/province [10]
0
0
Ulm
Query!
Country [11]
0
0
Israel
Query!
State/province [11]
0
0
Tel Aviv
Query!
Country [12]
0
0
Netherlands
Query!
State/province [12]
0
0
Amsterdam
Query!
Country [13]
0
0
Singapore
Query!
State/province [13]
0
0
Singapore
Query!
Country [14]
0
0
Spain
Query!
State/province [14]
0
0
Catalunya
Query!
Country [15]
0
0
Spain
Query!
State/province [15]
0
0
Comunidad Valenciana
Query!
Country [16]
0
0
Spain
Query!
State/province [16]
0
0
Madrid
Query!
Country [17]
0
0
United Kingdom
Query!
State/province [17]
0
0
Manchester
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Query!
Name
Novartis Pharmaceuticals
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
A phase Ib, open-label platform study of select drug combinations chosen in order to characterize safety and tolerability of each treatment arm tested and to identify recommended doses and regimens for future studies.
Query!
Trial website
https://clinicaltrials.gov/study/NCT04294160
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Novartis Pharmaceuticals
Query!
Address
0
0
Novartis Pharmaceuticals
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/study/NCT04294160
Download to PDF