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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

Titles & IDs
Public title
A Study of Select Drug Combinations in Adult Patients With Advanced/Metastatic BRAF V600 Colorectal Cancer
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
Secondary ID [1] 0 0
CADPT01C12101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
BRAF V600 Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
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

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence and nature of dose limiting toxicities (DLTs) in the first cycle
Timepoint [1] 0 0
30 months
Primary outcome [2] 0 0
Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs, and ECGs
Timepoint [2] 0 0
34 months
Primary outcome [3] 0 0
Frequency of dose interruptions
Timepoint [3] 0 0
30 months
Primary outcome [4] 0 0
Frequency of dose reductions
Timepoint [4] 0 0
30 months
Primary outcome [5] 0 0
Dose intensity
Timepoint [5] 0 0
30 months
Secondary outcome [1] 0 0
AUClast derived from Serum/plasma concentration of individual investigational drugs within combination treatments
Timepoint [1] 0 0
30 months
Secondary outcome [2] 0 0
Best overall response (BOR)
Timepoint [2] 0 0
34 months
Secondary outcome [3] 0 0
Progression free survival (PFS)
Timepoint [3] 0 0
34 months
Secondary outcome [4] 0 0
Overall response rate (ORR)
Timepoint [4] 0 0
34 months
Secondary outcome [5] 0 0
Duration of response (DOR)
Timepoint [5] 0 0
34 months
Secondary outcome [6] 0 0
Disease control rate (DCR)
Timepoint [6] 0 0
34 months
Secondary outcome [7] 0 0
Change from baseline of the PD marker DUSP6 in tumor tissue (dose escalation only)
Timepoint [7] 0 0
30 months
Secondary outcome [8] 0 0
AUCtau derived from Serum/plasma concentration of individual investigational drugs within combination treatments
Timepoint [8] 0 0
30 months
Secondary outcome [9] 0 0
Cmax derived from Serum/plasma concentration of individual investigational drugs within combination treatments
Timepoint [9] 0 0
30 months
Secondary outcome [10] 0 0
Tmax derived from Serum/plasma concentration of individual investigational drugs within combination treatments
Timepoint [10] 0 0
30 months

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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Novartis Investigative Site - Westmead
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
Tennessee
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
Belgium
State/province [5] 0 0
Bruxelles
Country [6] 0 0
Belgium
State/province [6] 0 0
Leuven
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
Germany
State/province [8] 0 0
Dresden
Country [9] 0 0
Germany
State/province [9] 0 0
Essen
Country [10] 0 0
Germany
State/province [10] 0 0
Ulm
Country [11] 0 0
Israel
State/province [11] 0 0
Tel Aviv
Country [12] 0 0
Netherlands
State/province [12] 0 0
Amsterdam
Country [13] 0 0
Singapore
State/province [13] 0 0
Singapore
Country [14] 0 0
Spain
State/province [14] 0 0
Catalunya
Country [15] 0 0
Spain
State/province [15] 0 0
Comunidad Valenciana
Country [16] 0 0
Spain
State/province [16] 0 0
Madrid
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.