Clinical trial NCT04294160: A Study of Select Drug Combinations in Adult Patients With Advanced/Metastatic BRAF V600 Colorectal Cancer
Official 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: BRAF V600 Colorectal Cancer
Keywords: Phase Ib, BRAF-mutated, BRAF V600E, BRAF V600D, BRAF V600K, colorectal cancer, colon cancer, rectal cancer, metastatic, BLRM with EWOC
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-03-03
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: This is a phase Ib, multi-center, open-label study with multiple treatment arms in adult patients with advanced or metastatic BRAF V600 (E, D, or K) in order to characterize safety and tolerability of each treatment arm tested and to identify recommended doses and regimens for future studies. The open platform design of this study is adaptive to allow removal of combination treatment arm(s) based on emerging data and facilitate introduction of new candidate combinations. The study is comprised of a dose escalation part and may be followed by a dose expansion part for any combination treatment arm.

Eligibility criteria: Key Inclusion Criteria:

* 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 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.

Primary outcomes:
measure: Incidence and nature of dose limiting toxicities (DLTs) in the first cycle
timeFrame: 30 months
measure: Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs, and ECGs
timeFrame: 34 months
measure: Frequency of dose interruptions
timeFrame: 30 months
measure: Frequency of dose reductions
timeFrame: 30 months
measure: Dose intensity
timeFrame: 30 months
Secondary outcomes:
measure: AUClast derived from Serum/plasma concentration of individual investigational drugs within combination treatments
timeFrame: 30 months
measure: Best overall response (BOR)
timeFrame: 34 months
measure: Progression free survival (PFS)
timeFrame: 34 months
measure: Overall response rate (ORR)
timeFrame: 34 months
measure: Duration of response (DOR)
timeFrame: 34 months
measure: Disease control rate (DCR)
timeFrame: 34 months
measure: Change from baseline of the PD marker DUSP6 in tumor tissue (dose escalation only)
timeFrame: 30 months
measure: AUCtau derived from Serum/plasma concentration of individual investigational drugs within combination treatments
timeFrame: 30 months
measure: Cmax derived from Serum/plasma concentration of individual investigational drugs within combination treatments
timeFrame: 30 months
measure: Tmax derived from Serum/plasma concentration of individual investigational drugs within combination treatments
timeFrame: 30 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California LA Santa Monica Location
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital Massachusetts General Hospital
state: Massachusetts
city: Nashville
country: United States
facility: Sarah Cannon Research Institute SC
state: Tennessee
city: Houston
country: United States
facility: Uni Of TX MD Anderson Cancer Cntr
state: Texas
city: Westmead
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Zoetermeer
country: Netherlands
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: