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JOURNAL ONKOLOGIE – STUDIE

A Study of Select Drug Combinations in Adult Patients With Advanced/Metastatic BRAF V600 Colorectal Cancer

Rekrutierend

NCT-Nummer:
NCT04294160

Studienbeginn:
Juli 2020

Letztes Update:
28.04.2021

Wirkstoff:
Dabrafenib, LTT462, Trametinib, LXH254, TNO155, Spartalizumab

Indikation (Clinical Trials):
Colorectal Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Novartis Pharmaceuticals

Collaborator:
-

Kontakt

Studienlocations
(3 von 17)

Novartis Investigative Site
01307 Dresden
(Sachsen)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
45147 Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
89081 Ulm
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
University of California at Los Angeles Santa Monica Location
90095 Los Angeles
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Sandy Hernandez
Phone: 310-582-4069
E-Mail: SCHernandez@mednet.ucla.edu
» Ansprechpartner anzeigen
Novartis Investigative Site
2145 Westmead
AustraliaRekrutierend» Google-Maps
Novartis Investigative Site
1000 Bruxelles
BelgiumRekrutierend» Google-Maps
Novartis Investigative Site
M5G 1Z5 Toronto
CanadaRekrutierend» Google-Maps
Novartis Investigative Site
6423906 Tel Aviv
IsraelRekrutierend» Google-Maps
Novartis Investigative Site
1066 CX Amsterdam
NetherlandsRekrutierend» Google-Maps
Novartis Investigative Site
119228 Singapore
SingaporeRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

1. Incidence and nature of dose limiting toxicities (DLTs) in the first cycle (Time Frame - 30 months):
To characterize safety and tolerability of each treatment arm tested and identify recommended doses (RD) and regimens for future studies

2. Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs, and ECGs (Time Frame - 34 months):
To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies

3. Frequency of dose interruptions (Time Frame - 30 months):
To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies

4. Frequency of dose reductions (Time Frame - 30 months):
To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies

5. Dose intensity (Time Frame - 30 months):
To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies

Secondary outcome:

1. AUClast derived from Serum/plasma concentration of individual investigational drugs within combination treatments (Time Frame - 30 months):
To characterize the PK of each investigational drug within each treatment arm

2. Best overall response (BOR) (Time Frame - 34 months):
To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.

3. Progression free survival (PFS) (Time Frame - 34 months):
To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.

4. Overall response rate (ORR) (Time Frame - 34 months):
To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.

5. Duration of response (DOR) (Time Frame - 34 months):
To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.

6. Disease control rate (DCR) (Time Frame - 34 months):
To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.

7. Change from baseline of the PD marker DUSP6 in tumor tissue (dose escalation only) (Time Frame - 30 months):
To evaluate PD effect in their respective combinations in tumor

8. AUCtau derived from Serum/plasma concentration of individual investigational drugs within combination treatments (Time Frame - 30 months):
To characterize the PK of each investigational drug within each treatment arm

9. Cmax derived from Serum/plasma concentration of individual investigational drugs within combination treatments (Time Frame - 30 months):
To characterize the PK of each investigational drug within each treatment arm

10. Tmax derived from Serum/plasma concentration of individual investigational drugs within combination treatments (Time Frame - 30 months):
To characterize the PK of each investigational drug within each treatment arm

Studien-Arme

  • 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
  • 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
  • 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

Geprüfte Regime

  • Dabrafenib (DRB436, Tafinlar):
    Capsule for oral use
  • LTT462:
    Capsule for oral use
  • Trametinib (TMT212, Mekinist):
    Tablet for oral use
  • LXH254:
    Tablet for oral use
  • TNO155:
    Capsule for oral use
  • Spartalizumab (PDR001):
    Liquid in vial (Concentrate for solution for infusion) for intravenous use

Quelle: ClinicalTrials.gov


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