Clinical Trials /

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

NCT04294160

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: CADPT01C12101
  • NCT ID: NCT04294160

Conditions

  • BRAF V600 Colorectal Cancer

Interventions

DrugSynonymsArms
DabrafenibDRB436, TafinlarDabrafenib + LTT462 + LXH254 triplet arm 2
LTT462Dabrafenib + LTT462 + LXH254 triplet arm 2
TrametinibTMT212, MekinistDabrafenib + LTT462 + trametinib triplet arm 1
LXH254Dabrafenib + LTT462 + LXH254 triplet arm 2
TNO155Dabrafenib + LTT462 + TNO155 triplet arm 3
SpartalizumabPDR001Dabrafenib + LTT462 + spartalizumab triplet arm 4

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Dabrafenib + LTT462 backbone arm 1Experimentaldose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
  • Dabrafenib
  • LTT462
Dabrafenib + LTT462 + trametinib triplet arm 1Experimentaldose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
  • Dabrafenib
  • LTT462
  • Trametinib
Dabrafenib + LTT462 + LXH254 triplet arm 2Experimentaldose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
  • Dabrafenib
  • LTT462
  • LXH254
Dabrafenib + LTT462 + TNO155 triplet arm 3Experimentaldose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
  • Dabrafenib
  • LTT462
  • TNO155
Dabrafenib + LTT462 + spartalizumab triplet arm 4Experimentaldose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
  • Dabrafenib
  • LTT462
  • Spartalizumab
Dabrafenib + trametinib + TNO155 triplet arm 5Experimentaldose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
  • Dabrafenib
  • Trametinib
  • TNO155

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

Measure:AUClast derived from Serum/plasma concentration of individual investigational drugs within combination treatments
Time Frame:30 months
Safety Issue:
Description:To characterize the PK of each investigational drug within each treatment arm
Measure:Best overall response (BOR)
Time Frame:34 months
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
Measure:Progression free survival (PFS)
Time Frame:34 months
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
Measure:Overall response rate (ORR)
Time Frame:34 months
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
Measure:Duration of response (DOR)
Time Frame:34 months
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
Measure:Disease control rate (DCR)
Time Frame:34 months
Safety Issue:
Description:To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
Measure:Change from baseline of the PD marker DUSP6 in tumor tissue (dose escalation only)
Time Frame:30 months
Safety Issue:
Description:To evaluate PD effect in their respective combinations in tumor
Measure:AUCtau derived from Serum/plasma concentration of individual investigational drugs within combination treatments
Time Frame:30 months
Safety Issue:
Description:To characterize the PK of each investigational drug within each treatment arm
Measure:Cmax derived from Serum/plasma concentration of individual investigational drugs within combination treatments
Time Frame:30 months
Safety Issue:
Description:To characterize the PK of each investigational drug within each treatment arm
Measure:Tmax derived from Serum/plasma concentration of individual investigational drugs within combination treatments
Time Frame:30 months
Safety Issue:
Description:To characterize the PK of each investigational drug within each treatment arm

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Phase Ib, BRAF-mutated, BRAF V600E, BRAF V600D, BRAF V600K, colorectal cancer, colon cancer, rectal cancer, metastatic, BLRM with EWOC

Last Updated

February 24, 2021