BRAF V600 Colorectal Cancer Clinical Trial
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
| Verified date | June 2024 |
| Source | Novartis |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Active, not recruiting |
| Enrollment | 122 |
| Est. completion date | October 11, 2024 |
| Est. primary completion date | October 11, 2024 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Novartis Investigative Site | Westmead | New South Wales |
| Belgium | Novartis Investigative Site | Bruxelles | |
| Belgium | Novartis Investigative Site | Leuven | |
| Canada | Novartis Investigative Site | Toronto | Ontario |
| Germany | Novartis Investigative Site | Dresden | |
| Germany | Novartis Investigative Site | Essen | |
| Germany | Novartis Investigative Site | Ulm | |
| Israel | Novartis Investigative Site | Tel Aviv | |
| Netherlands | Novartis Investigative Site | Amsterdam | |
| Singapore | Novartis Investigative Site | Singapore | |
| Spain | Novartis Investigative Site | Barcelona | Catalunya |
| Spain | Novartis Investigative Site | Madrid | |
| Spain | Novartis Investigative Site | Valencia | Comunidad Valenciana |
| United Kingdom | Novartis Investigative Site | Manchester | |
| United States | Massachusetts General Hospital Massachusetts General Hospital | Boston | Massachusetts |
| United States | Uni of TX MD Anderson Cancer Cntr | Houston | Texas |
| United States | University Of California LA Santa Monica Location | Los Angeles | California |
| United States | Sarah Cannon Research Institute SC | Nashville | Tennessee |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
United States, Australia, Belgium, Canada, Germany, Israel, Netherlands, Singapore, Spain, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Incidence and nature of dose limiting toxicities (DLTs) in the first cycle | To characterize safety and tolerability of each treatment arm tested and identify recommended doses (RD) and regimens for future studies | 30 months | |
| Primary | Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs, and ECGs | To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies | 34 months | |
| Primary | Frequency of dose interruptions | To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies | 30 months | |
| Primary | Frequency of dose reductions | To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies | 30 months | |
| Primary | Dose intensity | To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies | 30 months | |
| Secondary | AUClast derived from Serum/plasma concentration of individual investigational drugs within combination treatments | To characterize the PK of each investigational drug within each treatment arm | 30 months | |
| Secondary | Best overall response (BOR) | To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1. | 34 months | |
| Secondary | Progression free survival (PFS) | To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1. | 34 months | |
| Secondary | Overall response rate (ORR) | To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1. | 34 months | |
| Secondary | Duration of response (DOR) | To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1. | 34 months | |
| Secondary | Disease control rate (DCR) | To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1. | 34 months | |
| Secondary | Change from baseline of the PD marker DUSP6 in tumor tissue (dose escalation only) | To evaluate PD effect in their respective combinations in tumor | 30 months | |
| Secondary | AUCtau derived from Serum/plasma concentration of individual investigational drugs within combination treatments | To characterize the PK of each investigational drug within each treatment arm | 30 months | |
| Secondary | Cmax derived from Serum/plasma concentration of individual investigational drugs within combination treatments | To characterize the PK of each investigational drug within each treatment arm | 30 months | |
| Secondary | Tmax derived from Serum/plasma concentration of individual investigational drugs within combination treatments | To characterize the PK of each investigational drug within each treatment arm | 30 months |