Melanoma and Metastatic Colorectal Cancer Clinical Trial
Official title:
A Phase I, Multicenter, Open-label, Dose-escalation Study of Oral LGX818 in Adult Patients With Locally Advanced or Metastatic BRAF Mutant Melanoma
| Verified date | August 2023 |
| Source | Pfizer |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
CLGX818X2101 is a first-time in-human, phase I study to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of daily administered LGX818 (daily, twice daily and/or every-other-day), a RAF kinase inhibitor. Patients with locally advanced or metastatic melanoma harboring the BRAF V600 mutation (during dose escalation phase and expansion phase) and patients with metastatic colorectal cancer harboring the BRAF V600 mutation (during the expansion phase) will be enrolled. The study consists of a dose escalation part were cohorts of patients will receive escalating oral doses of LGX818, followed by a safety dose expansion part were patients will be treated with oral dose of LGX818 given at the MTD or RP2D.
| Status | Completed |
| Enrollment | 93 |
| Est. completion date | November 7, 2022 |
| Est. primary completion date | October 1, 2012 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: For the dose escalation phase: 1. Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]). For the dose expansion phase: (i) Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]), or (ii) confirmed diagnosis and non-resectable advanced metastatic colorectal cancer (mCRC) for which no further effective standard therapy exists. 2. Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation. 3. Evidence of measurable disease Exclusion Criteria: 1. Previous therapy with a MEK inhibitor. 2. Symptomatic or untreated leptomeningeal disease. 3. Symptomatic or untreated brain metastasis.Patients previously treated for these conditions that are asymptomatic in the absence of corticosteroid therapy are allowed to enroll. Brain metastasis must be stable with verification by imaging. 4. Known acute or chronic pancreatitis. 5. Clinically significant cardiac disease 6. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LGX818 7. Previous or concurrent malignancy. Exceptions to this exclusion criteria include: adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the cervix, treated curatively and without evidence of recurrence for at least 3 years prior to study entry; or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry. 8. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL). 9. History of thromboembolic or cerebrovascular events within the last 6 months Other protocol-defined inclusion/exclusion criteria may apply |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Peter MacCallum Cancer Centre | East Melbourne | Victoria |
| Australia | Western Sydney Local Health District | Westmead | New South Wales |
| Australia | Westmead Hospital- Redbank Rd | Westmead | New South Wales |
| France | EDOG - Institut Claudia Regaud - PPDS | Toulouse | Haute-garonne |
| France | EDOG - Institut Claudius Regaud - PPDS | Toulouse | Haute-garonne |
| France | Institut Gustave Roussy | Villejuif | ILE DE France - VAL DE Marne (94) |
| France | Institut Gustave Roussy | Villejuif | VAL DE Marne |
| France | Institut Gustave Roussy | Villejuif | Val-de-marne |
| France | Institut Gustave Roussy | Villejuif | |
| France | Institut Gustave Roussy | Villejuif Cedex | Val-de-marne |
| Japan | National Cancer Center Hospital | Chuo-ku | Tokyo |
| Norway | Oslo Myeloma Center - PPDS | Oslo | |
| Spain | Hospital Clinic de Barcelona | Badalona | |
| Spain | Hospital General Vall d'Hebron | Barcelona | |
| Spain | Hospital Universitario Vall d'Hebron | Barcelona | |
| Spain | Hospital Universitario Vall d'Hebron - PPDS | Barcelona | |
| Spain | Hospital Universitario Vall d'Hebron - PPDS | Barcelona | |
| Spain | Hospital Universitario HM Sanchinarro_CIOCC | Madrid | |
| Spain | START MADRID_Hospital Universitario HM Sanchinarro - CIOCC | Madrid | |
| Switzerland | Kantonsspital Graubünden | Chur | Graubünden (DE) |
| United States | Beth Israel Deaconess Medical Center | Boston | Massachusetts |
| United States | Brigham and Women's Hospital | Boston | Massachusetts |
| United States | Dana-Farber Cancer Institute | Boston | Massachusetts |
| United States | Massachusetts General Hospital | Boston | Massachusetts |
| United States | H Lee Moffitt Cancer Center and Research Institute | Tampa | Florida |
| Lead Sponsor | Collaborator |
|---|---|
| Pfizer |
United States, Australia, France, Japan, Norway, Spain, Switzerland,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Incidence of Dose Limiting Toxicities | Approximately every 8 weeks (up to 2 years) | ||
| Secondary | Number and nature of Adverse events and clinical activity | Approximately 3 years | ||
| Secondary | Pharmacokinetic profile of LGX818 | LGX818 Plasma concentration | Approximately 2 years | |
| Secondary | Tumor response per RECIST | This includes duration of response, time to response, progression free survival and overall survival. | Approximately 3 years | |
| Secondary | Baseline molecular status | Baseline molecular status (mutation/ amplification/ expression) in tumor tissue of potential predictive markers | Approximately 3 years |