araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: Study of Dabrafenib+Trametinib in the Adjuvant Treatment of Stage III BRAF V600+ Melanoma After Complete Resection to Evaluate the Impact on Pyrexia Related Outcomes

Summary: This is an open-label Phase IIIb study of dabrafenib in combination with trametinib in the adjuvant treatment of melanoma after complete resection to evaluate the impact on pyrexia related outcomes of an adapted pyrexia AE-management algorithm, as well as safety, efficacy and health-related outcomes.
  Approximately 600 subjects will be enrolled to receive dabrafenib (150 mg BID) and trametinib (2 mg once daily) combination therapy for 12 months. At enrollment, subjects will be instructed on the pyrexia management algorithm.
  This study consists of two Periods for Enrolled subjects:
  -  Treatment Period - subjects will receive up to 12 months of treatment.
  -  Follow-up Period - subjects will be followed through 24 months from their first dose date for relapse, and through end of study for overall survival. Follow-up will start once treatment is complete or is prematurely discontinued and continue through the end of the study, regardless of disease recurrence.


Eligibility: Inclusion Criteria:
  -  Completely resected histologically confirmed cutaneous melanoma stage IIIA (LN metastasis >1 mm), IIIB, IIIC, IIID [AJCC (ed 8)]
  -  V600E/K mutation positive using a validated local test
  -  Subjects presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma are eligible.
  -  Subjects who have previously had Stage III melanoma at any time are not eligible.
  -  Subjects with an unknown primary melanoma are not eligible.
  -  Recovered from definitive surgery (e.g. no uncontrolled wound infections or indwelling drains).
  -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
  Exclusion Criteria:
  -  Uveal or mucosal melanoma
  -  Evidence of metastatic disease including unresectable in-transit metastasis
  -  Received any prior adjuvant or neoadjuvant treatment, including but not limited to chemotherapy, checkpoint inhibitors, targeted therapy [e.g., BRAF and/or MEK inhibitors], biologic therapy, vaccine therapy, investigational treatment, or radiotherapy for melanoma
  -  Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers and any completely resected carcinoma in situ
  -  History or current evidence of cardiovascular risk
  -  A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy

Relevance to patient case: possibly relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: Study of the Variations of Albumin Level for Patients With Unresecable Stage IIIc or Stage IV Melanoma Treated by Anti BRAF and Anti MEK

Summary: The therapeutic arsenal of metastatic melanoma has changed considerably over the past 10 years. The treatment of metastatic melanoma is now based on immunotherapy and targeted therapies, while the place of conventional chemotherapy becomes more restricted. Targeted therapies are indicated for BRAF mutated melanomas.
  The mutation BRAF leads activation of MAP Kinases pathway and the proliferation of melanoma cell in the body . About 50% of metastatic melanoma is BRAF mutated. The most frequent mutation is the V600E. The targeted therapy by anti BRAF and anti MEK allows the double bloking of the MAP Kinases pathway. This treatment is more efficient than that of the anti BRAF alone. The association of anti BRAF and anti MEK have a global survival global rate of 41% at the 1 year, against 9% for the anti BRAF .
  In 2014, a program of extended access to the association of anti BRAF and anti MEK (dabrafenib and trametinib) started in many french hospitals (Protocol Mekinist, Novartis laboratory). Patients who were included in this program and followed in Poitiers Hospital, had frequent abnormalities of albumin level without any sign of undernutrition.
  Hypoabuminemia is a poor prognosis factor described in many cancers, including metastatic melanoma.
  The only prognostic factor in metastatic melanoma is the rate of LDH . The level of albumin and its prognostic impact have not been studied for patients with a metastatic melanoma and treated by anti BRAF and anti MEK.
  The objective of this studie was to analyze the variations of albumin level in patients with unresecable stage IIIc or stage IV melanoma treated in our Center by dabrafenib and trametinib


Eligibility: Inclusion Criteria:
  -  Age > 18 ans
  -  the patients with unresecable stage IIIc or IV melanoma with BRAF V600 E or K mutation,
  -  treated by dabrafenib and trametinib by the program of extended access (research protocol Mekinist)
  Exclusion Criteria:
  -  Age < 18 ans
  -  patients who had less than 3 months of treatment,
  -  patients for which the albumin level could not be carried out before starting treatment, and after the first month

Relevance to patient case: not relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: Dose Escalation of RMC-4630 Monotherapy in Relapsed/Refractory Solid Tumors

Summary: The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of escalating doses of RMC-4630 monotherapy in adult participants with relapsed/refractory solid tumors and to identify the recommended Phase 2 dose (RP2D).

Detailed description: This is an open-label, multicenter, Phase 1 study of oral RMC-4630 monotherapy in participants with advanced relapsed or refractory solid tumors. The study will include 2 components: 1) a Dose-Escalation Component for participants with relapsed or refractory solid tumors and 2) a Dose-Expansion Component for participants with relapsed or refractory solid tumors harboring certain specific mutations/rearrangements that result in hyperactivation of the RAS-MAPK pathway. Participants will be treated until disease progression per RECIST v1.1, unacceptable toxicity, or other criteria for withdrawal are met, whichever occurs first.

Eligibility: Inclusion Criteria:
  -  Participant (male or female) ≥18 years of age
  -  Participants who have advanced solid tumors that have failed, are intolerant to, or are considered ineligible for standard of care anticancer treatments including approved drugs for oncogenic drivers in their tumor type
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  -  Participants in the Dose-Expansion Component must have one of the following genotypic aberrations: RTK mutations, amplifications or rearrangements, KRASG12, BRAF Class 3, or NF1 LOF mutations
  -  Adequate hematologic, hepatic and renal function
  -  Participant able to understand and voluntarily sign the informed consent form (ICF) and able to comply with the study visit schedule and other protocol requirements.
  -  Participants willing to agree to not father a child/become pregnant and comply with effective contraception criteria
  Exclusion Criteria:
  -  Known or suspected leptomeningeal or brain metastases or spinal cord compression
  -  Primary central nervous system (CNS) tumors
  -  Clinically significant cardiac disease
  -  Active, clinically significant interstitial lung disease or pneumonitis
  -  History or current evidence of retinal pigment epithelial detachment (RPED), central serous retinopathy, retinal vein occlusion (RVO), or predisposing factors to RPED or RVO
  -  Known HIV infection
  -  Active/chronic hepatitis B or C infection
  -  Any other unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a participant, impact their expected survival through the end of the study participation, and/or impact their ability to comply with the protocol prior/concomitant therapy
  -  Females who are pregnant or breastfeeding

Relevance to patient case: not relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: The Study of BGB-283 in Chinese Subjects With Local Advanced or Metastatic Malignant Solid Tumor

Summary: This study will evaluate the safety, tolerability, pharmacokinetics, food effect, and preliminary antitumor activities of BGB-283 in Chinese subjects with local advanced or metastatic malignant solid tumor.


Eligibility: Inclusion Criteria:
  1. Provided written informed consent prior to enrollment.
  2. Male or female and between 18 and 75 years old.
  3. A life expectancy of more than 12 weeks.
  4. Stage I and III: Histologically or cytologically confirmed advanced or metastatic solid tumor for which no effective standard therapy is available. We simultaneously require patients with one of B-RAF, N-RAS, or K-RAS mutation positive solid tumor.
  5. In Stage II: we require advanced or metastatic melanoma with the B-RAF mutation.
  6. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
  7. Able to swallow and retain oral medication.
  8. Adequate bone marrow, liver, and renal function:
  -  Hemoglobin > 90 g/L
  -  Absolute neutrophil count ≥ 1.5x10^9/L
  -  Platelets ≥ 100 x10^9/L
  -  Total bilirubin ≤1.5 times the upper limit of normal (ULN)
  -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN for subjects with known liver metastasis)
  -  Creatinine clearance ≥ 50 mL/min (calculated by the Cockcroft Gault formula).
  Exclusion Criteria:
  1. Female subjects who are pregnant or lactating.
  2. Prior chemotherapy, radiotherapy, immunotherapy or any investigational therapies used to control cancer must have been completed at least 4 weeks or at least 5 half-lives (whichever is shorter before study drug administration, but at least 21 days)
  3. Any major surgery within 28 days prior to enrollment.
  4. Any radiotherapy for metastatic foci within 14 days prior to enrollment,
  5. Unresolved toxicity > Grade 1 (according to NCI-CTCAE, Version 4.03) from previous anti cancer therapy.
  6. History or presence of gastrointestinal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
  7. Any clinical significant active infection that need systematic treatment, including HIV positive subjects, or known Hepatitis B or C.

Relevance to patient case: possibly relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: Safety of ADU-1604 in Adults With Metastatic Melanoma

Summary: This study is a first-in-human, open-label, multicenter, dose-escalation study designed to evaluate the safety, PK, and PD of ADU-1604 and explore initial clinical activity in adults with metastatic melanoma.

Detailed description: ADU-CL-17 is a first-in-human, open-label, multicenter, dose-escalation study designed to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ADU-1604, an anti-CTLA-4 monoclonal antibody, and explore initial clinical activity in adults with metastatic melanoma. The primary objective of the study is to determine the Recommended Phase 2 Dose (RP2D) of ADU-1604 administered by IV infusion once every 3 weeks for 4 doses.
  The study will be conducted in two parts: Dose Escalation followed by Dose Confirmation.

Eligibility: Inclusion Criteria:
  1. Male or female aged ≥18 years
  2. Histologically-confirmed metastatic or unresectable melanoma
  3. Progression of disease following at least one prior therapy, and is not a candidate for, or is intolerant to, established therapy known to provide clinical benefit (i.e. available treatment options have been exhausted). Subjects must have BRAF mutation status confirmed; if a subject is BRAF V600E/K positive, they must have received a BRAF- targeted regimen prior to entering the study, unless the patient was deemed ineligible for such treatment
  4. Measurable disease according to RECIST (v1.1) [NOT required during Dose Escalation]
  5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  Exclusion Criteria:
  1. Prior diagnosis of uveal or mucosal melanoma
  2. Prior treatment with CTLA-4-directed therapy in the metastatic setting. Use of CTLA- 4-directed treatment in the adjuvant or neoadjuvant setting is acceptable provided the last dose was >6 months before the first dose of ADU-1604 and there was no discontinuation of treatment due to a treatment-related toxicity.

Relevance to patient case: possibly relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: A Study is to Understand the Treatment Patterns for Immunotherapy Agents and BRAF/MEK Inhibitors Used in the Treatment of Advanced Melanoma

Summary: The goal of the study is to understand the treatment patterns for immunotherapy agents and BRAF/MEK inhibitors used in the treatment of advanced melanoma


Eligibility: Inclusion Criteria:
  -  Patients must have ≥1 medical or pharmacy claim for nivolumab, ipilimumab, pembrolizumab, nivolumab+ipilimumab (on the same day), dabrafenib, vemurafenib, cobimetinib, trametinib, dabrafenib+trametinib (on the same day) and vemurafenib+cobimetinib (on the same day)
  -  Patients must have ≥6 months of continuous health plan enrollment prior to index date
  -  Patients must have ≥2 medical claims at least 30 days apart with a diagnosis for melanoma during the study period AND ≥1 diagnosis for melanoma during the baseline period prior to or on the index date
  Exclusion Criteria:
  -  Patients with ≥1 claim for the agents of interest including immunotherapy agents and BRAF/MEK inhibitors between the first diagnosis of metastatic disease and the day prior to the index date will be excluded
  -  Patients with a claim for acquired immunodeficiency virus (AIDS) anytime during the study period
  -  Patients under the age of 18 as of index date
  Other protocol defined inclusion/exclusion criteria could apply

Relevance to patient case: not relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: Preclinical Validation of New Anti-melanoma Compounds

Summary: This research program is in keeping with the chemistry/biology/clinical interface and gathers 4 teams with complementary expertise in these respective fields. It will allow deciphering the mechanism(s) of action of new Thiazole-Benzenesulfonamide family (TZB) derivatives on metastatic melanoma sensitive and resistant to BRAF and MEK inhibitors. Investigators will use melanoma cell lines and primary cells from patients to validate these compounds in collaboration with clinical team 2 and 4. In conclusion, the investigators expect to establish the proof of concept that this new class of bioactive molecules (first in class) we developed in collaboration with Team 3 have the potential to go to the clinic for the treatment of highly aggressive cancers and particularly metastatic melanoma sensitive and resistant B-Raf and MEK inhibitors. Furthermore, the realization of this project can undoubtedly increase the knowledge of mechanisms and signaling pathways that are involved in resistant to BRAF and MEK inhibitors, and allow the selection of drug candidates capable of restoring the sensitivity of these melanoma cells.


Eligibility: Inclusion Criteria:
  -  Patient with metastatic melanoma
  -  Not opposition of the patient will have been looked for
  Exclusion Criteria:
  -  Primary resistance,
  -  Absence of resistance,
  -  Patient already included in other trials

Relevance to patient case: not relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: An Open-Label, Randomized, Multicenter Trial of Encorafenib + Binimetinib Evaluating a Standard-dose and a High-dose Regimen in Patients With BRAFV600-mutant Melanoma Brain Metastasis

Summary: This is a multicenter, randomized open-label Phase 2 study to assess the safety, efficacy and pharmacokinetic (PK) of 2 dosing regimens of encorafenib + binimetinib combination in patients with BRAFV600-mutant melanoma with brain metastasis. Approximately 100 patients will be enrolled, including 9 patients in a Safety Lead-in of the high-dose treatment arm. After a Screening Period, treatment will be administered in 28-day cycles and will continue until disease progression, unacceptable toxicity, withdrawal of consent, start of subsequent anticancer therapy, death.


Eligibility: Key Inclusion Criteria:
  -  Histologically confirmed diagnosis of melanoma.
  -  Presence of B-RAF proto-oncogene, V600 mutant (BRAFV600) mutation in tumor tissue previously determined by a local assay at any time prior to Screening or by a central laboratory during Screening.
  -  Metastatic disease to the brain with at least 1 parenchymal brain lesion ≥ 0.5 cm and ≤ 4 cm, defined as a magnetic resonance imaging (MRI) contrast-enhancing lesion that may be accurately measured in at least 1 dimension.
  -  Patients may have received no more than 1 prior line of checkpoint inhibitor therapy.
  -  An Eastern Cooperation Oncology Group Performance Status (ECOG PS) of 0 or 1 and Karnofsky score ≥ 80
  -  Adequate bone marrow, organ function and laboratory parameters
  Key Exclusion Criteria:
  -  Patients with symptomatic brain metastasis.
  -  Patients requiring corticosteroids for brain metastasis.
  -  Uveal or mucosal melanoma.
  -  History of or current leptomeningeal metastases.
  -  Prior local treatment for brain metastasis, including whole brain radiation therapy, stereotactic radiosurgery or craniotomy.
  -  Either of the following:
  1. Radiation therapy to non-brain visceral metastasis within 2 weeks prior to start of study treatment;
  2. Continuous or intermittent small-molecule therapeutics or investigational agents within 5 half-lives of the agent (or within 4 weeks prior to start of study treatment, when half-life is unknown).
  -  Patients treated in the adjuvant setting with BRAF or MEK inhibitor(s) < 12 months prior to enrollment. Patients treated in the adjuvant setting with B-RAF proto-oncogene, serine/threonine kinase (BRAF) or mitogen-activated protein kinase (MEK) inhibitors ≥ 12 months prior to enrollment are eligible. Patients who received BRAF or MEK inhibitors in the metastatic setting are excluded.
  -  Patient has not recovered to ≤ Grade 1 from toxic effects of prior therapy before starting study treatment.

Relevance to patient case: possibly relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: Folfirinox + Cetuximab Chemotherapy, in First Line, With Wild RAS and According to BRAF Status in Metastatic Colorectal Cancer

Summary: This retrospective study, will evaluate patient outcomes after triplet chemotherapy (FOLFIRINOX) (5 Fluorouracil + oxaliplatin + irinotecan) plus cetuximab 1st line treatment focusing on efficacy and safety in a RAS (KRAS, NRAS (neuroblastoma rat sarcoma viral oncogene homolog) wild-type metastatic colorectal cancer population, and according to BRAF (murine sarcoma viral oncogene homolog B) status and primary tumor location.

Detailed description: In Europe, there are 447,000 new cases of colorectal cancer each year. Approximately 25% of patients present with metastases at initial diagnosis and almost 50% of patients with mCRC (metastatic colorectal cancer) will develop metastases
  . Chemotherapy represents the backbone of treatment, and survival is linked with the administration of all three active cytotoxic agents (5-fluorouracil/folinate, oxaliplatin, and irinotecan) in the first line treatment of metastatic colorectal disease.
  Monoclonal antibodies such as cetuximab in combination with chemotherapy are a first line treatment option in metastatic RAS (rat sarcoma viral oncogene homolog) wild type metastatic colorectal cancer (mCRC).
  Phase II trials evaluating triplet chemotherapy plus cetuximab reported interesting results in terms of efficacy (response rate, resectability...), but at the price of an increased rate of toxic effects.
  This retrospective study, will evaluate patient outcomes after triplet chemotherapy (FOLFIRINOX) (5 Fluorouracil + oxaliplatin + irinotecan) plus cetuximab 1st line treatment focusing on efficacy and safety in a RAS (KRAS, NRAS (neuroblastoma rat sarcoma viral oncogene homolog) wild-type mCRC (metastatic colorectal cancer) population, and according to BRAF (murine sarcoma viral oncogene homolog B) status and primary tumor location.

Eligibility: Inclusion Criteria:
  1. Colorectal cancer confirmed as RAS wild by tumor tissue analysis
  2. Non resectable and measurable metastatic disease
  3. Patients treated with FOLFIRINOX + cetuximab in first line metastatic disease
  4. Males or females aged over 18 years.
  Exclusion Criteria:
  1. Known brain metastases
  2. RAS not assessable (e.g., material not available or insufficient)
  3. The first administration of cetuximab was more than 30 days after the first administration of FOLFIRINOX
  4. History of other malignancy in the last 5 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Patients with other malignancies are eligible if they were cured by surgery alone or surgery plus radiotherapy and have been continuously disease-free for at least 5 years

Relevance to patient case: not relevant