Patient case: 62-year-old female with mucosal melanoma; genetic feature: KIT (L576P), KIT amplification

Clinical trial: Predictive Value of Progastrin Titer at Diagnosis and of Progastrin Kinetics During Treatment in Cancer Patients

Summary: Progastrin is a pro-hormone that, in physiological conditions, is maturated in gastrin in G cells of the stomach. The role of the gastrin is to stimulate the secretion of gastric acids during digestion. It is also important for the regulation of cell growth of the gastric mucosal.
  In a healthy person, progastrin is not detectable in the peripheral blood. However, progastrin is abnormally released in the blood of patients with different cancers (colorectal, gastric, ovarian, breast, cervix uterus, melanoma…) The gene GAST coding for progastrin is a direct target gene of the WNT/ß-catenin oncogenic pathway. The activation of this oncogenic pathway is an early event in cancer development.
  Chronic activation of the WNT/ß-catenin oncogenic pathway occurs in almost all human solid tumors and is a central mechanism in cancer biology that induces cellular proliferation, blocking of differentiation leading to primary tumor growth and metastasis formation.
  Progastrin measured in the peripheral blood of patients on treatments, could be a new powerful marker for diagnosis and prognosis at different stages.


Eligibility: Inclusion Criteria:
  • Histologically and/or cytologically documented, newly diagnosed cancers for the following cohorts:
  -  Breast carcinomas
  -  Gastric carcinomas
  -  Renal carcinomas
  -  Prostate carcinomas
  -  Melanoma
  -  Lung carcinomas: NSCLC and SCLC
  -  Hepatocellular carcinomas
  -  Colorectal carcinomas
  -  Head and neck carcinomas
  -  Pancreatic carcinomas
  -  Ovarian adenocarcinomas
  -  Glioblastoma
  -  Endometrial adenocarcinomas
  -  Bladder carcinoma
  -  Superficial Oesophago-gastric carcinomas
  -  Diffuse Large B-cell Lymphomas
  • Patient older than 18 years.
  • Measured creatinine clearance > 30 mL/min or creatinine ≤ 1.5 x ULN
  • Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 x ULN, unless liver metastases are present, in which case they must be ≤ 5 x ULN. For the hepatocellular carcinoma cohort, see details below
  • Serum bilirubin ≤ 1.5 x ULN. For the hepatocellular carcinoma cohort, see details below
  • Patients who gave its written informed consent to participate to the study
  • Patients affiliated to a social insurance regime
  • Specific inclusion criteria for curative treatment strategy cancer patients:
  -  Indication of a treatment strategy with curative intent (surgery; radiotherapy; chemotherapy; hormonotherapy; targeted agents…)
  • Specific inclusion criteria for non-curative treatment strategy cancer patients:
  -  Indication of a treatment strategy with no curative intent (radiotherapy; chemotherapy; hormonotherapy; immunotherapy; targeted agents …)
  The following tumor type specific inclusion criteria must be met in addition to the inclusion criteria listed above:
  Breast carcinomas
  -  Invasive breast ductal carcinoma, or
  -  Invasive breast lobular carcinoma • Curative intent treatment patient cohort:
  -  Planned to be treated with neo-adjuvant and/or adjuvant chemotherapy, surgery with/without anti-hormone treatment
  Gastric carcinomas
  -  Intestinal-type adenocarcinoma, or
  -  Diffuse cell type adenocarcinoma • Curative intent treatment patient cohort:
  -  Planned to be treated with neo-adjuvant and/or adjuvant chemotherapy, and surgery
  Renal carcinomas
  -  Any histology of renal cancer is accepted (non-clear cell renal cancer could be included)
  • Curative intent treatment patients cohort:
  -  Planned to be treated with partial or total nephrectomy
  -  A pathology proof of renal cell carcinoma is not necessary provided if patients present typical radiologic characteristics of renal cancer on imaging
  Prostate carcinomas
  -  Curative intent treatment patients cohort:
  o Localized prostate cancer with high risk features : StageT2b or T3 and/or Gleason >= 4+3 and/or PSA >= 20 and/or N+
  o Planned to be treated with radical prostatectomy or radiotherapy (potentially associated with androgen deprivation therapy). Brachytherapy and/or focused ultrasounds are not allowed.
  -  Non-curative intent treatment patients cohort:
  -  Patients with metastatic castration resistant prostate cancer (mCRPC) defined by validated criteria of EAU, planned to be treated with doceteaxel or cabazitaxel or second generation hormone (i.e. abiraterone or enzalutamide)
  Melanoma
  -  Stage I-IV melanoma, including ocular and mucosal melanoma
  • Curative intent treatment patients cohort:
  -  Planned to be treated with surgery with/without adjuvant treatment
  Lung carcinomas: NSCLC and SCLC
  -  Cytologically or histologically confirmed NSCLC (all subtypes) or SCLC. • Curative intent treatment patients cohort:
  -  NSCLC histology only
  -  Stage I-II according to 8th TNM classification
  -  Stage IIIA-B according to 8th TNM classification
  -  Histological/cytological diagnosis before curative surgery.
  -  Planned to be treated with radical treatment (surgery and/radiotherapy with/without concurrent chemotherapy), potentially associated with neo-adjuvant or adjuvant treatment • Non-curative intent patients cohort:
  -  NSCLC stage IV according to 8th TNM classification
  -  SCLC stage IV according to 8th TNM classification
  Hepatocellular carcinomas
  -  Aspartate aminotransferase / ASAT and Alanine aminotransferase / ALAT levels are accepted up to ≤ 5 x ULN
  -  Serum bilirubin ≤ 50 µM/L
  -  Absence or chronic hepatic encephalopathy, absence of refractory ascites, prothrombin rate ≥40% (or factor V ≥ 40% in case of antivitamin K therapy, albuminemia ≥ 25 g/L).
  • Curative intent treatment patients cohort:
  -  Indication of a treatment strategy with curative intent, except liver transplantation: surgical resection, monopolar radiofrequency ablation for HCC (1 to 3 nodules ≤3 cm) or multibipolar radiofrequency if nodule ≤4 cm).
  • Non-curative intent patients cohort:
  -  Indication of a treatment strategy with no curative intent: transarterial intra-hepatic chemoembolization, targeted therapies (tyrosine kinase inhibitors or monoclonal antibodies) or immune therapy.
  Colorectal carcinomas • Curative intent treatment patients cohort:
  o Lieberkühn adenocarcinoma associated with metastases planned to be treated with peri-operative chemotherapy +/- targeted agent and interval surgery
  Head and neck carcinomas
  -  Head and neck squamous cell carcinoma from oral cavity, oropharynx, hypopharynx, larynx
  • Curative intent treatment patients cohort:
  -  Planned to be treated with a radical treatment (surgery and/or radiotherapy potentially associated with concurrent chemotherapy) with/without neo-adjuvant/adjuvant chemotherapy.
  Pancreatic carcinomas • Curative intent patients cohort:
  o Pancreas exocrine adenocarcinoma planned to be treated with initial surgery followed by adjuvant chemotherapy
  Ovarian adenocarcinomas • Curative intent patients cohort:
  -  High grade epithelial adenocarcinomas
  -  No indication of primary cytoreductive surgery due to disease extend
  -  Planned to be treated with neo-adjuvant chemotherapy followed by interval debulking surgery
  Glioblastoma
  -  Curative intent patients cohort:
  -  Planned to be treated with surgical resection, followed by adjuvant temozolomide and radiotherapy
  Endometrial adenocarcinomas • Non-curative intent patients cohort:
  -  Type 1 (endometrioid or mucinous) or type 2 endometrial (serous, clear cell, undifferentiated carcinoma and carcinosarcoma) cancers
  -  Planned to be treated with non-curative systemic treatment for metastatic or advanced disease
  Bladder carcinoma
  -  Transitional cell carcinoma • Curative intent treatment patients:
  -  Patients with localized muscle invasive bladder cancer (>=PT2)
  -  Planned to be treated with neo-adjuvant cisplatin based chemotherapy (MVAC or dd-MVAC)
  Superficial Oesophago-gastric carcinomas
  -  Curative intent patients cohort:
  -  Superficial oesophago-gastric carcinomas of Stage T1 planned to be treated by endoscopic surgery
  Diffuse Large B-Cell Lymphoma (DLBCL) • Curative intent patients cohort: o Patients planned to be treated with R-CHOP (Rituximab-Cyclophosphamide, Hydroxyadriamycine, Oncovin, Prednisone)
  Exclusion Criteria:
  Specific non-inclusion criteria for curative treatment strategy cancer patients:
  -  previous therapies for cancer for ≤ 5 years.
  -  history of previous cancers, except for adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, treated and with no evidence of disease for ≥ 5 years
  Specific non-inclusion criteria for non-curative treatment strategy cancer patients:
  -  history of previous cancers for ≤ 5 years, except for relapse of the current cancer after curative-intent treatment strategy
  -  Previous therapies for cancer in metastatic setting.
  Tumor type specific non-inclusion criteria:
  Breast carcinoma:
  • non adenocarcinoma tumor
  Gastric carcinoma:
  • non adenocarcinoma tumor
  Melanoma:
  • Melanoma in situ.
  Lung carcinoma:
  -  SCLC for curative-intent cohort
  -  Stage IV NSCLC with EGFR activating mutation, BRAF V600E mutation, ALK or ROS1 fusion.
  Hepatocellular carcinoma:
  -  Fibro-lamellar hepatocellular carcinoma.
  -  Mixed cholangio-carcinoma.
  -  Patients listed for liver transplantation.
  Colorectal carcinoma:
  • non adenocarcinoma tumor
  Head and neck carcinoma:
  • Carcinoma of the nasopharynx, squamous cell carcinoma of unknown primary, squamous cell carcinoma of the skin or salivary gland, or non-squamous histology.
  Pancreatic carcinoma:
  • non adenocarcinoma tumor
  Ovarian adenocarcinoma:
  -  borderline tumors
  -  Germ cell tumors
  -  Carcinosarcoma, sex cord stromal tumors, clear-cells carcinomas
  -  Low-grade carcinomas
  Glioblastoma:
  -  Unresectable glioblastoma,
  -  Patient ineligible to post-operative temozolomide radiochemotherapy
  Endometrial adenocarcinoma:
  • Non adenocarcinoma tumor
  Superficial Oesophago-gastric carcinoma:
  • non adenocarcinoma tumor

Relevance to patient case: not relevant