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Predictive Value of Progastrin Titer at Diagnosis and of Progastrin Kinetics During Treatment in Cancer Patients (ONCOPRO)

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ClinicalTrials.gov Identifier: NCT03787056
Recruitment Status : Recruiting
First Posted : December 25, 2018
Last Update Posted : December 25, 2018
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

Brief 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.


Condition or disease Intervention/treatment Phase
Cancer Breast Cancer Gastric Cancer Renal Cancer Prostate Cancer Melanoma Lung Cancer Hepatocellular Cancer Colorectal Cancer Head and Neck Cancer Pancreatic Cancer Ovarian Cancer Glioblastoma Endometrial Cancer Bladder Cancer Esophageal Cancer B-cell Lymphoma Other: Blood draws Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 410 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Predictive Value of Progastrin Titer at Diagnosis and of Progastrin Kinetics During Treatment in Cancer Patients
Actual Study Start Date : December 4, 2018
Estimated Primary Completion Date : November 2026
Estimated Study Completion Date : November 2026


Arm Intervention/treatment
Cancer patients
ONCOPRO will enroll 410 patients affected by different types of cancer and treated in a curative or a palliative intent. In total 16 cohorts will be open, including: breast cancer, gastric carcinoma, renal cell carcinoma, prostate carcinoma, melanoma, lung carcinoma, hepatocellular carcinoma, colorectal carcinoma, head and neck carcinoma, pancreatic adenocarcinoma, ovarian carcinoma, glioblastoma, endometrial adenocarcinoma, bladder carcinoma, oesophago-gastric carcinoma and B-cell lymphoma. Patients enrolled in curative intent treatment cohorts will never have been previously treated for their cancer. Patients enrolled in non-curative intent treatment cohorts will have never been treated for their metastatic cancers previously, or have developed advanced/metastatic diseases as relapses of localized cancers previously treated with curative intent therapeutic strategies.
Other: Blood draws
Blood draws are realized at each steps of patient disease management. The volume of each blood drawn is 20 mL for progastrin measurements and additional 5 mL for the dosage of the other tumor markers (PSA, CA19-9, CA125…). The frequency of blood drawn is maximum every 3 weeks (i.e. in case of chemotherapy treatment) and minimum every 6 months (for patients in follow up)




Primary Outcome Measures :
  1. ROC curve AUC regarding diagnostic accuracy of progastrin levels at baseline in cancer patients compared to non-cancer controls [ Time Frame: At baseline ]
    Progastrin concentration in plasma samples will be measured with an ELISA Kit (CancerREAD LAB) provided by ECS Progastrin.


Secondary Outcome Measures :
  1. Longitudinal kinetic of progastrin values during treatments, assessed by modeled kinetic parameters of interest [ Time Frame: 6 years ]

    A nonlinear mixed effect model will be used to model the progastrin measurements done during treatments and follow-up of patients.The effect of each event (chemotherapy, surgery…) on the progastrin value and in the inter-individual variability of production and/or elimination rates of progastrin will be analyzed. Progastrin will be measured by ELISA, and the values will be expressed in pM.

    Measures will be done depending on the treatment received. Chemotherapy, every 3 or 4 weeks. Oral treatments: every 3 to 12 weeks. Surgery or radiotherapy: before and after the treatment. Follow up: concomitantly to the visits scheduled for the regular follow up of the patients.


  2. Nycthemeral and weekly progastrin variations [ Time Frame: every 3 hours within 24 hours for the Nycthemeral cohort, and every week for 2 or 3 weeks for the weekly cohort ]
    24 patients will be selected, upon their agreement and serum high levels, to enter in nychtemer (12 patients) or weekly (12 patients) cohorts. For the Nychtemer cohort, progastrin will be assayed at d1 at 8:00 am; 11:00 am; 2:00 pm; 5:00 pm; 8:00 pm and at d2 at 8:00 For the weekly cohort, progastrin will be assayed Day 1; Day 8; Day 15 and +/- Day 22; ideally on the same hour times. Progastrin will be measured by ELISA, and the values will be expressed in pM.

  3. Determinants of progastrin serum values: hepatic function [ Time Frame: 6 years ]

    A nonlinear mixed effect model will be used to correlate individual values of progastrin (expressed in pM) with individual characteristic on the patient (hepatic function, as measured by the concentration of AST, ALT and bilirubin).

    Measures will be done Chemotherapy, every 3 or 4 weeks. Oral treatments: every 3 to 12 weeks. Surgery or radiotherapy: before and after the treatment. Follow up: concomitantly to the visits scheduled for the regular follow up of the patients


  4. Determinants of progastrin serum values: renal function [ Time Frame: 6 years ]

    A nonlinear mixed effect model will be used to correlate individual values of progastrin (expressed in pM) with individual characteristic on the patient (renal function, as measured by creatinin concentration and creatinin clearance).

    Measures will be done Chemotherapy, every 3 or 4 weeks. Oral treatments: every 3 to 12 weeks. Surgery or radiotherapy: before and after the treatment. Follow up: concomitantly to the visits scheduled for the regular follow up of the patients


  5. Determinants of progastrin serum values: age [ Time Frame: at the inclusion ]
    A nonlinear mixed effect model will be used to correlate the individual characteristics of the patient (age and gender) with progastrin concentration at the inclusion.

  6. Determinants of progastrin serum values: gender [ Time Frame: at the inclusion ]
    A nonlinear mixed effect model will be used to correlate genders with progastrin concentrations at the inclusion.

  7. Overall survival [ Time Frame: 6 years ]

    The relationships between the progastrin kinetics during and after treatment and overall survival will be analyzed. Analyses will be performed separately on patients with curative intent treatment and on patients with palliative intent treatment.

    Measures wil be done At the end of the study (6 years for patients enrolled in curative intent and 5 years for patients enrolled in non-curative intent) or alternatively at the occurrence of progression or relapse.


  8. recurrence free survival [ Time Frame: 6 years ]

    The relationships between the progastrin kinetics during and after treatment and recurrence free survival will be analyzed. Analyses will be performed separately on patients with curative intent treatment and on patients with palliative intent treatment.

    Measures wil be done At the end of the study (6 years for patients enrolled in curative intent and 5 years for patients enrolled in non-curative intent) or alternatively at the occurrence of progression or relapse.


  9. progression free survival [ Time Frame: 6 years ]

    The relationships between the progastrin kinetics during and after treatment and progression free survival will be analyzed. Analyses will be performed separately on patients with curative intent treatment and on patients with palliative intent treatment.

    Measures wil be done At the end of the study (6 years for patients enrolled in curative intent and 5 years for patients enrolled in non-curative intent) or alternatively at the occurrence of progression or relapse.


  10. The tumor size at cancer diagnosis [ Time Frame: At baseline ]
    The size of the tumor will be correlated to progastrin concentration at the time of cancer diagnosis

  11. Complete surgery [ Time Frame: 6 years ]
    The ability of progastrin kinetics during the neoadjuvant period to predict the outcome of the surgery (complete or not) will be analyzed by a ROC curve. If applicable.

  12. time to recurrence (for patients enrolled in curative intent cohorts). [ Time Frame: 6 years ]
    The ability of the progastrin kinetics to predict recurrence free survival (curative cohorts), will be based on parameters estimated with a PK/PD model able to characterize the early kinetics of progastrin during and after the end of treatment and during follow up.

  13. time to progression (for patients enrolled in non-curative intent cohorts) [ Time Frame: 6 years ]
    The ability of the progastrin kinetics to predict progression-free survival (non-curative cohorts) will be based on parameters estimated with a PK/PD model able to characterize the early kinetics of progastrin during and after the end of treatment and during follow up

  14. time to death (whenever it occurred) [ Time Frame: 6 years ]
    The ability of the progastrin kinetics to predict time to death will be based on parameters estimated with a PK/PD model able to characterize the early kinetics of progastrin during and after the end of treatment and during follow up

  15. Comparison of the initial values and of the kinetics of other serum tumor markers (CA15-3, CA 19-9, CA125, CEA, PSA, AFP) with those of progastrin [ Time Frame: at the baseline ]

    The ROC AUC will be compared between classical markers and the prograstrin. Logistic regression will be used to combine the classical marker(s) and the progastrin in order to estimate the diagnostic value of the marker combination.

    progastrin, CA15-3, CA19-9, CA125, CEA, PSA and AFP concentration will be measured on blood sample taken at the inclusion.




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03787056


Contacts
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Contact: Benoit YOU, MD 04 78 86 43 53 ext +33 benoit.you@hu-lyon.fr
Contact: Sara CALATTINI 04 78 86 37 79 ext +33 sara.calattini@chu-lyon.fr

Locations
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France
Service de NEURO-ONCOLOGIE du Groupement Hospitalier EST Recruiting
Bron, France
Contact: Francois DUCRAY, MD       francois.ducray@chu-lyon.fr   
Principal Investigator: Francois DUCRAY, MD         
Service d'ONCOLOGIE DIGESTIVE et HEPATOLOGIE de l'hôpital de la Croix-Rousse Recruiting
Lyon, France
Contact: Marielle GUILLET, MD       marielle.guillet@chu-lyon.fr   
Principal Investigator: Marielle GUILLET, MD         
Sub-Investigator: Philippe MERLE, MD         
Service d'ONCOLOGIE DIGESTIVE et HEPATOLOGIE de l'Hôpital E. Herriot Recruiting
Lyon, France
Contact: Thomas WALTER, MD       thomas.walter@chu-lyon.fr   
Principal Investigator: Thomas WALTER, MD         
Sub-Investigator: Mathieu PIOCHE, MD         
Service d'Oto-Rhino-Laryngologie de l'Hôpital de la Croix-Rousse Recruiting
Lyon, France
Contact: Amandine BRUYAS, MD       amandine.bruyas@chu-lyon.fr   
Principal Investigator: Amandine BRUYAS, MD         
Sub-Investigator: Philippe CERUSE, MD         
Service d'Urologie de l'Hôpital E. Herriot Recruiting
Lyon, France
Contact: Lionel BADET, MD       lionel.badet@chu-lyon.fr   
Principal Investigator: Lionel BADET, MD         
Service de Gynécologie de l'hôpital de la Croix-Rousse Recruiting
Lyon, France
Contact: Marion CORTET, MD       marion.cortet@chu-lyon.fr   
Principal Investigator: Marion CORTET, MD         
Service de Gynécologie du Groupement Hospitalier Est Recruiting
Lyon, France
Contact: Christophe SAJOUS, MD       christophe.sajous@chu-lyon.fr   
Principal Investigator: Christophe SAJOUS, MD         
Service de Pneumologie de l'hôpital de la Croix-Rousse Recruiting
Lyon, France
Contact: Gilles DEVOUASSOUX, MD       gilles.devouassoux@chu-lyon.fr   
Principal Investigator: Gilles DEVOUASSOUX, MD         
Sub-Investigator: Lize KIAKOUAMA, MD         
Service de Pneumologie du Groupement Hospitalier Est Recruiting
Lyon, France
Contact: Michael DURUISSEAUX, MD       michael.duruisseaux@chu-lyon.fr   
Principal Investigator: Michael DURUISSEAUX, MD         
Service d'Hématologie de l'Hôpital Lyon Sud Recruiting
Pierre-Bénite, France
Contact: Lionel KARLIN, MD       lionel.karlin@chu-lyon.fr   
Principal Investigator: Lionel KARLIN, MD         
Service d'ONCOLOGIE DIGESTIVE et HEPATOLOGIE du Centre Hospitalier Lyon Sud Recruiting
Pierre-Bénite, France
Contact: Marion CHAUVENET, MD       marion.chauvenet@chu-lyon.fr   
Principal Investigator: Marion CHAUVENET, MD         
Service d'Oncologie médicale du Centre hospitalier Lyon Sud Recruiting
Pierre-Bénite, France
Contact: Benoit YOU, MD       benoit.you@chu-lyon.fr   
Principal Investigator: Benoit YOU, MD         
Sub-Investigator: Gilles FREYER, MD         
Sub-Investigator: Véronique TRILLET LENOIR, MD         
Sub-Investigator: Denis MAILLET, MD         
Sub-Investigator: Sophie TARTAS, MD         
Sub-Investigator: Nathalie BONNIN, MD         
Sub-Investigator: Julien PERON, MD         
Sub-Investigator: Olivia LE SAUX, MD         
Service d'Urologie de l'hôpital Lyon Sud Recruiting
Pierre-Bénite, France
Contact: Philippe PAPAREL, MD       philippe.paparel@chu-lyon.fr   
Principal Investigator: Philippe PAPAREL, MD         
Service de Chirurgie de l'hôpital Lyon Sud Recruiting
Pierre-Bénite, France
Contact: Olivier GLEHEN, MD       olivier.glehen@chu-lyon.fr   
Principal Investigator: Olivier GLEHEN, MD         
Sub-Investigator: Naoual BAKRIN, MD         
Service de Dermatologie de l'hôpital Lyon Sud Recruiting
Pierre-Bénite, France
Contact: Stephane DALLE, MD       stephane.dalle@chu-lyon.fr   
Principal Investigator: Stephane DALLE, MD         
Sub-Investigator: Mona AMINI, MD         
Service de Gynécologie de l'hôpital Lyon Sud Recruiting
Pierre-Bénite, France
Contact: Pierre Adrien BOLZE, MD       pierre-adrien.bolze@chu-lyon.fr   
Principal Investigator: Pierre Adrien BOLZE, MD         
Service de Pneumologie de l'Hôpital Lyon Sud Recruiting
Pierre-Bénite, France
Contact: Sebastien COURAUD, MD       sebastien.couraud@chu-lyon.fr   
Principal Investigator: Sebastien COURAUD, MD         
Sponsors and Collaborators
Hospices Civils de Lyon
Investigators
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Principal Investigator: Benoit YOU, MD Hospices Civils de Lyon

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Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT03787056     History of Changes
Other Study ID Numbers: 69HCL18_0369
First Posted: December 25, 2018    Key Record Dates
Last Update Posted: December 25, 2018
Last Verified: December 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hospices Civils de Lyon:
dd
TUMOR MARKER
PROGASTRIN

Additional relevant MeSH terms:
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Colorectal Neoplasms
Pancreatic Neoplasms
Glioblastoma
Head and Neck Neoplasms
Lymphoma, B-Cell
Urinary Bladder Neoplasms
Esophageal Neoplasms
Endometrial Neoplasms
Kidney Neoplasms
Carcinoma, Renal Cell
Liver Neoplasms
Carcinoma, Hepatocellular
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Endocrine Gland Neoplasms
Pancreatic Diseases
Endocrine System Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Astrocytoma
Glioma