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出境医 / 临床实验 / Avelumab + Paclitaxel/ Ramucirumab (RAP) as Second Line Treatment in Gastro-esophageal Adenocarcinoma (AIO-STO-0218)

Avelumab + Paclitaxel/ Ramucirumab (RAP) as Second Line Treatment in Gastro-esophageal Adenocarcinoma (AIO-STO-0218)

Study Description
Brief Summary:
Avelumab + Paclitaxel/ Ramucirumab as second line treatment in gastro-esophageal adenocarcinoma following first-line therapy with platinum and fluoropyrimidine doublet with or without anthracycline, docetaxel or trastuzumab

Condition or disease Intervention/treatment Phase
Gastroesophageal Junction Adenocarcinoma Adenocarcinoma of the Stomach Drug: Avelumab Drug: Ramucirumab Drug: Paclitaxel Phase 2

Detailed Description:
Patients with adenocarcinoma of the gastro-esophageal junction or the stomach who have documented progression after being treated with a 1st line chemotherapy which contained at least a platinum and 5-FU (5-Flourouracil)can be included. All patients will receive a standard second line therapy with paclitaxel and ramucirumab plus the investigational drug avelumab, a checkpoint inhibitor. Clinical and radiographic assessment will be performed regularly. Patients will be treated until disease progression, untolerable toxicity or withdrawal of consent.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 59 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Avelumab + Paclitaxel / Ramucirumab
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Avelumab + Paclitaxel/ Ramucirumab as Second Line Treatment in Gastro-esophageal Adenocarcinoma: a Phase II Trial of the AIO (The RAP-Trial)
Actual Study Start Date : April 1, 2019
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2023
Arms and Interventions
Arm Intervention/treatment
Experimental: Ramucirumab + Avelumab + Paclitaxel
Single-Arm
Drug: Avelumab
Avelumab 1mg/kg Day 1 and Day 15 of a 28-day cycle

Drug: Ramucirumab
Ramucirumab 8mg/kg on Day 1 and Day 15 of a 28-day cycle

Drug: Paclitaxel
Paclitaxel 80mg/m2 on Day 1, Day 8 and Day 15 of a 28-day cycle

Outcome Measures
Primary Outcome Measures :
  1. Overall Survival Rate at 6 months [ Time Frame: 6 months ]
    patients alive at 6 months


Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: 40 months ]
    patients alive using Kaplan Meyer

  2. Overall Survival Rate at 12 months [ Time Frame: 12 months ]
    patients alive at 12 months

  3. Progression Free Survival [ Time Frame: 40 months ]
    Patients showing progressive disease

  4. Progression Free Survival Rate at 6 months according to RECIST v1.1 [ Time Frame: 6 months ]
    Patients showing progressive disease at 6 months

  5. Progression Free Survival Rate at 12 months according to RECIST v1.1 [ Time Frame: 12 months ]
    Patients showing progressive disease at 12 months

  6. Number of participants with treatment related adverse events (AE) as assessed by common toxicity criteria CTC AE v5.0 [ Time Frame: 40 months ]
    Patients reported with adverse events

  7. Number of participants to whom the treatment could me administered as planned (feasibility). [ Time Frame: 40 months ]
    number of patients who received treatment

  8. Best response according to RECIST v1.1 [ Time Frame: 40 months ]
    Proportion of patients who show response

  9. Confirmed response rate according to RECIST v1.1 [ Time Frame: 40 months ]
    Proportion of patients who show confirmed response

  10. Duration of response [ Time Frame: 40 months ]
    time how long response lasts

  11. Amount of Tumor infiltrating lymphocytes and TCRβ & IgH; clonal evolution [ Time Frame: 40 months ]
    liquid biopsy and next generation sequencing

  12. Subgroup analyses: number of participants with Programmed Death receptor Ligand 1 (PD-L1) positive tumors. [ Time Frame: 40 months ]
    number of patients with PD-L1 positive tumors in pathology assessment

  13. Progression Free Survival (PFS) according to modified RECIST [ Time Frame: 40 months ]
    Proportion of patients who show progressive disease

  14. Overall Response Rate (ORR) according to modified RECIST [ Time Frame: 40 months ]
    Proportion of patients responding


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

Inclusion Criteria:

  1. Signed written informed consent
  2. Male or female ≥ 18 years of Age
  3. Histologically proven gastric adenocarcinoma including adenocarcinoma of the esophagogastric junction
  4. Metastatic or locally advanced disease, not amenable to potentially curative resection
  5. Documented objective radiological or clinical disease progression during or within 6 months of the last dose of first-line platinum and fluoropyrimidine doublet with or without anthracycline, docetaxel or trastuzumab. Neoadjuvant/adjuvant treatment is not counted unless progression occurs <6 months after completion of the treatment. In these cases neoadjuvant/adjuvant treatment is counted as first line.
  6. Measurable or non-measurable but evaluable disease determined using guidelines RECIST 1.1
  7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  8. Life expectancy > 12 weeks
  9. Adequate hematological, hepatic and renal functions:

    1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
    2. Platelet count ≥ 100 x 109/L
    3. Hemoglobin ≥ 9 g/dl (may have been transfused)
    4. Total bilirubin ≤ 1.5 times the upper limit of normal (ULN) and AST and ALT ≤ 2.5 x ULN in absence of liver metastases, or ≤ 5 x ULN in presence of liver metastases; AP ≤ 5 x ULN
    5. Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
    6. Urinary protein ≤ 1+ on dipstick or routine urinalysis (UA; if urinedipstick or routine analysis is ≥ 2+, a 24-hour urine collection for protein must demonstrate < 1000 mg of protein in 24 hours to allow participation in this protocol)
    7. Adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1,5 ULN, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy). Patients receiving warfarin/phenprocoumon must be switched to low molecular weight heparin and have achieved stable coagulation profile prior to first dose of protocol therapy.
  10. Women of child-bearing potential must have a negative urine or serum pregnancy test
  11. Highly effective contraception for both male and female subjects throughout the study and for at least 30 days after last avelumab and at least 3 months after last ramucirumab treatment administration if the risk of conception exists
  12. Ability to comply with scheduled assessments and with management of toxicities.

Exclusion Criteria:

  1. Other tumor type than adenocarcinoma (e.g. leiomyosarcoma, lymphoma) or a second cancer except in patients with squamous or basal cell carcinoma of the skin or carcinoma in situ of the cervix that has been effectively treated. Patients curatively treated for any other malignancy and disease-free for at least 5 years will be discussed with the sponsor before inclusion
  2. Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy not indicated in the study protocol
  3. Previous therapy with, paclitaxel or ramucirumab or pretreatment with a PD-1, PD-L1 Inhibitor
  4. Current treatment with any anti-cancer therapy ≤ 2 weeks prior to study treatment start unless rapidly progressing disease is measured
  5. Previous exposure to a VEGF (vascular endothelial growth factor) or VEGFR inhibitor or any antiangiogenic agent, or prior enrolment in this study
  6. Major surgical procedure, open biopsy or significant traumatic injury within 4 weeks prior to start of study treatment; anticipation of need for major surgical procedure (e.g. impending bowel obstruction) during the course of the study
  7. Grade 3-4 GI bleeding within 3 months prior to enrollment
  8. History of deep vein thrombosis (DVT), pulmonary embolism (PE), or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to first dose of protocol therapy
  9. Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis
  10. Known brain or leptomeningeal metastases
  11. Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v5.0 Grade ≥ 3)
  12. Other serious illness or medical conditions prior to study drug administration

    1. Clinically significant (i.e., active) cardiovascular disease:

      cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication

    2. Uncontrolled or poorly controlled hypertension despite optimal medical therapy
    3. Current history of chronic diarrhea
    4. Active disseminated intravascular coagulation
    5. History of gastrointestinal perforation, fistulae or any clinically relevant arterial thromboembolic event within 6 months
    6. Active infection that, in the opinion of the investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the subject to receive study drug
    7. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive)
    8. Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
    9. Serious or non-healing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy
    10. Prior organ transplantation including allogenic stem-cell transplantation
    11. Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
  13. Current use of immunosuppressive medication,

    EXCEPT for the following:

    1. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);
    2. steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication
    3. short term steroids to prevent chemotherapy induced Nausea
  14. The patient is receiving chronic antiplatelet therapy, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325 mg/day) is permitted
  15. Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
  16. Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
  17. Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days but at least 5 half-lives of the IMP prior to treatment start
  18. Known drug abuse/ alcohol abuse
  19. Persisting toxicity related to prior therapy (NCI CTCAE v. 5.0 Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable
  20. Subject pregnant or breast feeding, or planning to become pregnant within 3 months after the end of Treatment
  21. Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 30 days (male or female) with avelumab and 3 months with ramucirumab after the end of Treatment
  22. Patients known to have a HER2 positive cancer who have not been treated already with a HER2 targeting Agent
  23. Patients with a psychiatric illness or patients imprisoned or working in the Institution of the treating physician.
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Peter Thuss-Patience, MD +4930450553111 peter.thuss@charite.de
Contact: Lorenz Mario +4930450653868 ma.lorenz@charite.de

Locations
Layout table for location information
Germany
Charité Universitätsmedizin Berlin Recruiting
Berlin, Germany, 13353
Contact: Peter Thuss-Patience, MD    +49 30 450 553193    peter.thuss@charite.de   
Contact: Mario Lorenz    +49 30 450 653868    anica.hoegner@charite.de   
Sponsors and Collaborators
P. C. Thuss-Patience
Investigators
Layout table for investigator information
Principal Investigator: Peter Thuss-Patience, MD Charité - University Medicine Berlin, Germany
Tracking Information
First Submitted Date  ICMJE February 12, 2019
First Posted Date  ICMJE May 29, 2019
Last Update Posted Date June 3, 2019
Actual Study Start Date  ICMJE April 1, 2019
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 27, 2019)
Overall Survival Rate at 6 months [ Time Frame: 6 months ]
patients alive at 6 months
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 30, 2019)
  • Overall Survival [ Time Frame: 40 months ]
    patients alive using Kaplan Meyer
  • Overall Survival Rate at 12 months [ Time Frame: 12 months ]
    patients alive at 12 months
  • Progression Free Survival [ Time Frame: 40 months ]
    Patients showing progressive disease
  • Progression Free Survival Rate at 6 months according to RECIST v1.1 [ Time Frame: 6 months ]
    Patients showing progressive disease at 6 months
  • Progression Free Survival Rate at 12 months according to RECIST v1.1 [ Time Frame: 12 months ]
    Patients showing progressive disease at 12 months
  • Number of participants with treatment related adverse events (AE) as assessed by common toxicity criteria CTC AE v5.0 [ Time Frame: 40 months ]
    Patients reported with adverse events
  • Number of participants to whom the treatment could me administered as planned (feasibility). [ Time Frame: 40 months ]
    number of patients who received treatment
  • Best response according to RECIST v1.1 [ Time Frame: 40 months ]
    Proportion of patients who show response
  • Confirmed response rate according to RECIST v1.1 [ Time Frame: 40 months ]
    Proportion of patients who show confirmed response
  • Duration of response [ Time Frame: 40 months ]
    time how long response lasts
  • Amount of Tumor infiltrating lymphocytes and TCRβ & IgH; clonal evolution [ Time Frame: 40 months ]
    liquid biopsy and next generation sequencing
  • Subgroup analyses: number of participants with Programmed Death receptor Ligand 1 (PD-L1) positive tumors. [ Time Frame: 40 months ]
    number of patients with PD-L1 positive tumors in pathology assessment
  • Progression Free Survival (PFS) according to modified RECIST [ Time Frame: 40 months ]
    Proportion of patients who show progressive disease
  • Overall Response Rate (ORR) according to modified RECIST [ Time Frame: 40 months ]
    Proportion of patients responding
Original Secondary Outcome Measures  ICMJE
 (submitted: May 27, 2019)
  • Overall Survival [ Time Frame: 40 months ]
    patients alive using Kaplan Meyer
  • Overall Survival Rate at 12 months [ Time Frame: 12 months ]
    patients alive at 12 months
  • Progression Free Survival [ Time Frame: 40 months ]
    Patients showing progressive disease
  • Progression Free Survival Rate at 6 months according to RECIST v1.1 [ Time Frame: 6 months ]
    Patients showing progressive disease at 6 months
  • Progression Free Survival Rate at 12 months according to RECIST v1.1 [ Time Frame: 12 months ]
    Patients showing progressive disease at 12 months
  • Number of participants with treatment related adverse events as assessed by CTC AE v5.0 [ Time Frame: 40 months ]
    Patients reported with adverse events
  • Number of participants to whom the treatment could me administered as planned (feasibility). [ Time Frame: 40 months ]
    number of patients who received treatment
  • Best response according to RECIST v1.1 [ Time Frame: 40 months ]
    Proportion of patinets who show response
  • Confirmed response rate according to RECIST v1.1 [ Time Frame: 40 months ]
    Proportion of patinets who show confirmed response
  • Duration of response [ Time Frame: 40 months ]
    time how ling Response lasts
  • Amount of Tumor infiltrating lymphocytes and TCRβ & IgH; clonal evolution [ Time Frame: 40 months ]
    liqid biopsy and next gerenration sequencing
  • Subgroup analyses: number of participants with PD-L1 positive tumors. [ Time Frame: 40 months ]
    numebr of patients with PF-L1 positive Tumors in pathology assessment
  • Progression Free Survival (PFS) according to modified RECIST [ Time Frame: 40 months ]
    Proportion of patients who Show porgressive disease
  • Overall Response Rate (ORR) according to modified RECIST [ Time Frame: 40 months ]
    Proportion of patients responding
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Avelumab + Paclitaxel/ Ramucirumab (RAP) as Second Line Treatment in Gastro-esophageal Adenocarcinoma
Official Title  ICMJE Avelumab + Paclitaxel/ Ramucirumab as Second Line Treatment in Gastro-esophageal Adenocarcinoma: a Phase II Trial of the AIO (The RAP-Trial)
Brief Summary Avelumab + Paclitaxel/ Ramucirumab as second line treatment in gastro-esophageal adenocarcinoma following first-line therapy with platinum and fluoropyrimidine doublet with or without anthracycline, docetaxel or trastuzumab
Detailed Description Patients with adenocarcinoma of the gastro-esophageal junction or the stomach who have documented progression after being treated with a 1st line chemotherapy which contained at least a platinum and 5-FU (5-Flourouracil)can be included. All patients will receive a standard second line therapy with paclitaxel and ramucirumab plus the investigational drug avelumab, a checkpoint inhibitor. Clinical and radiographic assessment will be performed regularly. Patients will be treated until disease progression, untolerable toxicity or withdrawal of consent.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Avelumab + Paclitaxel / Ramucirumab
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Gastroesophageal Junction Adenocarcinoma
  • Adenocarcinoma of the Stomach
Intervention  ICMJE
  • Drug: Avelumab
    Avelumab 1mg/kg Day 1 and Day 15 of a 28-day cycle
  • Drug: Ramucirumab
    Ramucirumab 8mg/kg on Day 1 and Day 15 of a 28-day cycle
  • Drug: Paclitaxel
    Paclitaxel 80mg/m2 on Day 1, Day 8 and Day 15 of a 28-day cycle
Study Arms  ICMJE Experimental: Ramucirumab + Avelumab + Paclitaxel
Single-Arm
Interventions:
  • Drug: Avelumab
  • Drug: Ramucirumab
  • Drug: Paclitaxel
Publications * Doi T, Iwasa S, Muro K, Satoh T, Hironaka S, Esaki T, Nishina T, Hara H, Machida N, Komatsu Y, Shimada Y, Otsu S, Shimizu S, Watanabe M. Phase 1 trial of avelumab (anti-PD-L1) in Japanese patients with advanced solid tumors, including dose expansion in patients with gastric or gastroesophageal junction cancer: the JAVELIN Solid Tumor JPN trial. Gastric Cancer. 2019 Jul;22(4):817-827. doi: 10.1007/s10120-018-0903-1. Epub 2018 Dec 4.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 27, 2019)
59
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2023
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Signed written informed consent
  2. Male or female ≥ 18 years of Age
  3. Histologically proven gastric adenocarcinoma including adenocarcinoma of the esophagogastric junction
  4. Metastatic or locally advanced disease, not amenable to potentially curative resection
  5. Documented objective radiological or clinical disease progression during or within 6 months of the last dose of first-line platinum and fluoropyrimidine doublet with or without anthracycline, docetaxel or trastuzumab. Neoadjuvant/adjuvant treatment is not counted unless progression occurs <6 months after completion of the treatment. In these cases neoadjuvant/adjuvant treatment is counted as first line.
  6. Measurable or non-measurable but evaluable disease determined using guidelines RECIST 1.1
  7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  8. Life expectancy > 12 weeks
  9. Adequate hematological, hepatic and renal functions:

    1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
    2. Platelet count ≥ 100 x 109/L
    3. Hemoglobin ≥ 9 g/dl (may have been transfused)
    4. Total bilirubin ≤ 1.5 times the upper limit of normal (ULN) and AST and ALT ≤ 2.5 x ULN in absence of liver metastases, or ≤ 5 x ULN in presence of liver metastases; AP ≤ 5 x ULN
    5. Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
    6. Urinary protein ≤ 1+ on dipstick or routine urinalysis (UA; if urinedipstick or routine analysis is ≥ 2+, a 24-hour urine collection for protein must demonstrate < 1000 mg of protein in 24 hours to allow participation in this protocol)
    7. Adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1,5 ULN, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy). Patients receiving warfarin/phenprocoumon must be switched to low molecular weight heparin and have achieved stable coagulation profile prior to first dose of protocol therapy.
  10. Women of child-bearing potential must have a negative urine or serum pregnancy test
  11. Highly effective contraception for both male and female subjects throughout the study and for at least 30 days after last avelumab and at least 3 months after last ramucirumab treatment administration if the risk of conception exists
  12. Ability to comply with scheduled assessments and with management of toxicities.

Exclusion Criteria:

  1. Other tumor type than adenocarcinoma (e.g. leiomyosarcoma, lymphoma) or a second cancer except in patients with squamous or basal cell carcinoma of the skin or carcinoma in situ of the cervix that has been effectively treated. Patients curatively treated for any other malignancy and disease-free for at least 5 years will be discussed with the sponsor before inclusion
  2. Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy not indicated in the study protocol
  3. Previous therapy with, paclitaxel or ramucirumab or pretreatment with a PD-1, PD-L1 Inhibitor
  4. Current treatment with any anti-cancer therapy ≤ 2 weeks prior to study treatment start unless rapidly progressing disease is measured
  5. Previous exposure to a VEGF (vascular endothelial growth factor) or VEGFR inhibitor or any antiangiogenic agent, or prior enrolment in this study
  6. Major surgical procedure, open biopsy or significant traumatic injury within 4 weeks prior to start of study treatment; anticipation of need for major surgical procedure (e.g. impending bowel obstruction) during the course of the study
  7. Grade 3-4 GI bleeding within 3 months prior to enrollment
  8. History of deep vein thrombosis (DVT), pulmonary embolism (PE), or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to first dose of protocol therapy
  9. Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis
  10. Known brain or leptomeningeal metastases
  11. Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v5.0 Grade ≥ 3)
  12. Other serious illness or medical conditions prior to study drug administration

    1. Clinically significant (i.e., active) cardiovascular disease:

      cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication

    2. Uncontrolled or poorly controlled hypertension despite optimal medical therapy
    3. Current history of chronic diarrhea
    4. Active disseminated intravascular coagulation
    5. History of gastrointestinal perforation, fistulae or any clinically relevant arterial thromboembolic event within 6 months
    6. Active infection that, in the opinion of the investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the subject to receive study drug
    7. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive)
    8. Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
    9. Serious or non-healing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy
    10. Prior organ transplantation including allogenic stem-cell transplantation
    11. Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
  13. Current use of immunosuppressive medication,

    EXCEPT for the following:

    1. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);
    2. steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication
    3. short term steroids to prevent chemotherapy induced Nausea
  14. The patient is receiving chronic antiplatelet therapy, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325 mg/day) is permitted
  15. Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
  16. Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
  17. Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days but at least 5 half-lives of the IMP prior to treatment start
  18. Known drug abuse/ alcohol abuse
  19. Persisting toxicity related to prior therapy (NCI CTCAE v. 5.0 Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable
  20. Subject pregnant or breast feeding, or planning to become pregnant within 3 months after the end of Treatment
  21. Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 30 days (male or female) with avelumab and 3 months with ramucirumab after the end of Treatment
  22. Patients known to have a HER2 positive cancer who have not been treated already with a HER2 targeting Agent
  23. Patients with a psychiatric illness or patients imprisoned or working in the Institution of the treating physician.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Peter Thuss-Patience, MD +4930450553111 peter.thuss@charite.de
Contact: Lorenz Mario +4930450653868 ma.lorenz@charite.de
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03966118
Other Study ID Numbers  ICMJE RAP-Trial
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party P. C. Thuss-Patience, Charite University, Berlin, Germany
Study Sponsor  ICMJE P. C. Thuss-Patience
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Peter Thuss-Patience, MD Charité - University Medicine Berlin, Germany
PRS Account Charite University, Berlin, Germany
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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