Avelumab + Paclitaxel/ Ramucirumab als Zweitlinientherapie beim gastro-ösophagealen Adenokarzinom: eine Phase-II-Studie der AIO - RAP-Studie

Phase 1

• Conditions: metastatic gastro-oesophageal cancer; MedDRA version: 21.1Level: LLTClassification code 10066354Term: Adenocarcinoma of the gastroesophageal junctionSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-002938-20-DE
• Lead Sponsor: Charite - Universitätsmedizin Berlin

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-12-03
• Last Update Posted: 9 January 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 59

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.ECOG performance status 0-1
8.Life expectancy > 12 weeks
9.Adequate hematological, hepatic and renal functions:
a)Absolute neutrophil count (ANC) = 1.5 x 109/L
b)Platelet count = 100 x 109/L
c)Hemoglobin = 9 g/dl (may have been transfused)
d)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
e)Estimated creatinine clearance = 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
f)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)
g)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/phenprocomon 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 38
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 21

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 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 or VEGFR inhibitor or any antiangiogenic agent, or prior enrolment in the study
6.Major surgical procedure, open biopsy or significant traumatic injury within 4 weeks prior to start of study treatment;
7.Grade 3-4 GI bleeding within 3 months prior to enrollment
8.History of deep vein thrombosis, pulmonary embolism or any other significant thromboembolism 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.
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
12.Other serious illness or medical conditions prior to study drug administration
a)Clinically significant 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
b)Uncontrolled or poorly controlled hypertension despite optimal medical therapy
c)Current history of chronic diarrhea
d)Active disseminated intravascular coagulation
e)History of gastrointestinal perforation, fistulae or any clinically relevant arterial thromboembolic event within 6 months
f)Active infection
g)Hepatitis B virus or hepatitis C virus infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive)
h)Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent
i)Serious or non-healing wound, ulcer, or bone fracture within 28 days prior to first dose
j)Prior organ transplantation incl. allogenic stem-cell transplantation
k)Other severe acute or chronic medical conditions incl. 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:
a)intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);
b)steroids as premedication for hypersensitivity reactions (e.g., CT scan p

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified