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

NCT03966118 | Unknown Phase 2 DMC

• 1 other identifier: RAP-Trial
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

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

Conditions

Gastroesophageal Junction Adenocarcinoma; Adenocarcinoma of the Stomach

Keywords

2nd line; Ramucirumab; Avelumab; Paclitaxel; gastric cancer

Outcome Measures

Primary Outcomes (1)

• Overall Survival Rate at 6 months

  patients alive at 6 months

  6 months

Secondary Outcomes (14)

• Overall Survival

  40 months

• Overall Survival Rate at 12 months

  12 months

• Progression Free Survival

  40 months

• Progression Free Survival Rate at 6 months according to RECIST v1.1

  6 months

• Progression Free Survival Rate at 12 months according to RECIST v1.1

  12 months

Study Arms (1)

Ramucirumab + Avelumab + Paclitaxel

EXPERIMENTAL

Single-Arm

Drug: Avelumab; Drug: Ramucirumab; Drug: Paclitaxel

Interventions

Avelumab DRUG

Avelumab 1mg/kg Day 1 and Day 15 of a 28-day cycle

Ramucirumab + Avelumab + Paclitaxel

Ramucirumab DRUG

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

Ramucirumab + Avelumab + Paclitaxel

Paclitaxel DRUG

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

Ramucirumab + Avelumab + Paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent
• Male or female ≥ 18 years of Age
• Histologically proven gastric adenocarcinoma including adenocarcinoma of the esophagogastric junction
• Metastatic or locally advanced disease, not amenable to potentially curative resection
• 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.
• Measurable or non-measurable but evaluable disease determined using guidelines RECIST 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Life expectancy \> 12 weeks
• Adequate hematological, hepatic and renal functions:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• Hemoglobin ≥ 9 g/dl (may have been transfused)
• 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
• Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
• 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)

You may not qualify if:

• Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy not indicated in the study protocol
• Previous therapy with, paclitaxel or ramucirumab or pretreatment with a PD-1, PD-L1 Inhibitor
• Current treatment with any anti-cancer therapy ≤ 2 weeks prior to study treatment start unless rapidly progressing disease is measured
• Previous exposure to a VEGF (vascular endothelial growth factor) or VEGFR inhibitor or any antiangiogenic agent, or prior enrolment in this study
• 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
• Grade 3-4 GI bleeding within 3 months prior to enrollment
• 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
• 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
• Known brain or leptomeningeal metastases
• 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)
• Other serious illness or medical conditions prior to study drug administration
• 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
• Uncontrolled or poorly controlled hypertension despite optimal medical therapy
• Current history of chronic diarrhea

Sponsors & Collaborators

• P. C. Thuss-Patience: lead

Study Sites (1)

Charité Universitätsmedizin Berlin

Berlin, 13353, Germany

RECRUITING

Related Publications (2)

• 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.

  PMID: 30515672 BACKGROUND

• Thuss-Patience P, Hogner A, Goekkurt E, Stahl M, Kretzschmar A, Gotze T, Stocker G, Reichardt P, Kullmann F, Pink D, Bartels P, Jarosch A, Hinke A, Schultheiss C, Paschold L, Stein A, Binder M. Ramucirumab, Avelumab, and Paclitaxel as Second-Line Treatment in Esophagogastric Adenocarcinoma: The Phase 2 RAP (AIO-STO-0218) Nonrandomized Controlled Trial. JAMA Netw Open. 2024 Jan 2;7(1):e2352830. doi: 10.1001/jamanetworkopen.2023.52830.

  PMID: 38261316 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

avelumab; Ramucirumab; Paclitaxel

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Peter Thuss-Patience, MD

  Charité-University Medicine (Berlin, Germany)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peter Thuss-Patience, MD

CONTACT

+4930450553111; peter.thuss@charite.de

Lorenz Mario

CONTACT

+4930450653868; ma.lorenz@charite.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD (Principal Investigator)

Model Details: Avelumab + Paclitaxel / Ramucirumab

Study Record Dates

• First Submitted: February 12, 2019
• First Posted: May 29, 2019
• Study Start: April 1, 2019
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2023
• Last Updated: June 3, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)