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Gastroesophageal Junction AdenocarcinomaPhase 2AIO-STO-0218NCT03966118

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

A Phase 2 study testing Avelumab, Ramucirumab and Paclitaxel in people with Gastroesophageal Junction Adenocarcinoma and Adenocarcinoma of the Stomach, run by P. C. Thuss-Patience at 1 site in Germany.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Avelumab, Ramucirumab and Paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
59 participants
Where
1 siteGermany
Study dates
1 Apr 2019to Sep 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)
  • 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.
  • Women of child-bearing potential must have a negative urine or serum pregnancy test
  • 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
  • Ability to comply with scheduled assessments and with management of toxicities.

Who cannot join

  • 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
  • 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
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  • 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
  • Active disseminated intravascular coagulation
  • History of gastrointestinal perforation, fistulae or any clinically relevant arterial thromboembolic event within 6 months
  • 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
  • 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)
  • 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.
  • Serious or non-healing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy
  • Prior organ transplantation including allogenic stem-cell transplantation
  • 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
  • Current use of immunosuppressive medication,
  • EXCEPT for the following:
  • intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);
  • steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication
  • short term steroids to prevent chemotherapy induced Nausea
  • 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
  • Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
  • Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
  • 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
  • Known drug abuse/ alcohol abuse
  • 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
  • Subject pregnant or breast feeding, or planning to become pregnant within 3 months after the end of Treatment
  • 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
  • Patients known to have a HER2 positive cancer who have not been treated already with a HER2 targeting Agent
  • Patients with a psychiatric illness or patients imprisoned or working in the Institution of the treating physician.

Trial locations and contacts

1 site in 1 country.

Peter Thuss-Patience, MD contact

+4930450553111

peter.thuss@charite.de

Lorenz Mario contact

+4930450653868

ma.lorenz@charite.de

Germany1 site, 1 recruiting

  • Charité Universitätsmedizin Berlin

    Berlin, 13353

    Peter Thuss-Patience, MD, +49 30 450 553193, peter.thuss@charite.de

    Mario Lorenz, +49 30 450 653868, anica.hoegner@charite.de

    Recruiting

Other trials in Germany

About this study

Official title: Avelumab + Paclitaxel/ Ramucirumab as Second Line Treatment in Gastro-esophageal Adenocarcinoma: a Phase II Trial of the AIO (The RAP-Trial)

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

Read the 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.

Being tested
Avelumab, Ramucirumab, Paclitaxel
Keywords
2nd line, Ramucirumab, Avelumab, Paclitaxel, gastric cancer
Medical subject headings
Stomach Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AvelumabDrug

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

  • RamucirumabDrug

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

  • PaclitaxelDrug

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

Study groups in NCT03966118
Study groupRoleWhat they receive
Ramucirumab + Avelumab + PaclitaxelExperimentalSingle-Arm
Receives: Drug: Avelumab; Drug: Ramucirumab; Drug: Paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival Rate at 6 months

    patients alive at 6 months

    Measured: 6 months

Secondary outcomes (14)

  1. Overall Survival

    patients alive using Kaplan Meyer

    Measured: 40 months

  2. Overall Survival Rate at 12 months

    patients alive at 12 months

    Measured: 12 months

  3. Progression Free Survival

    Patients showing progressive disease

    Measured: 40 months

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

    Patients showing progressive disease at 6 months

    Measured: 6 months

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

    Patients showing progressive disease at 12 months

    Measured: 12 months

  6. Number of participants with treatment related adverse events (AE) as assessed by common toxicity criteria CTC AE v5.0

    Patients reported with adverse events

    Measured: 40 months

  7. Number of participants to whom the treatment could me administered as planned (feasibility).

    number of patients who received treatment

    Measured: 40 months

  8. Best response according to RECIST v1.1

    Proportion of patients who show response

    Measured: 40 months

  9. Confirmed response rate according to RECIST v1.1

    Proportion of patients who show confirmed response

    Measured: 40 months

  10. Duration of response

    time how long response lasts

    Measured: 40 months

  11. Amount of Tumor infiltrating lymphocytes and TCRβ & IgH; clonal evolution

    liquid biopsy and next generation sequencing

    Measured: 40 months

  12. Subgroup analyses: number of participants with Programmed Death receptor Ligand 1 (PD-L1) positive tumors.

    number of patients with PD-L1 positive tumors in pathology assessment

    Measured: 40 months

  13. Progression Free Survival (PFS) according to modified RECIST

    Proportion of patients who show progressive disease

    Measured: 40 months

  14. Overall Response Rate (ORR) according to modified RECIST

    Proportion of patients responding

    Measured: 40 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 May 2019
  2. Study start1 Apr 2019
  3. Primary completionSep 2022 (estimated)
  4. Study completionSep 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Avelumab + Paclitaxel / Ramucirumab
Masking
None (open label)
Enrolment
59 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03966118
Sponsor's protocol ID
RAP-Trial
Acronym
AIO-STO-0218
Status last verified
May 2019
First submitted
12 Feb 2019
Last updated
3 Jun 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

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.

    PubMed 30515672

  • 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.

    PubMed 38261316

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Avelumab, Ramucirumab and Paclitaxel in people with Gastroesophageal Junction Adenocarcinoma and Adenocarcinoma of the Stomach, run by P. C. Thuss-Patience at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 3 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Peter Thuss-Patience, MD (+4930450553111, peter.thuss@charite.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival Rate at 6 months (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03966118, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2019.

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