Clinical Trials /

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

NCT03966118

Description:

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

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: RAP-Trial
  • NCT ID: NCT03966118

Conditions

  • Gastroesophageal Junction Adenocarcinoma
  • Adenocarcinoma of the Stomach

Interventions

DrugSynonymsArms
AvelumabRamucirumab + Avelumab + Paclitaxel
RamucirumabRamucirumab + Avelumab + Paclitaxel
PaclitaxelRamucirumab + Avelumab + Paclitaxel

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Ramucirumab + Avelumab + PaclitaxelExperimentalSingle-Arm
  • Avelumab
  • Ramucirumab
  • Paclitaxel

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival Rate at 6 months
Time Frame:6 months
Safety Issue:
Description:patients alive at 6 months

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:40 months
Safety Issue:
Description:patients alive using Kaplan Meyer
Measure:Overall Survival Rate at 12 months
Time Frame:12 months
Safety Issue:
Description:patients alive at 12 months
Measure:Progression Free Survival
Time Frame:40 months
Safety Issue:
Description:Patients showing progressive disease
Measure:Progression Free Survival Rate at 6 months according to RECIST v1.1
Time Frame:6 months
Safety Issue:
Description:Patients showing progressive disease at 6 months
Measure:Progression Free Survival Rate at 12 months according to RECIST v1.1
Time Frame:12 months
Safety Issue:
Description:Patients showing progressive disease at 12 months
Measure:Number of participants with treatment related adverse events (AE) as assessed by common toxicity criteria CTC AE v5.0
Time Frame:40 months
Safety Issue:
Description:Patients reported with adverse events
Measure:Number of participants to whom the treatment could me administered as planned (feasibility).
Time Frame:40 months
Safety Issue:
Description:number of patients who received treatment
Measure:Best response according to RECIST v1.1
Time Frame:40 months
Safety Issue:
Description:Proportion of patients who show response
Measure:Confirmed response rate according to RECIST v1.1
Time Frame:40 months
Safety Issue:
Description:Proportion of patients who show confirmed response
Measure:Duration of response
Time Frame:40 months
Safety Issue:
Description:time how long response lasts
Measure:Amount of Tumor infiltrating lymphocytes and TCRβ & IgH; clonal evolution
Time Frame:40 months
Safety Issue:
Description:liquid biopsy and next generation sequencing
Measure:Subgroup analyses: number of participants with Programmed Death receptor Ligand 1 (PD-L1) positive tumors.
Time Frame:40 months
Safety Issue:
Description:number of patients with PD-L1 positive tumors in pathology assessment
Measure:Progression Free Survival (PFS) according to modified RECIST
Time Frame:40 months
Safety Issue:
Description:Proportion of patients who show progressive disease
Measure:Overall Response Rate (ORR) according to modified RECIST
Time Frame:40 months
Safety Issue:
Description:Proportion of patients responding

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:P. C. Thuss-Patience

Trial Keywords

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

Last Updated

June 3, 2019