Clinical Trials /

Ramucirumab and Trifluridine/Tipiracil or Paclitaxel for the Treatment of Patients With Previously Treated Advanced Gastric or Gastroesophageal Junction Cancer

NCT04660760

Description:

This phase II trial studies the effect of the combination of ramucirumab and trifluridine/tipiracil or paclitaxel in treating patients with previously treated gastric or gastroesophageal junction cancer that has spread to other places in the body (advanced). Ramucirumab may damage tumor cells by targeting new blood vessel formation. Trifluridine/tipiracil is a chemotherapy pill and that may damage tumor cells by damaging their deoxyribonucleic acid (DNA). Paclitaxel may block cell growth by stopping cell division which may kill tumor cells. Giving ramucirumab and trifluridine/tipiracil will not be worse than ramucirumab and paclitaxel in treating gastric or gastroesophageal junction cancer.

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

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ramucirumab and Trifluridine/Tipiracil or Paclitaxel for the Treatment of Patients With Previously Treated Advanced Gastric or Gastroesophageal Junction Cancer
  • Official Title: Ramucirumab Plus Trifluridine/Tipiracil (TAS-102) for Patients With Previously Treated Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: An Investigator-Initiated, Randomized Non-Inferiority Phase 2 Study

Clinical Trial IDs

  • ORG STUDY ID: ACCRU-GI-1810
  • SECONDARY ID: NCI-2020-11436
  • SECONDARY ID: ACCRU-GI-1810
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT04660760

Conditions

  • Clinical Stage III Gastric Cancer AJCC v8
  • Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Clinical Stage IV Gastric Cancer AJCC v8
  • Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Clinical Stage IVA Gastric Cancer AJCC v8
  • Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Clinical Stage IVB Gastric Cancer AJCC v8
  • Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Locally Advanced Unresectable Gastric Adenocarcinoma
  • Locally Advanced Unresectable Gastroesophageal Junction Adenocarcinoma
  • Metastatic Gastric Adenocarcinoma
  • Metastatic Gastroesophageal Junction Adenocarcinoma
  • Pathologic Stage III Gastric Cancer AJCC v8
  • Pathologic Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Pathologic Stage IIIA Gastric Cancer AJCC v8
  • Pathologic Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Pathologic Stage IIIB Gastric Cancer AJCC v8
  • Pathologic Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Pathologic Stage IIIC Gastric Cancer AJCC v8
  • Pathologic Stage IV Gastric Cancer AJCC v8
  • Pathologic Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Postneoadjuvant Therapy Stage III Gastric Cancer AJCC v8
  • Postneoadjuvant Therapy Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Postneoadjuvant Therapy Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Postneoadjuvant Therapy Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Postneoadjuvant Therapy Stage IV Gastric Cancer AJCC v8
  • Postneoadjuvant Therapy Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Postneoadjuvant Therapy Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Postneoadjuvant Therapy Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8

Interventions

DrugSynonymsArms
PaclitaxelAnzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol KonzentratArm B (paclitaxel, ramucirumab)
RamucirumabAnti-VEGFR-2 Fully Human Monoclonal Antibody IMC-1121B, Cyramza, IMC-1121B, LY3009806, Monoclonal Antibody HGS-ETR2Arm A (TAS-102, ramucirumab)
Trifluridine and Tipiracil HydrochlorideLonsurf, TAS 102, TAS-102, Tipiracil Hydrochloride Mixture with Trifluridine, Trifluridine/Tipiracil, Trifluridine/Tipiracil Hydrochloride Combination Agent TAS-102Arm A (TAS-102, ramucirumab)

Purpose

This phase II trial studies the effect of the combination of ramucirumab and trifluridine/tipiracil or paclitaxel in treating patients with previously treated gastric or gastroesophageal junction cancer that has spread to other places in the body (advanced). Ramucirumab may damage tumor cells by targeting new blood vessel formation. Trifluridine/tipiracil is a chemotherapy pill and that may damage tumor cells by damaging their deoxyribonucleic acid (DNA). Paclitaxel may block cell growth by stopping cell division which may kill tumor cells. Giving ramucirumab and trifluridine/tipiracil will not be worse than ramucirumab and paclitaxel in treating gastric or gastroesophageal junction cancer.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To compare, in a non-inferiority fashion, the progression-free survival (PFS) in patients
      with metastatic refractory gastric/gastroesophageal junction (GEJ) adenocarcinoma receiving
      the combination of ramucirumab with trifluridine and tipiracil hydrochloride (TAS-102) versus
      (vs.) paclitaxel and ramucirumab.

      SECONDARY OBJECTIVES:

      I. To assess overall survival (OS) in this patient population for each regimen. II. Assess
      changes in patient quality of life (QOL) as measured by the linear analogue self-assessment
      (LASA) questionnaire for each regimen.

      III. To determine the safety of the combination of ramucirumab with TAS-102 in this patient
      population.

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM A: Patients receive TAS-102 orally (PO) twice daily (BID) on days 1-5 and 8-12, and
      ramucirumab intravenously (IV) over 30-60 minutes on days 1 and 15. Treatment repeats every
      28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.

      ARM B: Patients receive paclitaxel IV over 1-96 hours on days 1, 8, and 15, and ramucirumab
      IV over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 36 cycles
      in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30-35 days, then every 3
      months for up to 3 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (TAS-102, ramucirumab)ExperimentalPatients receive TAS-102 PO BID on days 1-5 and 8-12, and ramucirumab IV over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.
  • Ramucirumab
  • Trifluridine and Tipiracil Hydrochloride
Arm B (paclitaxel, ramucirumab)Active ComparatorPatients receive paclitaxel IV over 1-96 hours on days 1, 8, and 15, and ramucirumab IV over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.
  • Paclitaxel
  • Ramucirumab

Eligibility Criteria

        Inclusion Criteria:

          -  Age >= 18 years

          -  Histological or cytological confirmation of adenocarcinoma of the stomach or
             gastroesophageal junction

          -  Have locally advanced unresectable or metastatic disease that has progressed =< 180
             days since last treatment

          -  One or more measurable or nonmeasurable evaluable lesions per Response Evaluation
             Criteria in Solid Tumors (RECIST)

          -  Planned for second line treatment defined by failing or were intolerant to previous
             standard chemotherapies containing one or more of the following agents:

               -  Fluoropyrimidine (IV 5-FU or capecitabine) and platinum (cisplatin or
                  oxaliplatin)

               -  Trastuzumab in case of HER2-positive disease

               -  NOTE: For the patients whose disease recurred =< 168 days from the last dose of
                  adjuvant anticancer chemotherapy, that adjuvant anticancer chemotherapy is
                  counted as 1 prior chemotherapy line

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

          -  Ability to swallow oral medications

          -  Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 7 days prior to
             registration)

          -  Platelet count >= 100,000/mm^3 (obtained =< 7 days prior to registration)

          -  Hemoglobin >= 9.0 g/dL (obtained =< 7 days prior to registration)

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 7 days prior to
             registration)

          -  Aspartate transaminase (AST) and alanine transaminase (ALT) =< 3 x ULN ( =< 5.0 x UNL,
             if with liver metastasis) (obtained =< 7 days prior to registration)

          -  International normalized ratio (INR) =< 1.5 x ULN, and a partial thromboplastin time
             (PTT) =< 5 seconds above the ULN (unless receiving anticoagulation therapy) (obtained
             =< 7 days prior to registration)

               -  Note: Patients receiving warfarin must be switched to low molecular weight
                  heparin and have achieved stable coagulation profile prior to first dose of
                  protocol therapy

               -  Note: Patients on full-dose anticoagulation must be on a stable dose (minimum
                  duration 14 days) of oral anticoagulant or low molecular weight heparin (LMWH)

               -  Exception: If receiving warfarin, the patient must have an INR =< 3.0. For
                  heparin and LMWH there should be no active bleeding (that is, no bleeding within
                  14 days prior to first dose of protocol therapy) or pathological condition
                  present that carries a high risk of bleeding (for example, tumor involving major
                  vessels or known varices)

          -  Urinary protein is =< 1+ on dipstick or routine urinalysis (UA; if urine dipstick 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) (obtained =< 7
             days prior to registration)

          -  Creatinine =< 1.5 times the ULN or creatinine clearance (measured via 24-hour urine
             collection) >= 50 mL/minute (that is, if serum creatinine is >= 1.5 times the ULN, a
             24-hour urine collection to calculate creatinine clearance must be performed)
             (obtained =< 7 days prior to registration)

          -  Negative pregnancy test done =< 7 days prior to registration, for women of
             childbearing potential only

          -  Ability to complete questionnaire(s) by themselves or with assistance

          -  Provide informed written consent =< 28 days prior to registration

          -  Willing to return to enrolling institution for follow-up (during the Active Monitoring
             Phase of the study)

          -  Because the teratogenicity of ramucirumab is not known, the patient, if sexually
             active, must be postmenopausal, surgically sterile, or using effective contraception
             (hormonal or barrier methods)

        Exclusion Criteria:

          -  Any of the following because this study involves an investigational agent whose
             genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are
             unknown:

               -  Pregnant women

               -  Nursing women

               -  Women of childbearing potential who are unwilling to employ adequate
                  contraception

          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens

          -  Previous treatment with TAS-102 or ramucirumab

          -  Previous taxane therapy =< 180 days prior to registration

          -  Any grade 3-4 gastrointestinal (GI) bleeding =< 90 days prior to registration

          -  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") =< 90 days prior to registration

          -  Any arterial thromboembolic events, including but not limited to myocardial
             infarction, transient ischemic attack, cerebrovascular accident, or unstable angina,
             =< 180 days prior to registration

          -  Prior history of GI perforation/fistula =< 180 days of registration or risk factors
             for perforation

          -  Serious or nonhealing wound, ulcer, or bone fracture =< 28 days prior to registration

          -  Major surgery =< 28 days prior to first dose of protocol therapy, or minor
             surgery/subcutaneous venous access device placement =< 7 days prior to registration

          -  Elective or planned major surgery to be performed during the course of the clinical
             trial

          -  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. NOTE: Clinically meaningful ascites is defined as ascites from cirrhosis
             requiring diuretics or paracentesis

          -  Uncontrolled or poorly-controlled hypertension (>= 150 mmHg systolic or >= 90 mmHg
             diastolic for >= 4 weeks) despite standard medical management

          -  Immunocompromised and known to be human immunodeficiency virus (HIV) positive and
             currently receiving antiretroviral therapy

               -  NOTE: Patients known to be HIV positive, but without clinical evidence of an
                  immunocompromised state, are eligible for this trial

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Receiving any other investigational agent which would be considered as a treatment for
             the primary neoplasm

          -  Other active malignancy =< 3 years prior to registration. EXCEPTIONS: Non-melanotic
             skin cancer or carcinoma-in-situ of the cervix. NOTE: If there is a history of prior
             malignancy, they must not be receiving other specific treatment for their cancer

          -  Receiving chronic antiplatelet therapy, including dipyridamole or clopidogrel, or
             similar agents. NOTE: Once-daily aspirin use (maximum dose 325 mg/day) is permitted
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival
Time Frame:Up to 1 year
Safety Issue:
Description:Progression free survival is defined as the time interval between randomization date and the date of disease progression or death (referred to as an "event"), whichever occurs first. Disease progression will be determined based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. The median progression free survival will be estimated using the Kaplan-Meier method for each arm, corresponding 95% confidence intervals, and hazard ratio comparing the treatment arm to the control arm will be reported.

Secondary Outcome Measures

Measure:Overall survival (OS)
Time Frame:Up to 3 years
Safety Issue:
Description:Median OS will be estimated using the Kaplan-Meier method. Patients who do not experience death while on study will be censored at the last known date alive. The median OS and corresponding 95% confidence interval will be reported by arm.
Measure:Quality of life (QOL)
Time Frame:Up to 3 years
Safety Issue:
Description:Patient reported QOL outcomes will be collected using the Linear Analog Self-Assessment (LASA) Questionnaire. Data will be collected each cycle. Mean values of the first question (regarding overall QOL) at each cycle will be plotted, and stratified by arm.
Measure:Incidence of adverse events
Time Frame:Up to 3 years
Safety Issue:
Description:Adverse events will be recorded using Common Terminology Criteria for Adverse Events version 5.0. The proportion of patients who experience a grade 3+ adverse event at least possibly related to treatment will be reported by arm.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Academic and Community Cancer Research United

Last Updated

January 22, 2021