Ramucirumab Plus TAS-102 in Patients With Advanced or Metastatic Gastric Adenocarcinoma or the Gastroesophageal Junction

NCT04517747 | Completed DMC

• 1 other identifier: RE-ExPEL
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 5

Brief Summary

The objective of this study is to determine whether a combination of ramucirumab, beyond progression after a SOC 2nd line ramucirumab based pre-treatment (Ram beyond progression) in patients with locally advanced or metastatic adenocarcinoma, plus TAS-102 shows good tolerability without safety issues regarding the serious adverse event rate of any cause, and whether the combination shows positive signals regarding efficacy in the secondary endpoints (e.g. prolongation of progression-free survival of TAS-102 plus ramucirumab compared with TAS-102 monotherapy - historical data according to TAGS trial).

Conditions

Gastric Adenocarcinoma; Metastatic Adenocarcinoma of the Gastroesophageal Junction

Outcome Measures

Primary Outcomes (1)

• Tolerability and toxicity: rate of serious adverse events (SAEs) of any cause

  The primary endpoint of the study is tolerability and toxicity, defined by the rate of serious adverse events (SAEs) of any cause according to CTCAE v5.0

  Frist Treatment until 30 days after end of treatment, up to 5 months

Secondary Outcomes (9)

• Rate of treatment-related AEs and SAE

  Frist Treatment until 30 days after end of treatment, up to 5 months

• Adverse events for neutropenia

  Frist Treatment until 30 days after end of treatment, up to 5 months

• Adverse events for anemia

  Frist Treatment until 30 days after end of treatment, up to 5 months

• Adverse events for leucopenia

  Frist Treatment until 30 days after end of treatment, up to 5 months

• Adverse events for thrombocytopenia

  Frist Treatment until 30 days after end of treatment, up to 5 months

Study Arms (1)

Ramucirumab plus TAS-102

EXPERIMENTAL

Ramucirumab 8 mg/kg i.v. on day 1 and day 15 of a 28-day cycle and TAS-102 35 mg/m2/dose p.o. twice daily on days 1 to 5 and days 8 to 12 of a 28-day cycle Each cycle will be repeated after 28 days (from day 1) for a maximum of 4 cycles.

Drug: Ramucirumab; Drug: TAS 102

Interventions

Ramucirumab DRUG

chemotherapy i.v.

Also known as: Cyramza

Ramucirumab plus TAS-102

TAS 102 DRUG

p.o. twice daily

Also known as: Lonsurf

Ramucirumab plus TAS-102

Eligibility Criteria

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

You may qualify if:

• Signed informed consent form.
• Men or women\* ≥ 18 years of age. Patients of reproductive age must be prepared to use a suitable contraceptive method during the study and up to 6 months after the end of treatment. A suitable method of contraception is defined as surgical sterilization (e.g. bilateral fallopian tube ligation, vasectomy), hormonal contraception (implantable, patch, oral), and double barrier methods (each two-fold combination of intrauterine pessary, condom for men, or women with spermicidal gel, diaphragm, contraceptive sponge, cervical cap). Women of child-bearing potential must have a negative pregnancy test within the last 7 days prior to the start of study therapy.
• \*There is no data that indicates a specific gender distribution. Therefore, patients are included regardless of their gender.
• Histologically proven adenocarcinoma of the stomach, including adenocarcinoma of the gastroesophageal junction (note: previous histological assessment during disease history of patient sufficient, current biopsy during screening for this trial is not mandatory)
• Documented, objective, radiological or clinical progression of the disease during or within 4-6 weeks after the last dose of a ramucirumab based second-line therapy (ramucirumab monotherapy or a combination of ramucirumab + paclitaxel, respectively ramucirumab + FOLFIRI).
• Measurable or non-measurable but evaluable disease.
• ECOG Performance status 0-2.
• Life expectancy \> 8 weeks.
• Appropriate haematological, hepatic and renal function:
• Absolute number of neutrophils (ANC) ≥ 1.5 x 10\^9/L
• Platelets ≥ 100 x 10\^9/L
• Hemoglobin ≥ 9 g/dL (5.58 mmol/L)
• Total bilirubin ≤ 1.5 times the upper limit of normal (UNL)
• AST (SGOT) and ALT (SGPT) ≤ 2.5 x UNL without existing liver metastases, or ≤ 5 x UNL in the presence of liver metastases; AP ≤ 5 x UNL
• Serum creatinine ≤ 1.5 x UNL or creatinine clearance (measured by 24h urine) ≥ 40 mL / min (i.e. if the serum creatinine level is \> 1.5 x UNL, then a 24h urine test must be performed to check the creatinine clearance to be determined). Protein level in urine ≤ 1+ by dipstick analysis or routine urine measurement (if the dipstick analysis or the routine test ≥ 2+, a subsequent 24h urine protein measurement must show a value of \< 1000mg of protein within 24h of participation to ensure the study.

You may not qualify if:

• Presence of tumors other than adenocarcinomas (e.g., leiomyosarcoma, lymphoma) or a secondary tumor other than squamous or basal cell carcinomas of the skin or in situ carcinomas of the cervix which have been effectively treated. The sponsor decides to include patients who have received curative treatment and have been disease-free for at least 5 years.
• Squamous cell carcinoma of the stomach or gastroesophageal junction.
• Simultaneous, ongoing, systemic immunotherapy, chemotherapy, or hormone therapy not described in the study protocol.
• Simultaneous treatment with a different anti-cancer therapy other than that provided for in the study (excluding palliative radiotherapy for symptom control).
• 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
• The patient has undergone major surgery within the last 28 days prior to the start of study-specific therapy or has undergone minor surgery within the last 7 days prior to the start of study therapy. The patient had subcutaneous venous access within the last 7 days prior to the start of the study-specific therapy. The patient plans to undergo major surgery while participating in the clinical trial.
• Gastrointestinal bleeding grade 3-4 within the last 3 months prior to enrollment in the study.
• History of deep vein thrombosis (DVT), pulmonary embolism (PE), or any other clinically important thromboembolic event during the last 3 months prior to the start of study-specific therapy (thrombosis caused by venous ports, catheters, or superficial venous thrombosis are not considered "clinically meaningful").
• Stage B cirrhosis according to Child-Pugh criteria (or worse) or cirrhosis (of any grade) with a history of hepatic encephalopathy or clinically significant ascites resulting from cirrhosis. Clinically significant ascites is defined as ascites resulting from cirrhosis requiring diuretics or paracentesis.
• Known brain or leptomeningeal metastases.
• Known allergic / hypersensitive reactions to at least one of the treatment components.
• Other serious illnesses or medical ailments within the last 12 months prior to the start of the study.
• Any arterial thromboembolic event which includes, but is not limited to, the following: myocardial infarction, transient ischemic attack, cerebrovascular insult, unstable angina within the last 6 months prior to the initiation of study therapy.
• Uncontrolled or under-adjusted hypertension (\> 160 mmHg systolic or \> 100 mmHg diastolic hypertension for more than 4 weeks) despite standard medical treatment.
• Presence of an active, uncontrollable infection.

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead

Study Sites (5)

Institute for Clinical Cancer Research Krankenhaus Nordwest

Frankfurt, 60488, Germany

Location

Hamburg Hämatologisch-Onkologische Praxis Eppendorf-Facharztzentrum Eppendorf

Hamburg, 20246, Germany

Location

Tagestherapiezentrum am ITM Universitätsmedizin Mannheim

Mannheim, 68167, Germany

Location

Technische Universität München Klinikum Rechts der Isar

München, 81675, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Related Publications (1)

• Goetze TO, Stein A, Lorenzen S, Habibzada T, Goekkurt E, Herhaus P, Loose M, Sookthai D, Brulin T, Ihrig K, Pauligk C, Al-Batran SE. Ramucirumab beyond progression plus TAS-102 in patients with advanced or metastatic esophagogastric adenocarcinoma, after treatment failure on a ramucirumab-based therapy. Int J Cancer. 2023 Nov 15;153(10):1726-1733. doi: 10.1002/ijc.34652. Epub 2023 Jul 16.

  PMID: 37455496 DERIVED

MeSH Terms

Interventions

Ramucirumab; trifluridine tipiracil drug combination

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Thorsten O Götze, Dr.

  Institute of Clinical Cancer Research UCT - University Cancer Center Frankfurt

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2020
• First Posted: August 18, 2020
• Study Start: October 15, 2020
• Primary Completion: January 13, 2022
• Study Completion: January 20, 2023
• Last Updated: February 10, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (5)