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Gastric AdenocarcinomaRE-ExPELNCT04517747

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

A study testing Ramucirumab and TAS 102 in people with Gastric Adenocarcinoma and Metastatic Adenocarcinoma of the Gastroesophageal Junction, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 5 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ramucirumab and TAS 102
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
5 sitesGermany
Study dates
15 Oct 2020to 20 Jan 2023
Phase
Interventional
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 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.
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  • 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.
  • Adequate coagulability, as determined by the International Normalized Ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) ≤ 5 seconds above the UNL (unless anti-coagulation therapy has been given). Patients receiving warfarin / phenoprocoumon must be switched to low molecular weight heparin and must have a stable coagulation profile before starting study-specific therapy.
  • Subject is willing and able to comply with the protocol (including contraceptive measures) for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Who cannot join

  • 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.
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  • 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.
  • Chronic inflammatory bowel disease.
  • Active disseminated intravascular coagulation.
  • Any other serious concomitant or medical condition that, in the opinion of the investigator, presents a high risk of complications to the patient or reduces the likelihood of clinical effect.
  • Known dihydropyrimidine dehydrogenase (DPD) deficiency.
  • History of gastrointestinal perforation / fistula (within the last 6 months prior to the start of study-specific therapy) or presence of risk factors favoring perforation.
  • Serious or non-healing wounds, ulcers, or broken bones within the last 28 days prior to the start of study-specific therapy.
  • The patient is pregnant or breast-feeding.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Germany5 sites

  • Institute for Clinical Cancer Research Krankenhaus Nordwest

    Frankfurt, 60488

  • Hamburg Hämatologisch-Onkologische Praxis Eppendorf-Facharztzentrum Eppendorf

    Hamburg, 20246

  • Tagestherapiezentrum am ITM Universitätsmedizin Mannheim

    Mannheim, 68167

  • Technische Universität München Klinikum Rechts der Isar

    München, 81675

  • Universitätsklinikum Ulm

    Ulm, 89081

Other trials in Germany

About this study

Official title: A Pilot Study of Ramucirumab Beyond Progression Plus TAS-102 in Patients With Advanced or Metastatic Adenocarcinoma of the Stomach or the Gastroesophageal Junction, After Treatment Failure on a Ramucirumab Based Therapy

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).

Read the detailed description

This is an interventional, prospective, non-randomized, open-label, multicenter single-arm pilot study of ramucirumab plus TAS-102 in patients with advanced or metastatic adenocarcinoma of the stomach or the gastroesophageal junction, after treatment failure on a ramucirumab based therapy.

A total number of 20 patients will be enrolled. Potential study participants will be assessed for eligibility during one or several screening visits. The patient has to provide a signed informed consent form prior to any study-specific screening evaluations. Once the patient provides a signed informed consent form and eligibility is confirmed (all inclusion/exclusion criteria have been verified), the patient can be enrolled.

All screening procedures must be completed during the 14-day screening period. All patients must have had disease status confirmed as per CT or MRI scan of the tumor(s) within ≤ 4 weeks prior to the first dose. Other screening assessments include blood sampling, performance status (ECOG) and ECG according to clinical routine. Study treatment will be continued until progression or intolerable toxicity, but for a maximum of 4 months. Further treatment after progression will be at the investigator's discretion.

Tumor assessment will be performed according to clinical routine at screening and every 8 weeks (±7 days) during the treatment phase of the study and every 12 weeks (±14 days) during follow-up.

The expected duration of the active study phase (FPI - LPO) is 18 months. The active phase per individual patient is approximately 6 months.

Being tested
Ramucirumab, TAS 102

What participants receive

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

  • RamucirumabDrug

    Also called Cyramza

    chemotherapy i.v.

  • TAS 102Drug

    Also called Lonsurf

    p.o. twice daily

Study groups in NCT04517747
Study groupRoleWhat they receive
Ramucirumab plus TAS-102ExperimentalRamucirumab 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.
Receives: Drug: Ramucirumab; Drug: TAS 102

What is being measured

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

  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

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

Secondary outcomes (9)

  1. Rate of treatment-related AEs and SAE

    Rate of treatment-related AEs and SAEs according to CTCAE v5.0

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

  2. Adverse events for neutropenia

    Rate of grade 3 or worse adverse events for neutropenia

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

  3. Adverse events for anemia

    Rate of grade 3 or worse adverse events for anemia

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

  4. Adverse events for leucopenia

    Rate of grade 3 or worse adverse events for leucopenia

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

  5. Adverse events for thrombocytopenia

    Rate of grade 3 or worse adverse events for thrombocytopenia

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

  6. Abnormal laboratory parameters

    Frequency of abnormal laboratory parameters

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

  7. Progression Free Survival (PFS)

    Progression Free Survival (PFS) according to RECIST 1.1, Progression free survival (PFS) is defined as the time from enrollment to the first documented evidence of disease progression or death. If no information will be available for the evaluation of progression, patients will be censored at the timepoint of last tumor assessment.

    Measured: Progression free survival (PFS) is defined as the time from enrollment to the first documented evidence of disease progression or death; up to 16 months.

  8. Objective Response Rate (ORR)

    Objective response rate is defined as proportion of patients with a best overall response of complete response (CR) or partial response (PR). Tumor response will be evaluated using RECIST 1.1 criteria.

    Measured: defined as the time from enrollment up to 16 months.

  9. Overall survival

    Overall survival

    Measured: Overall survival (OS) is defined as the time from enrollment to the date of death from any cause.; up to 16 months.

Timeline

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

  1. First posted18 Aug 2020
  2. Study start15 Oct 2020
  3. Primary completion13 Jan 2022
  4. Study completion20 Jan 2023

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 N/A
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04517747
Sponsor's protocol ID
RE-ExPEL
Acronym
RE-ExPEL
Status last verified
Feb 2023
First submitted
14 Aug 2020
Last updated
10 Feb 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 37455496

Questions about this trial

What is this clinical trial studying?

A study testing Ramucirumab and TAS 102 in people with Gastric Adenocarcinoma and Metastatic Adenocarcinoma of the Gastroesophageal Junction, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 5 sites 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 17 inclusion and 22 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: finished, as of the sponsor's last update on 10 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites 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.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Tolerability and toxicity: rate of serious adverse events (SAEs) of any cause (time frame: Frist Treatment until 30 days after end of treatment, up to 5 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 NCT04517747, which also lists 1 linked publication.

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 10 Feb 2023.

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