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Squamous Cell Carcinoma of the EsophagusPhase 2RAMOSNCT03762564

Study With Paclitaxel +/- Ramucirumab in Patients With Squamous-cell Carcinoma of the Esophagus After Prior Therapy

A Phase 2 study testing Ramucirumab and Paclitaxel in people with Squamous Cell Carcinoma of the Esophagus, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 2 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

This is a multicenter, randomized, controlled, open-label phase II study including patients with squamous-cell carcinoma of the esophagus, refractory or intolerant to combination therapy with Fluoropyrimidine and Platinum-based drugs. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Squamous Cell Carcinoma of the Esophagus
What is being tested?
Ramucirumab and Paclitaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
2 sitesGermany
Study dates
8 Mar 2019to 25 Nov 2022
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; Patients in reproductive age must be willing to use adequate contraception during the study and for 6 months after the end of ramucirumab treatment (Appropriate contraception is defined as surgical sterilization (e.g., bilateral tubal ligation, vasectomy), hormonal contraception (implantable, patch, oral), and double-barrier methods (any double combination of: IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap)). Female patients with childbearing potential need to have a negative pregnancy test within 7 days before study start.
  • There are no data that indicate special gender distribution. Therefore, patients will be enrolled in the study gender-independently.
  • Histologically proven squamous cell carcinoma of the esophagus
  • Adult patients with metastatic or locally advanced squamous-cell carcinoma of the esophagus, not amenable to potentially curative resection, who are refractory to or intolerant of prior platinum/fluoropyrimidine combination therapy. The definition of refractory should be defined as follows:
  • Patients whose PD or recurrence was confirmed by imaging during their initial chemotherapy (including chemoradiation) or within 8 weeks after the last dose of chemotherapy will be assessed as "refractory".
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  • Patients after radical resection in conjunction with chemotherapy, including neoadjuvant/adjuvant therapy and chemoradiation, whose recurrence was confirmed by imaging within 24 weeks after the last dose of chemotherapy, will be determined "refractory".
  • Measurable or non-measurable but evaluable disease determined using guidelines in RECIST 1.1 as confirmed within 28 days before randomization
  • ECOG performance status 0-1;
  • Life expectancy > 12 weeks;
  • Adequate hematological, hepatic and renal functions:
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L;
  • Platelets ≥ 100 x 109/L;
  • Hemoglobin ≥9 g/dL (5.58 mmol/L
  • Total bilirubin ≤ 1.5 times the upper normal limit (UNL)
  • AST (SGOT) and ALT (SGPT) ≤ 2.5 x UNL in absence of liver metastases, or ≤ 5 x UNL in presence of liver metastases; AP ≤ 5 x UNL
  • Serum creatinine ≤ 1.5 x upper limit of normal, or creatinine clearance (measured via 24-hour urine collection) ≥40 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)
  • Urinary protein ≤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).
  • Adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy). Patients on full-dose anticoagulation must be on a stable dose (minimum duration 14 days) of oral anticoagulant or low molecular weight heparin (LMWH). Patients receiving warfarin/ phenprocoumon must be switched to low molecular weight heparin and have an INR ≤3.0 prior to first dose of protocol therapy. 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).
  • Ability to comply with scheduled assessments and with management of toxicities

Who cannot join

  • Other tumor type than squamous carcinoma (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 and disease-free for at least 5 years will be discussed with the sponsor before inclusion.
  • Patients with significant malnutrition who receive intravenous hyperalimentation or require continuous infusion therapy with hospitalization.
  • Patients with apparent tumor invasion on organs located adjacent to the esophageal disease. Patients will be excluded if they are receiving stent therapy in esophagus or respiratory tract.
  • Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy not indicated in the study protocol.
  • Previous therapy with paclitaxeI
  • Current treatment with any anti-cancer therapy ≤ 2 weeks prior to study treatment start, unless rapidly progressing disease is measured
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  • Concurrent treatment with any other anti-cancer therapy
  • Previous exposure to a VEGF or VEGFR inhibitor or any antiangiogenic agent, or prior enrolment in this study
  • Patient has undergone major surgery within 28 days prior to first dose of protocol therapy, or minor surgery/subcutaneous venous access device placement within 7 days prior to first dose of protocol therapy. The patient has elective or planned major surgery to be performed during the course of the clinical trial.
  • 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 allergic/ hypersensitivity reaction to any of the components of the treatment.
  • Other serious illness or medical conditions within the last 12 months prior to study drug administration.
  • Any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to first dose of protocol.
  • The patient has uncontrolled or poorly-controlled hypertension (>160 mmHg systolic or > 100 mmHg diastolic for >4 weeks) despite standard medical management.
  • Active uncontrolled infection.
  • Active disseminated intravascular coagulation.
  • Any other serious concomitant disease or medical condition that in the judgment of the investigator renders the subject at high risk of treatment complication or reduced the probability of assessing clinical effect
  • Prior history of GI perforation/fistula (within 6 months of first dose of protocol therapy) or risk factors for perforation.
  • Serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy.
  • 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.
  • Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to treatment start.
  • Known drug abuse/ alcohol abuse.
  • Lack of resolution of all toxic effects (excluding alopecia) of prior chemotherapy, prior radiotherapy or surgical procedure to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade < 1. Note: Neuropathy due to prior chemotherapy is allowed if not > NCI Grade II according to CTCAE version 4.0.
  • Subject pregnant or breast feeding, or planning to become pregnant within 6 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 6 months (male or female) after the end of treatment.
  • Patients with a psychiatric illness or patients imprisoned or working in the institution of the treating physician.

Trial locations and contacts

2 sites in 1 country.

Germany2 sites

  • Institute for Clinical Cancer Research Krankenhaus Nordwest

    Frankfurt, 60488

  • Technische Universität München Klinikum rechts der Isar

    München, 81675

Other trials in Germany

About this study

Official title: A Randomized, Multicenter Open Label Phase II Trial of Paclitaxel + Ramucirumab Versus Paclitaxel Alone in Patients With Squamous-cell Carcinoma of the Esophagus, Refractory or Intolerant to Combination Therapy With Fluoropyrimidine and Platinum-based Drugs - The RAMOS STUDY

This is a multicenter, randomized, controlled, open-label phase II study including patients with squamous-cell carcinoma of the esophagus, refractory or intolerant to combination therapy with Fluoropyrimidine and Platinum-based drugs.

Read the detailed description

This is a phase II, randomized, open-label multi-center study comparing treatment of paclitaxel plus ramucirumab with paclitaxel monotherapy in patients with advanced squamous-cell carcinoma (SCC) of the esophagus.

Adult patients with histologically or cytologically confirmed advanced squamous-cell carcinoma of the esophagus and refractory or intolerant to combination therapy with Fluoropyrimidine and Platinum-based drugs will be enrolled in the study.

A total number of 186 patients will be enrolled (Randomization 1:1). 93 patients will be treated with paclitaxel + ramucirumab (Arm A) and 93 with paclitaxel (Arm B).

Randomization will be stratified by time of progression during or after end of first-line therapy (≤3 months vs. >3 months).

The primary objective is to compare overall survival (OS) after 6 months in patients with squamous-cell carcinoma of the esophagus, refractory or intolerant to combination therapy with Fluoropyrimidine and Platinum-based drugs receiving paclitaxel with ramucirumab versus paclitaxel alone in the intent-to-treat population (ITT). OS is defined as the time from randomization to death from any cause.

Patients in Arm A (investigational arm) receive Paclitaxel 80 mg/m2 on day 1, 8, 15 plus Ramucirumab 8 mg/kg i.v. infusion on day 1 and 15 every 4 weeks. Patients in Arm B (control arm) receive Paclitaxel 80 mg/m2 on day 1, 8, 15 every 4 weeks. Study treatment will be continued until progression or intolerable toxicity, but for a maximum of 1 year.

Tumor assessment will be performed according to clinical routine at screening / baseline and every 8 weeks.

After discontinuation of study medication, patients will be followed for up to 1 year. Tumor assessments per CT or MRI will be performed every 2 months for 6 months or until documentation of disease progression. Follow-up for survival will be done and documented every 2 months for the 1 year follow-up period after end of treatment.

During treatment, clinical visits (blood cell counts, detection of toxicity) will be performed prior to every treatment dose. Safety of paclitaxel +/- ramucirumab will be monitored continuously by careful monitoring of all adverse events (AEs) and serious adverse events (SAEs) reported. Prior to the start of each cycle and at the 30-day safety follow-up visit Quality of life (QoL) will be assessed using the European Organization for Research and treatment of Cancer Quality of Life Questionnaire-C30 (EORTC-QLQ-C30).

Being tested
Ramucirumab, Paclitaxel
Keywords
Squamous Cell Carcinoma of the Esophagus, Ramucirumab, Paclitaxel
Medical subject headings
Esophageal Squamous Cell Carcinoma

What participants receive

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

  • RamucirumabDrug

    Also called Cyramza

    Ramucirumab 8 mg/kg i.v. infusion on day 1 and 15

  • PaclitaxelDrug

    Paclitaxel 80 mg/m2 on day 1, 8, 15

Study groups in NCT03762564
Study groupRoleWhat they receive
Arm A (Paclitaxel + Ramucirumab)ExperimentalPaclitaxel 80 mg/m2 as 1 hour intravenous infusion on day 1, 8, 15 plus Ramucirumab 8 mg/kg as 1 hour intravenous infusion on day 1 and 15 qd 28
Receives: Drug: Ramucirumab; Drug: Paclitaxel
Arm B (control arm)Active comparatorPaclitaxel 80 mg/m2 as 1 hour intravenous infusion on day 1, 8, 15 qd 28
Receives: Drug: Paclitaxel

What is being measured

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

  1. Overall survival (OS) at 6 months

    OS rate at 6 months, defined as patients who are alive after at 6 months

    Measured: 6 months

Secondary outcomes (6)

  1. Progression-free survival (PFS)

    PFS, defined as the time from randomization to the first occurrence of progression, as determined by the investigator using CT criteria, or death from any cause

    Measured: Up to 2 years

  2. Overall survival

    Overall survival according to Kaplan-Meier

    Measured: Up to 2 years

  3. Objective response rate

    Objective response rate defined as the proportion of patients with complete or partial remission according to RECIST 1.1

    Measured: Up to 2 years

  4. Tumor control rate

    Tumor control rate defined as the proportion of patients with complete or partial remission or stable disease according to RECIST 1.1

    Measured: Up to 2 years

  5. Quality of life (QoL)

    Quality of life (QoL) as measured by EORTC-QLQ-C30 at d1 of each cycle, on EOT (end of treatment) and 30 days after EOT.

    Measured: Up to 1 year and 30 days

  6. Incidence and severity of adverse events

    incidence and severity of adverse events according to CTCAE (Common Terminology Criteria for Adverse Events) Version 4 criteria as assessed at day 1, 8 and 15 of every cycle during treatment for a maximum of 12 months and until 30 days after the last dose of study drug

    Measured: Up to 1 year and 30 days

Timeline

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

  1. First posted3 Dec 2018
  2. Study start8 Mar 2019
  3. Primary completion4 Jul 2022
  4. Study completion25 Nov 2022

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03762564
Sponsor's protocol ID
RAMOS
Other IDs
AIO-STO-0216, 2016-003850-33, 2016
Acronym
RAMOS
Status last verified
Dec 2022
First submitted
27 Nov 2018
Last updated
8 Dec 2022
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: No IPD will be shared

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ramucirumab and Paclitaxel in people with Squamous Cell Carcinoma of the Esophagus, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 2 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 20 inclusion and 29 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 8 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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.

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?

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?

Overall survival (OS) 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 NCT03762564.

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 8 Dec 2022.

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