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

NCT03762564 | Completed Phase 2

• 3 other identifiers: RAMOSAIO-STO-02162016-003850-33
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Squamous Cell Carcinoma of the Esophagus

Keywords

Squamous Cell Carcinoma of the Esophagus; Ramucirumab; Paclitaxel

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS) at 6 months

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

  6 months

Secondary Outcomes (6)

• Progression-free survival (PFS)

  Up to 2 years

• Overall survival

  Up to 2 years

• Objective response rate

  Up to 2 years

• Tumor control rate

  Up to 2 years

• Quality of life (QoL)

  Up to 1 year and 30 days

Study Arms (2)

Arm A (Paclitaxel + Ramucirumab)

EXPERIMENTAL

Paclitaxel 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

Drug: Ramucirumab; Drug: Paclitaxel

Arm B (control arm)

ACTIVE COMPARATOR

Paclitaxel 80 mg/m2 as 1 hour intravenous infusion on day 1, 8, 15 qd 28

Drug: Paclitaxel

Interventions

Ramucirumab DRUG

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

Also known as: Cyramza

Arm A (Paclitaxel + Ramucirumab)

Paclitaxel DRUG

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

Arm A (Paclitaxel + Ramucirumab); Arm B (control arm)

Eligibility Criteria

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

You may qualify if:

• 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".
• 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)

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead
• Eli Lilly and Company: collaborator
• Trium Analysis Online GmbH: collaborator

Study Sites (2)

Institute for Clinical Cancer Research Krankenhaus Nordwest

Frankfurt, 60488, Germany

Location

Technische Universität München Klinikum rechts der Isar

München, 81675, Germany

Location

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

Ramucirumab; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Salah-Eddin Al-Batran, Prof. Dr.

  Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2018
• First Posted: December 3, 2018
• Study Start: March 8, 2019
• Primary Completion: July 4, 2022
• Study Completion: November 25, 2022
• Last Updated: December 8, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)