FLOT vs. FLOT/Ramucirumab for Perioperative Therapy of Gastric or GEJ Cancer (RAMSES)

NCT02661971 | Completed Phase 2 DMC

• 1 other identifier: RAMSES/FLOT7
• Study Type: interventional
• Target: 180
• Locations: 2 countries
• Sites: 2

Brief Summary

Previous studies provide a strong theoretical rationale for the conduct of a randomized study evaluating the efficacy and safety of ramucirumab in combination with FLOT in the perioperative treatment of resectable adenocarcinoma of the stomach or GEJ.

Conditions

Stomach Cancer; Gastroesophageal Junction Cancer

Outcome Measures

Primary Outcomes (2)

• Phase II: Rate of pathological complete or subtotal responses (pCR/pSR): assessed according to Becker remission criteria

  3 years

• Phase III: Overall Survival (OS): time from randomization to death of any cause

  Survival rates for the different time points will be determined using the Kaplan-Meier analysis of OS.

  3 years

Secondary Outcomes (9)

• Phase II/III: R0 resection rate: reported descriptively

  75 days

• Phase II/III: Progression Free Survival (PFS): time from randomization until disease progression, disease recurrence after surgery or death of any cause

  3 years

• Phase II: Overall Survival (OS): time from randomization to death of any cause

  3 years

• Phase III: Pathological response rates: assessed according to Becker remission criteria (Becker et al., 2003)

  75 days

• Phase III: Progression Free Survival (PFS): time from randomization until disease progression, disease recurrence after surgery or death of any cause

  3/5 years

Study Arms (2)

FLOT alone

ACTIVE COMPARATOR

Pre-operative therapy with FLOT followed by surgical resection followed by post-operative therapy with FLOT * Docetaxel 50 mg/m², d1 * Oxaliplatin 85 mg/m², d1 * Calciumfolinat 200 mg/m², d1 * 5-Fluorouracil 2600 mg/m², d1

Drug: Docetaxel; Drug: Oxaliplatin; Drug: Calciumfolinat; Drug: 5-Fluorouracil

FLOT + Ramucirumab

EXPERIMENTAL

Pre-operative therapy with FLOT + ramucirumab followed by surgical resection followed by post-operative therapy with FLOT + ramucirumab * Ramucirumab 8mg/kg, d1 * Docetaxel 50 mg/m², d1 * Oxaliplatin 85 mg/m², d1 * Calciumfolinat 200 mg/m², d1 * 5-Fluorouracil 2600 mg/m², d1

Drug: Docetaxel; Drug: Oxaliplatin; Drug: Calciumfolinat; Drug: 5-Fluorouracil; Biological: Ramucirumab

Interventions

Docetaxel DRUG

Docetaxel 50 mg/m², d1

Also known as: TAXOTERE®

FLOT + Ramucirumab; FLOT alone

Oxaliplatin DRUG

Oxaliplatin 85 mg/m², d1

Also known as: ELOXATIN®

FLOT + Ramucirumab; FLOT alone

Calciumfolinat DRUG

Leucovorin 200 mg/m², d1

Also known as: Leucovorin

FLOT + Ramucirumab; FLOT alone

5-Fluorouracil DRUG

5-FU 2600 mg/m², d1

Also known as: 5-FU

FLOT + Ramucirumab; FLOT alone

Ramucirumab BIOLOGICAL

Ramucirumab 8mg/kg, d1

FLOT + Ramucirumab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed, resectable adenocarcinoma of the gastroesophageal junction (AEG/GEJ-type II-III) or the stomach (uT2, uT3, uT4, any N category, M0), or any T N+ M0 patient, with the following specifications:
• Medical and technical operability, according to the techniques described in Chapter 12 Surgical Therapy that are subtotal, total or transhiatal extended gastrectomy (patients planned to receive transthoracic esophagectomy are not eligible for the study)
• Participating sites in PETRARCA study: Negative HER-2 detection (score IHC HER-2 0 or IHC HER-2 1+ ); IHC HER-2 2+ and negative by FISH, SISH or CISH1
• No preceding cytotoxic or targeted therapy
• No prior partial or complete tumor resection
• Female and male patients ≥ 18 and ≤ 70 years. Patients in reproductive age must be willing to use adequate contraception during the study and for 7 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.
• ECOG ≤ 1
• Adequate hematological, hepatic and renal function parameters:
• Leukocytes ≥ 3000/mm³, platelets ≥ 100,000/mm³, neutrophil count (ANC) ≥1000/µL, hemoglobin ≥9 g/dL (5.58 mmol/L),
• 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 receiving warfarin/phenprocoumon must be switched to low molecular weight heparin and have achieved stable coagulation profile prior to randomization.
• Serum creatinine ≤ 1.5 x upper limit of normal
• 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).
• Bilirubin ≤ 1.5 x upper limit of normal, AST and ALT ≤ 3.0 x upper limit of normal, alkaline phosphatase ≤ 6 x upper limit of normal
• Patient able and willing to provide written informed consent and to comply with the study protocol and with the planned surgical procedures

You may not qualify if:

• Known hypersensitivity against ramucirumab, 5-FU, leucovorin, oxaliplatin, or docetaxel
• Other known contraindications against ramucirumab, 5-FU, leucovorin, oxaliplatin, or docetaxel
• Patients with esophageal cancer and those with adenocarcinoma of GEJ type I and all patients who are planned to have transthoracic esophagectomy.
• Clinically significant active coronary heart disease, cardiomyopathy or congestive heart failure, peripheral artery occlusive disease (PAOD, German pAVK), or any history of aortic aneurysm
• Any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina.
• Uncontrolled or poorly-controlled hypertension (\>160 mmHg systolic or \> 100 mmHg diastolic for \>4 weeks) despite standard medical management.
• Clinically significant valvular defect
• Past or current history of other malignancies not curatively treated and without evidence of disease for more than 5 years, except for curatively treated basal cell carcinoma of the skin and in situ carcinoma of the cervix
• Criteria of unresectability, e.g.:
• Radiologically documented evidence of major blood vessel invasion or encasement by cancer.
• Patients with involved retroperitoneal (e.g. para-aortal, paracaval or interaortocaval lymph nodes) or mesenterial lymph nodes (distant metastases!)
• Known brain metastases
• Other severe internal disease or acute infection
• Peripheral polyneuropathy ≥ NCI Grade II
• Chronic inflammatory bowel disease

Sponsors & Collaborators

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

Study Sites (2)

Institute for Clinical Cancer Research Krankenhaus Nordwest

Frankfurt, 60488, Germany

Location

Università degli studi della Campania "Luigi Vanvitelli"

Napoli, Campania, Italy

Location

Related Publications (1)

• Goetze TO, Hofheinz RD, Gaiser T, Schmalenberg H, Strumberg D, Goekkurt E, Angermeier S, Zander T, Kopp HG, Pink D, Siegler G, Schenk M, de Vita F, Galizia G, Maiello E, Bechstein WO, Elshafei M, Loose M, Sookthai D, Brulin T, Pauligk C, Homann N, Al-Batran SE. Perioperative FLOT plus ramucirumab for resectable esophagogastric adenocarcinoma: A randomized phase II/III trial of the German AIO and Italian GOIM. Int J Cancer. 2023 Jul 1;153(1):153-163. doi: 10.1002/ijc.34495. Epub 2023 Mar 23.

  PMID: 36883420 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Docetaxel; Oxaliplatin; Leucovorin; Fluorouracil; Ramucirumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Salah-Eddin Al-Batran, Prof. Dr.

  Institute of Clinical Cancer Research (IKF), UCT - University Cancer Center

  PRINCIPAL INVESTIGATOR

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: January 19, 2016
• First Posted: January 25, 2016
• Study Start: June 1, 2016
• Primary Completion: December 1, 2021
• Study Completion: June 20, 2022
• Last Updated: July 11, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); DE (1)