FLOT vs. FLOT/Herceptin/Pertuzumab for Perioperative Therapy of HER-2 Expressing Gastric or GEJ Cancer

NCT02581462 | Completed Phase 2 DMC

• 1 other identifier: ML29452/PETRARCA/FLOT6
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

Brief Summary

Previous studies provide a strong theoretical rationale for the conduct of a randomized study evaluating the efficacy and safety of Herceptin and pertuzumab in combination with FLOT in the perioperative treatment of resectable HER-2 positive adenocarcinoma of the stomach or GEJ.

Conditions

Stomach Cancer; Gastroesophageal Junction Cancer

Outcome Measures

Primary Outcomes (2)

• PhaseII: Rate of pathological complete response

  3 years

• Phase III: Median Progression Free Survival

  5 years

Secondary Outcomes (11)

• Phase II/III: R0 resection rate

  75 days

• Phase II: Median Progression Free Survival (PFS)

  3 years

• Phase II/III: Median Overall Survival

  3/5 years

• Phase II: PK Analysis

  3 years

• Phase II/III: Subgroup analyses: pathological response according to HER-2 status HER-2 IHC 3+ vs. other cases

  3/5 years

Study Arms (2)

FLOT alone

EXPERIMENTAL

Pre-operative therapy with FLOT followed by surgical resection followed by post-operative therapy with FLOT

Drug: FLOT alone

FLOT + Herceptin/Pertuzumab

EXPERIMENTAL

Pre-operative therapy with FLOT + Herceptin/Pertuzumab followed by surgical resection followed by post-operative therapy with FLOT + Herceptin/Pertuzumab

Biological: FLOT + Herceptin/Pertuzumab

Interventions

FLOT alone DRUG

Pre-operative therapy: * Docetaxel 50 mg/m², d1, d15, d29, d43 * Oxaliplatin 85 mg/m², d1, d15, d29, d43 * Leucovorin 200 mg/m², d1, d15, d29, d43 (can be replaced by sodium folinate according to local guidelines) * 5-FU 2600 mg/m², d1, d15, d29, d43 Surgery is recommended to be scheduled 4 weeks after d43. Post-operative therapy (start 6 to 8 weeks after surgery): * Docetaxel 50 mg/m², d1, d15, d29, d43 * Oxaliplatin 85 mg/m², d1, d15, d29, d43 * Leucovorin 200 mg/m², d1, d15, d29, d43 (can be replaced by sodium folinate according to local guidelines) * 5-FU 2600 mg/m², d1, d15, d29, d43

FLOT alone

FLOT + Herceptin/Pertuzumab BIOLOGICAL

Pre-operative therapy: * Herceptin 8/6 mg/kg, d1, d22, d43 * Pertuzumab 840 mg, d1, d22, d43 * Docetaxel 50 mg/m², d1, d15, d29, d43 * Oxaliplatin 85 mg/m², d1, d15, d29, d43 * Leucovorin 200 mg/m², d1, d15, d29, d43 (can be replaced by sodium folinate according to local guidelines) * 5-FU 2600 mg/m², d1, d15, d29, d43 Surgery is recommended to be scheduled 4 weeks after d43. Post-operative therapy (start 6 to 8 weeks after surgery): * Herceptin 8/6 mg/kg, d1, d22, d43 * Pertuzumab 840 mg, d1, d22, d43 * Docetaxel 50 mg/m², d1, d15, d29, d43 * Oxaliplatin 85 mg/m², d1, d15, d29, d43 * Leucovorin 200 mg/m², d1, d15, d29, d43 (can be replaced by sodium folinate according to local guidelines) * 5-FU 2600 mg/m², d1, d15, d29, d43.

FLOT + Herceptin/Pertuzumab

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed adenocarcinoma of the GEJ (type I-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
• Centralized detection of either an adenocarcinoma with HER-2 3+ (IHC) or HER-2 2+ (IHC) with amplification proven by FISH, SISH or CISH
• No preceding cytotoxic or targeted therapy
• No prior partial or complete tumor resection
• Female and male patients ≥ 18 years. Patients in reproductive age must be willing to use adequate contraception during the study and for 7 months after the end of pertuzumab and Herceptin 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 ≤ 2
• Adequate haematological, hepatic and renal function parameters:
• Leukocytes ≥ 3.000/mm³, platelets ≥ 100.000/mm3
• Serum creatinine ≤ 1.5 x upper limit of normal, or GFR \> 40 ml/min
• Bilirubin ≤ 1.5 x upper limit of normal, AST and ALT ≤ 3.5 x upper limit of normal, alkaline phosphatase ≤ 6 x upper limit of normal
• LVEF value \> 55 %, as assessed by echocardiography
• 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:

• Patients with involved retroperitoneal (e.g. para-aortal, paracaval or interaortocaval lymph nodes) or mesenterial lymph nodes (distant metastasis!)
• Known hypersensitivity against Herceptin, pertuzumab, 5-FU, leucovorin, oxaliplatin, or docetaxel
• Other known contraindications against Herceptin, pertuzumab, 5-FU, leucovorin, oxaliplatin, or docetaxel
• Documented history of congestive heart failure of any NYHA, myocardial infarction within the past 6 months before the first dose of study treatment
• Clinically significant valvular defect , history of poorly controlled arterial hypertension (systolic blood pressure \> 180 mmHG or diastolic blood pressure \> 100 mmHg) or uncontrollable high-risk cardiac arrhythmia (i.e tachycardia with a heart rate \> 100/min at rest), significant ventricular arrhythmia (ventricular tachycardia) or higher grade atrioventricular-block (second degree AV-block Type 2 (Mobitz2) or third degree AV-block)
• 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
• Known brain metastases
• Other severe internal disease or acute infection
• Peripheral polyneuropathy ≥ NCI Grade II
• Chronic inflammatory bowel disease
• Clinically significant active GI bleeding
• Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.
• Patients in a closed institution according to an authority or court decision (AMG § 40, Abs. 1 No. 4)
• Any other concurrent antineoplastic treatment including irradiation

Sponsors & Collaborators

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

Study Sites (1)

Institute for Clinical Cancer Research Krankenhaus Nordwest

Frankfurt, 60488, Germany

Location

Related Publications (1)

• Hofheinz RD, Merx K, Haag GM, Springfeld C, Ettrich T, Borchert K, Kretzschmar A, Teschendorf C, Siegler G, Ebert MP, Goekkurt E, Mahlberg R, Homann N, Pink D, Bechstein W, Reichardt P, Flach H, Gaiser T, Battmann A, Oduncu FS, Loose M, Sookthai D, Pauligk C, Goetze TO, Al-Batran SE. FLOT Versus FLOT/Trastuzumab/Pertuzumab Perioperative Therapy of Human Epidermal Growth Factor Receptor 2-Positive Resectable Esophagogastric Adenocarcinoma: A Randomized Phase II Trial of the AIO EGA Study Group. J Clin Oncol. 2022 Nov 10;40(32):3750-3761. doi: 10.1200/JCO.22.00380. Epub 2022 Jun 16.

  PMID: 35709415 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Trastuzumab; pertuzumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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.

  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: October 19, 2015
• First Posted: October 21, 2015
• Study Start: June 1, 2016
• Primary Completion: July 17, 2020
• Study Completion: July 17, 2020
• Last Updated: August 11, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)