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

• Status: Completed
• Trial end date: 2020-07-17
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest; Krankenhaus Nordwest
• Collaborator: Trium Analysis Online GmbH
• Treatments: Pertuzumab; Trastuzumab

Criteria

Inclusion Criteria:

1. 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

2. No preceding cytotoxic or targeted therapy

3. No prior partial or complete tumor resection

4. Exclusion of the infiltration of any adjacent organs or structures by CT or MRI

5. Exclusion of distant metastasis by CT or MRI of thorax and abdomen, and bone scan (if osseous lesions are suspected due to clinical signs)

6. 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.

7. ECOG ≤ 2

8. Laparoscopic exclusion of peritoneal carcinomatosis, if suspected clinically

9. 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

10. LVEF value > 55 %, as assessed by echocardiography

11. Patient able and willing to provide written informed consent and to comply with the study protocol and with the planned surgical procedures

Exclusion Criteria:

1. Patients with involved retroperitoneal (e.g. para-aortal, paracaval or interaortocaval lymph nodes) or mesenterial lymph nodes (distant metastasis!)

2. Known hypersensitivity against Herceptin, pertuzumab, 5-FU, leucovorin, oxaliplatin, or docetaxel

3. Other known contraindications against Herceptin, pertuzumab, 5-FU, leucovorin, oxaliplatin, or docetaxel

4. Documented history of congestive heart failure of any NYHA, myocardial infarction within the past 6 months before the first dose of study treatment

5. 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)

6. 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

7. Known brain metastases

8. Other severe internal disease or acute infection

9. Peripheral polyneuropathy ≥ NCI Grade II

10. Chronic inflammatory bowel disease

11. Clinically significant active GI bleeding

12. On-treatment participation in another clinical study in the period 30 days prior to inclusion and during the study

13. Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.

14. Patients in a closed institution according to an authority or court decision (AMG § 40, Abs. 1 No. 4)

15. Any other concurrent antineoplastic treatment including irradiation