Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
drksid header

  DRKS00010662

Trial Description

start of 1:1-Block title

Title

FLOT vs. FLOT/Herceptin/Pertuzumab for Perioperative Therapy of Adenocarcinoma of the Stomach and Gastroesophageal Junction Expressing HER-2. A Phase II/III Trial of the AIO.

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

PETRARCA

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

[---]*

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

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.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

This is a multicenter, randomized, controlled, open-label study including patients with
locally advanced adenocarcinoma of the stomach and GEJ scheduled to receive perioperative
chemotherapy. According to centrally assessed HER-2 status: Patients with HER-2 positive
tumors will receive FLOT +/- Herceptin / pertuzumab.

The scope of the phase II portion of the trial is to evaluate pathological response rates of
either regimen assessed by a centralized pathology and define safety and tolerability.

Patients with locally advanced esophagogastric adenocarcinoma (i.e. cT2 any N or any T
N-positive) with exclusion of distant metastases will be included in this trial.

Patients will be stratified by age (18-69 vs. ≥ 70), tumor site (GEJ vs. gastric) and
clinical stage (T1/2 vs. 3/4 and N- vs. N+) and randomized 1:1 to receive either FLOT (Arm
A) or FLOT/Herceptin/pertuzumab (Arm B).

Arm A (control group) Patients randomized to Arm A will receive 4 pre-operative treatments
of FLOT (Docetaxel 50 mg/m², iv over 2 h; Oxaliplatin 85 mg/m² in 500 ml G5%, iv over 2h;
Leucovorin 200 mg/m² in 250 ml NaCl 0.9 %, iv over 1 h; 5-FU 2600 mg/m², iv over 24 h) on
d1, d15, d29, d43 of the preoperative treatment phase. Surgery is recommended to occur 4
weeks after last FLOT (4 weeks after d43 = day 71). Patients will receive 4 additional
post-operative treatments of FLOT on d1, d15, d29, and d43 of the post-operative treatment
phase. Post-operative treatment should start 6 to 8 weeks, but at maximum 12 weeks after
surgery.

Arm B (Herceptin/pertuzumab group) Patients randomized to Arm B will receive the FLOT
regimen identical to Arm A as described above in conjunction with three-weekly Herceptin at
8mg/kg initial dose (Day 1, loading dose) followed by subsequent doses of Herceptin at
6mg/kg on d22 and d43 and pertuzumab at 840mg on d1, d22, and d43. Surgery is recommended to
occur 4 weeks after last FLOT/Herceptin/pertuzumab dose (4 weeks after d43 = day 71).
Patients will receive 3 additional doses of Herceptin and pertuzumab on d1, d22, and d43 of
the post-operative treatment phase, together with the postoperative chemotherapy. Moreover,
patients will receive 11 additional doses of Herceptin and pertuzumab after the end of
post-operative FLOT.

In both of the arms, tumor assessments (CT or MRI) are performed before randomization and
prior to surgery and then every 3 months thereafter until progression/relapse, death or end
of follow-up.

During treatment, clinical visits (blood cell counts, detection of toxicity) occur prior to
every treatment dose. Safety of FLOT/Herceptin/pertuzumab will be monitored continuously by
careful monitoring of all adverse events (AEs) and serious adverse events (SAEs) reported.

end of 1:1-Block scientific synopsis
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00010662
  •   2016/06/17
  •   2015/10/19
  •   yes
  •   [---]*
  •   [---]*
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  •   NCT02581462  (ClinicalTrials.gov)
  •   ML29452/PETRARCA/FLOT6  (Krankenhaus Nordwest)
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   Stomach Cancer
  •   Gastroesophageal Junction Cancer
  •   C16 -  Malignant neoplasm of stomach
  •   C16.0 -  Malignant neoplasm: Cardia
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   Drug: FLOT alone
  •   Biological: FLOT + Herceptin/Pertuzumab
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   [---]*
  •   Treatment
  •   Parallel
  •   II-III
  •   [---]*
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

- PhaseII: Rate of pathological complete response; time frame: 3 years
- Phase III: Median Progression Free Survival; time frame: 5 years

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

- Phase II/III: R0 resection rate; time frame: 75 days
- Phase II: Median Progression Free Survival (PFS); time frame: 3 years
- Phase II/III: Median Overall Survival; time frame: 3/5 years
- Phase II: PK Analysis; time frame: 3 years
- Phase II/III: Subgroup analyses: pathological response according to HER-2 status HER-2 IHC 3+ vs. other cases; time frame: 3/5 years
- Phase II/III: Subgroup analyses: PFS according to HER-2 status HER-2 IHC 3+ vs. other cases; time frame: 3/5 years
- Phase II/III: Subgroup analyses: OS according to HER-2 status HER-2 IHC 3+ vs. other cases; time frame: 3/5 years
- Phase III: Pathological Response Rates; time frame: 5 years
- Phase III: PFS rates; time frame: 3 and 5 years
- Phase III: OS rates; time frame: 3 and 5 years
- Phase III: Median OS; time frame: 5 years

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Germany
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  •  
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   [---]*
  •   2016/05/31
  •   404
  •   [---]*
  •   National
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   99   Years
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional 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

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

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

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • Krankenhaus Nordwest
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address other
    • Trium Analysis Online GmbH
    end of 1:1-Block address other
    start of 1:1-Block address contact other
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact other
  • start of 1:1-Block address scientific-contact
    • Universitätsmedizin Mannheim
    • Ralf-Dieter Hofheinz, Prof. Dr. 
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Salah-Eddin Al-Batran, Prof. Dr. 
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting ongoing
  •   [---]*
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

  • [---]*
end of 1:n-Block publications
The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   2
  •   2016/06/08
* This entry means the parameter is not applicable or has not been set.