A RANDOMIZED, MULTICENTER, ADAPTIVE PHASE II/III STUDY TO EVALUATE THE EFFICACY AND SAFETY OF TRASTUZUMAB EMTANSINE (T-DM1) VERSUS TAXANE (DOCETAXEL OR PACLITAXEL) IN PATIENTS WITH PREVIOUSLY TREATED LOCALLY ADVANCED OR METASTATIC HER2-POSITIVE GASTRIC CANCER, INCLUDING ADENOCARCINOMA OF THE GASTROESOPHAGEAL JUNCTIO

Not Applicable

• Registration Number: PER-118-12
• Lead Sponsor: F. HOFFMANN-LA ROCHE LTD.,

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-02-05
• Last Update Posted: 4 September 2023

Recruitment & Eligibility

• Sex: Not specified
• Target Recruitment: 1

Inclusion Criteria

1. PATIENTS MUST HAVE A HISTORY OF HISTOLOGICALLY OR CYTOLOGICALLY CONFIRMED AGC, DEFINED AS UNRESECTABLE AND LOCALLY ADVANCED OR METASTATIC GASTRIC CANCER, INCLUDING ADENOCARCINOMA OF THE GEJ, AND MUST HAVE EXPERIENCED DOCUMENTED OBJECTIVE RADIOGRAPHIC OR PATHOLOGIC DISEASE PROGRESSION DURING OR AFTER FIRST-LINE THERAPY FOR THEIR DISEASE.
2. HER2-POSITIVE TUMOR (PRIMARY TUMOR OR METASTATIC LESION), DEFINED AS EITHER IHC 3+ ALONE OR IHC 2+ IN COMBINATION WITH ISH+, PROSPECTIVELY CONFIRMED BY A SPONSOR-DESIGNATED CENTRAL LABORATORY PRIOR TO ENROLLMENT. ISH POSITIVITY IS DEFINED AS A RATIO OF ≥ 2.0 FOR THE NUMBER OF HER2 GENE COPIES TO THE NUMBER OF SIGNALS FOR CEP17.
A) ARCHIVAL TUMOR SAMPLES OBTAINED FROM PRIMARY OR METASTATIC SITES (ORIGINAL DIAGNOSTIC SPECIMENS) ARE PREFERRED.
B) THE BLOCK OR SLIDES SHOULD INCLUDE A REPRESENTATIVE PART OF THE TUMOR WITH AN INVASIVE TUMOR AREA FOR CENTRAL CONFIRMATION OF HER2 STATUS.
I. IF FFPE TISSUE BLOCKS (OR PARTIAL BLOCK) ARE UNAVAILABLE DUE TO COUNTRY OR
SITE REGULATIONS, A MINIMUM OF 8 FRESHLY CUT UNSTAINED SLIDES MUST BE AVAILABLE
FOR CENTRAL CONFIRMATION OF HER2 STATUS AND UP TO AN ADDITIONAL 5 SLIDES FOR MANDATORY BIOMARKER RESEARCH, IF SUFFICIENT TISSUE IS AVAILABLE.
3. FIRST-LINE THERAPY FOR AGO, INCLUDING ADENOCARCINOMA OF THE GEJ, MUST HAVE INCLUDED A COMBINATION OF AT LEAST A PLATINUM (E.G., CISPLATIN, CARBOPLATIN, OR OXALIPLATIN) AND A FLUOROPYRIMIDINE (E.G., 5-FU, CAPECITABINE, OR S-1) GIVEN CONCURRENTLY; PRIOR THERAPY

Exclusion Criteria

1. AN INTERVAL SHORTER THAN 21 DAYS FROM THE LAST DOSE OF CHEMOTHERAPY OR HER2-DIRECTED THERAPY UNTIL THE TIME OF RANDOMIZATION
2. PRIOR TREATMENT WITH TRASTUZUMAB EMTANSINE, DOCETAXEL, OR PACLITAXEL EITHER AS SINGLE AGENTS OR AS PART OF A TREATMENT REGIMEN. PRIOR TREATMENT WITH TRASTUZUMAB, LAPATINIB, OR PERTUZUMAB IS ALLOWED.
3. TREATMENT WITH ANY ANTICANCER INVESTIGATIONAL DRUG WITHIN 21 DAYS OF THE FIRST STUDY TREATMENT ADMINISTRATION
4. MORE THAN ONE PRIOR LINE OF THERAPY FOR AGC
5. HISTORY OF OTHER MALIGNANCY WITHIN THE PREVIOUS 5 YEARS EXCEPT FOR APPROPRIATELY TREATED CARCINOMA IN SITU OF THE CERVIX, NON-MELANOMA SKIN CARCINOMA, STAGE I UTERINE CANCER, OR OTHER MALIGNANCIES WITH AN EXPECTED CURATIVE OUTCOME
6. BRAIN METASTASES THAT ARE UNTREATED OR SYMPTOMATIC OR REQUIRE ANY RADIATION, SURGERY, OR STEROID THERAPY TO CONTROL SYMPTOMS FROM BRAIN METASTASES WITHIN 1 MONTH OF RANDOMIZATION
7. PERIPHERAL NEUROPATHY GRADE ≥ 2 PER NCI CTCAE, V4.03
8. HISTORY OF EXPOSURE TO THE FOLLOWING CUMULATIVE DOSES OF ANTHRACYCLINES:
A) DOXORUBICIN >500 MG/M²
B) EPIRUBICIN >720 MG/M²
c) IF ANOTHER ANTHRACYCLINE OR MORE THAN ONE ANTHRACYCLINE HAS BEEN USED, THEN THE CUMULATIVE DOSE MUST NOT EXCEED THE EQUIVALENT OF 500 MG/M² DOXORUBICIN.

Study & Design

• Study Type: Interventional
• Study Design: Not specified