Clinical trial · Interventional
A Study of Pertuzumab in Combination With Trastuzumab and Chemotherapy in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Gastroesophageal Junction or Gastric Cancer
A Double-Blind, Placebo-Controlled, Randomized, Multicenter Phase III Study Evaluating the Efficacy and Safety of Pertuzumab in Combination With Trastuzumab and Chemotherapy in Patients With HER2-Positive Metastatic Gastroesophageal Junction and Gastric Cancer
NCT01774786CI-TRIAL-00049196JACOBcompletedPhase 3Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This double-blind, placebo-controlled, randomized, multicenter, international, parallel arm study will evaluate the efficacy and safety of pertuzumab in combination with trastuzumab, fluoropyrimidine and cisplatin as first-line treatment in participants with HER2-positive metastatic gastroesophageal junction (GEJ) or gastric cancer (GC). Participants will be randomized to receive pertuzumab 840 milligrams (mg) or placebo intravenously every 3 weeks (q3w) in combination with trastuzumab (initial dose of 8 milligrams per kilogram \[mg/kg\] intravenously \[IV\] followed by 6 mg/kg IV q3w) and cisplatin and fluoropyrimidine (capecitabine or 5-fluorouracil) for the first 6 treatment cycles. Participants will continue to receive pertuzumab or placebo and trastuzumab until disease progression occurrence of unacceptable toxicity or withdrawal from the study for another reason.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Gastric Cancer | Malignant Gastric Neoplasm | CURATED_BROADER | 0.80 |
Interventions
Interventions (6)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| 5-Fluorouracil | Drug | Fluorouracil | ALIAS |
| Capecitabine | Drug | Capecitabine | ALIAS |
| Cisplatin | Drug | Cisplatin | ALIAS |
| Pertuzumab | Drug | Pertuzumab | ALIAS |
| Placebo | Drug | — | UNRESOLVED |
| Trastuzumab | Drug | Trastuzumab | ALIAS |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Pertuzumab + Trastuzumab + Chemotherapy
- description
- Participants will receive pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine \[capecitabine or 5-fluorouracil\]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants will continue to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
- interventionNames
- Drug: 5-Fluorouracil
- Drug: Capecitabine
- Drug: Cisplatin
- Drug: Pertuzumab
- Drug: Trastuzumab
- type
- PLACEBO_COMPARATOR
- label
- Placebo + Trastuzumab + Chemotherapy
- description
- Participants will receive placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine \[capecitabine or 5-fluorouracil\]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants will continue to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Histologically confirmed metastatic adenocarcinoma of the stomach or GEJ * Measurable or evaluable non-measurable disease as assessed by the investigator according to RECIST v1.1 criteria * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Life expectancy greater than equal to (\>/=) 3 months Exclusion Criteria: * Previous cytotoxic chemotherapy for advanced (metastatic) disease * Evidence of disease progression documented within 6 months after completion of prior neoadjuvant or adjuvant cytotoxic chemotherapy, or both, or radiotherapy for GEJ adenocarcinoma * Previous treatment with any HER2-directed therapy, at any time, for any duration * Previous exposure to any investigational treatment within 30 days before the first dose of study treatment * Radiotherapy within 30 days before the first dose of study treatment (within 2 weeks if given as palliation to bone metastases, if recovered from all toxicities) * History or evidence of brain metastases * Clinically significant active gastrointestinal (GI) bleeding (Grade \>/=2 according to National Cancer Institute \[NIC\]-Common Terminology Criteria for Adverse Events Version 4.0 \[CTCAEv.4.0\]) * Residual toxicity resulting from previous therapy (for example, hematologic, cardiovascular, or neurologic toxicity that is Grade \>/=2). Alopecia is permitted * Other malignancy (in addition to gastric cancer \[GC\]) within 5 years before enrollment, except for carcinoma in situ of the cervix or squamous or basal cell carcinoma of the skin that has been previously treated with curative intent * Inadequate hematologic, renal or liver function * Pregnant or lactating women * History of congestive heart failure of any New York Heart Association (NYHA) criteria * Angina pectoris requiring treatment * Myocardial infarction within the past 6 months before the first dose of study drug * Clinically significant valvular heart disease or uncontrollable high-risk cardiac arrhythmia * History or evidence of poorly controlled hypertension * Baseline left ventricular ejection fraction (LVEF) value less than (\<) 55 percent (%) * Any significant uncontrolled intercurrent systemic illness * Positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection
References
Publications (4)
- DERIVEDTabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Siddiqui A, Heeson S, Kiermaier A, Macharia H, Restuccia E, Kang YK. Pertuzumab, trastuzumab, and chemotherapy in HER2-positive gastric/gastroesophageal junction cancer: end-of-study analysis of the JACOB phase III randomized clinical trial. Gastric Cancer. 2023 Jan;26(1):123-131. doi: 10.1007/s10120-022-01335-4. Epub 2022 Sep 6. PMID 36066725
- DERIVEDLiu T, Qin Y, Li J, Xu R, Xu J, Yang S, Qin S, Bai Y, Wu C, Mao Y, Wu H, Ge Y, Shen L. Pertuzumab in combination with trastuzumab and chemotherapy for Chinese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer: a subpopulation analysis of the JACOB trial. Cancer Commun (Lond). 2019 Jun 24;39(1):38. doi: 10.1186/s40880-019-0384-6. PMID 31234927
- DERIVEDKirschbrown WP, Wang B, Nijem I, Ohtsu A, Hoff PM, Shah MA, Shen L, Kang YK, Alsina M, Girish S, Garg A. Pharmacokinetic and exposure-response analysis of pertuzumab in patients with HER2-positive metastatic gastric or gastroesophageal junction cancer. Cancer Chemother Pharmacol. 2019 Sep;84(3):539-550. doi: 10.1007/s00280-019-03871-w. Epub 2019 Jun 10. PMID 31183514
- DERIVEDTabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Cheng K, Song C, Wu H, Eng-Wong J, Kim K, Kang YK. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018 Oct;19(10):1372-1384. doi: 10.1016/S1470-2045(18)30481-9. Epub 2018 Sep 11. PMID 30217672