Olaparib and Ramucirumab in Treating Patients With Metastatic or Locally Recurrent Gastric or Gastroesophageal Junction Cancer That Cannot Be Removed by Surgery

Completed · Phase 1/Phase 2

Conditions studied: Metastatic Esophageal Carcinoma, Metastatic Gastric Carcinoma, Metastatic Gastroesophageal Junction Adenocarcinoma, Recurrent Esophageal Carcinoma, Recurrent Gastric Carcinoma, Recurrent Gastroesophageal Junction Adenocarcinoma, Stage III Esophageal Cancer AJCC v7, Stage III Gastric Cancer AJCC v7, Stage IV Esophageal Cancer AJCC v7, Stage IV Gastric Cancer AJCC v7, Unresectable Esophageal Carcinoma, Unresectable Gastric Carcinoma, Unresectable Gastroesophageal Junction Adenocarcinoma

In brief

This phase I/II trial studies the side effects and best dose of olaparib when given together with ramucirumab and how well they work in treating patients with gastric or gastroesophageal junction cancer that has spread to other places in the body (metastatic), has come back (recurrent), or cannot be removed by surgery (unresectable). Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as ramucirumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving olaparib and ramucirumab may work better in treating patients with gastric or gastroesophageal junction cancer compared to ramucirumab and paclitaxel (a chemotherapy drug) or ramucirumab alone.

Key facts

Study ID

NCT03008278

Run by

National Cancer Institute (NCI)

People needed

51

Starts

2018-02-06

Expected to finish

2025-08-13

Last updated by the study team

2026-02-03

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• The patient must have histologically confirmed, gastric carcinoma, including gastroesophageal junction (GEJ) adenocarcinoma (patients with adenocarcinoma of the distal esophagus are eligible if the primary tumor involves the GEJ)
• The patient has metastatic disease or locally recurrent, unresectable disease
• The patient must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
• The patient must have experienced disease progression during or within 4 months after the last dose of chemotherapy for metastatic disease, during or within 6 months after the last dose of adjuvant chemotherapy, or have been intolerant of previous chemotherapy
• The patient must have experienced disease progression or intolerance as outlined above after treatment with 1 or more prior chemotherapies
• All previous treatments are acceptable as long as they did not contain bevacizumab, ramucirumab or PARP inhibitors
• Elevation in tumor markers without radiographic evidence of disease progression is not satisfactory for progression on previous treatment
• The patient is >= 18 years of age
• The patient has a life expectancy of >= 16 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1 (Karnofsky >= 60%)
• Hemoglobin >= 10 g/dL with no blood transfusions (packed red blood cells and platelet transfusions) in the past 28 days (within 28 days prior to administration of study treatment)
• White blood cells (WBC) > 3 x 10\^9/L (within 28 days prior to administration of study treatment)
• Absolute neutrophil count (ANC) >= 1.5 10\^9/L (within 28 days prior to administration of study treatment)
• Platelet count >= 100 X 10\^9/L (within 28 days prior to administration of study treatment)
• No features suggestive of myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) on peripheral blood smear or bone marrow biopsy, if clinically indicated (within 28 days prior to administration of study treatment)
• Total bilirubin =< 1.5 x the institutional upper limit of normal (ULN) (within 28 days prior to administration of study treatment)
• Aspartate aminotransferases (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN unless liver metastases are present in which case they must be =< 5 x ULN (within 28 days prior to administration of study treatment)
• Calculated serum creatinine clearance >= 60 mL/min/1.73 m\^2 (within 28 days prior to administration of study treatment)
• Proteinuria with urinary protein =< 1+ on dipstick or routine urinalysis, or a 24-hour urine collection for protein < 1000 mg of protein in 24 hours (within 28 days prior to administration of study treatment)
• Coagulation parameters (international normalized ratio [INR], activated partial thromboplastin time [aPTT]) =< 1.25 x institutional limits, except where a lupus anti-coagulant has been confirmed or the patient is on warfarin; patients on full dose anticoagulation must be on a stable dose for at least 14 days; if receiving warfarin, the patient must have an INR =< 3.0 without any evidence of active bleeding within 14 days prior to first dose of study treatment or a pathologic condition that carries a high risk of bleeding (tumor involvement with major blood vessels or varices) (within 28 days prior to administration of study treatment)
• Postmenopausal or evidence of non-childbearing status for women of childbearing potential a negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1; postmenopausal is defined as:
• Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
• Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the postmenopausal range for women under 50
• Radiation-induced oophorectomy with last menses > 1 year ago
• Chemotherapy-induced menopause with > 1 year interval since last menses

You may not qualify if…

• Patients with untreated brain metastases are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; a scan to confirm the absence of brain metastases is not required; the patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment; patients with spinal cord compression are also excluded unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Common Terminology Criteria for Adverse Events [CTCAE] grade 1 or baseline, with the exception of alopecia)
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
• The patient has experienced any grade 3-4 gastrointestinal bleeding within 3 months prior to randomization
• The patient has experienced any arterial thrombotic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to enrollment
• The patient has an ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, uncontrolled thrombotic or hemorrhagic disorder, or any other serious uncontrolled medical disorder in the opinion of the investigator
• The patient has an ongoing or active psychiatric illness or social situation that would limit compliance with study requirements
• Clinically significant peripheral vascular disease or vascular disease (abdominal aortic aneurysm > 5 cm) or aortic dissection; if known history of abdominal aortic aneurysm with >= 4 cm in diameter, all of the following must be met
• An ultrasound within the last 6 months required to document that it is =< 5 cm
• Patient must be asymptomatic from the aneurysm
• Blood pressure must be well controlled as defined in this protocol
• The patient has uncontrolled or poorly controlled hypertension despite standard medical management as defined in this protocol
• NYHA classification of III or IV
• A resting electrocardiogram (EKG) with a corrected QT (QTC) >= 470 msec detected on 2 or more time points within a 2 hour period or family history of long QT syndrome; if the EKG demonstrates QTC >= 470 msec, the patient will only be eligible if a repeat EKG demonstrates QTC =< 470 msec
• History of hypertensive crisis or hypertensive encephalopathy within 3 years
• Major surgery within 28 days of starting study treatment and patients must have recovered from any effects of any major surgery
• An open biopsy, non-healing wound, ulcer or significant traumatic injury within 28 days prior to starting treatment (percutaneous, endobronchial, and endoscopic biopsies are allowed)
• The patient has received chemotherapy, radiotherapy (except for palliative reasons), immunotherapy, or targeted therapy for gastric cancer within 3 weeks of study treatment
• The patient has received any investigational therapy within 4 weeks of enrollment
• The patient has received prior therapy with bevacizumab, ramucirumab or any PARP inhibitor, including olaparib
• Patients must not have evidence of coagulopathy or bleeding diathesis; therapeutic anticoagulation for prior thromboembolic events is permitted; the clinical indication for therapeutic anticoagulation must be clearly documented prior to enrollment and must be discussed with the principal investigator (PI); due to risk of serious bleeding with ramucirumab, patients on greater than or equal to 2 anti-thrombotic agents, including but not limited to anti-platelet agents (nonsteroidal anti-inflammatory drugs [NSAIDS]/aspirin, clopidogrel), heparin, low molecular weight heparin, warfarin and a direct thrombin inhibitor will be excluded
• The patient has elective or planned major surgery to be performed during the course of the clinical trial
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib and ramucirumab
• Patients with a known hypersensitivity to olaparib or any of the excipients of the product
• Patients with a known hypersensitivity to the combination/comparator agent

Where it is running

• City of Hope Corona — Corona, California, United States
• City of Hope Comprehensive Cancer Center — Duarte, California, United States
• City of Hope Antelope Valley — Lancaster, California, United States
• University of California Davis Comprehensive Cancer Center — Sacramento, California, United States
• UCSF Medical Center-Mount Zion — San Francisco, California, United States
• City of Hope South Pasadena — South Pasadena, California, United States
• City of Hope Upland — Upland, California, United States
• Smilow Cancer Hospital-Derby Care Center — Derby, Connecticut, United States
• Smilow Cancer Hospital Care Center-Fairfield — Fairfield, Connecticut, United States
• Smilow Cancer Hospital Care Center - Guilford — Guilford, Connecticut, United States
• Smilow Cancer Hospital Care Center at Saint Francis — Hartford, Connecticut, United States
• Smilow Cancer Center/Yale-New Haven Hospital — New Haven, Connecticut, United States
• Yale University — New Haven, Connecticut, United States
• Yale-New Haven Hospital North Haven Medical Center — North Haven, Connecticut, United States
• Smilow Cancer Hospital-Orange Care Center — Orange, Connecticut, United States
• Smilow Cancer Hospital-Torrington Care Center — Torrington, Connecticut, United States
• Smilow Cancer Hospital Care Center-Trumbull — Trumbull, Connecticut, United States
• Smilow Cancer Hospital-Waterbury Care Center — Waterbury, Connecticut, United States
• Smilow Cancer Hospital Care Center - Waterford — Waterford, Connecticut, United States
• University of Florida Health Science Center - Gainesville — Gainesville, Florida, United States
• Brigham and Women's Hospital — Boston, Massachusetts, United States
• Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• Wayne State University/Karmanos Cancer Institute — Detroit, Michigan, United States
• Weisberg Cancer Treatment Center — Farmington Hills, Michigan, United States

Full record on ClinicalTrials.gov

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