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

NCT03008278 | Completed Phase 1 Results FDA Drug

• 4 other identifiers: NCI-2016-02049200002140710066UM1CA186689
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 32

Brief Summary

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.

Conditions

Stage IV Esophageal Cancer AJCC v7; 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 Gastric Cancer AJCC v7; Unresectable Esophageal Carcinoma; Unresectable Gastric Carcinoma; Unresectable Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicity and Maximum Tolerated Dose of Olaparib (Phase I)

  Will be assessed by National Cancer Institute (NCI) Common Terminology Criteria (CTCAE) for Adverse Events version 5.0. The safety profile and adverse event reporting were collected in an intent to treat analysis so data from all patients were included in the overall analysis and there was never any plan nor intent to evaluate or report the safety profile separately. These are not two different arms of the same study, the phase 1 part of this was a lead in to the phase 2.

  Up to 28 days

• Objective Response Rate (Phase II)

  Will be defined as complete or partial response assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Presented are the count of those that were considered to have responded while in treatment.

  Up to 2 years

Secondary Outcomes (5)

• Progression Free Survival

  From start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years

• Overall Survival

  Up to 2 years

• BROCA-HR Status: Progression Free Survival

  Up to 6 months

• BROCA-HR Status: Overall Survival

  Up to 2 years

• Count of Participants With Adverse Events

  Up to 2 years

Other Outcomes (2)

• BROCA HR Assay

  Up to 6 years

• Tumor Cells for PDX Model, and Biobanked Tumor Tissue and Peripheral Blood

  Up to 6 years

Study Arms (1)

Treatment (olaparib, ramucirumab)

EXPERIMENTAL

Patients receive olaparib PO BID on days 1-14 of each cycle and ramucirumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Drug: Olaparib; Biological: Ramucirumab

Interventions

Olaparib DRUG

Give PO

Also known as: AZD 2281, AZD-2281, AZD2281, KU 0059436, KU-0059436, KU0059436, Lynparza, Olanib, Olaparix, PARP Inhibitor AZD2281

Treatment (olaparib, ramucirumab)

Ramucirumab BIOLOGICAL

Given IV

Also known as: Anti-VEGFR-2 Fully Human Monoclonal Antibody IMC-1121B, Cyramza, IMC 1121B, IMC-1121B, IMC1121B, LY 3009806, LY-3009806, LY3009806, Monoclonal Antibody HGS-ETR2

Treatment (olaparib, ramucirumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (32)

City of Hope Corona

Corona, California, 92882, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

City of Hope Antelope Valley

Lancaster, California, 93534, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

UCSF Medical Center-Mount Zion

San Francisco, California, 94115, United States

Location

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

City of Hope Upland

Upland, California, 91786, United States

Location

Smilow Cancer Hospital-Derby Care Center

Derby, Connecticut, 06418, United States

Location

Smilow Cancer Hospital Care Center-Fairfield

Fairfield, Connecticut, 06824, United States

Location

Smilow Cancer Hospital Care Center - Guilford

Guilford, Connecticut, 06437, United States

Location

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, 06105, United States

Location

Smilow Cancer Center/Yale-New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Yale-New Haven Hospital North Haven Medical Center

North Haven, Connecticut, 06473, United States

Location

Smilow Cancer Hospital-Orange Care Center

Orange, Connecticut, 06477, United States

Location

Smilow Cancer Hospital-Torrington Care Center

Torrington, Connecticut, 06790, United States

Location

Smilow Cancer Hospital Care Center-Trumbull

Trumbull, Connecticut, 06611, United States

Location

Smilow Cancer Hospital-Waterbury Care Center

Waterbury, Connecticut, 06708, United States

Location

Smilow Cancer Hospital Care Center - Waterford

Waterford, Connecticut, 06385, United States

Location

University of Florida Health Science Center - Gainesville

Gainesville, Florida, 32610, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Weisberg Cancer Treatment Center

Farmington Hills, Michigan, 48334, United States

Location

Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

New Brunswick, New Jersey, 08903, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt Breast Center at One Hundred Oaks

Nashville, Tennessee, 37204, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Esophageal Neoplasms; Stomach Neoplasms

Interventions

olaparib; Ramucirumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Michael Cecchini, MD
• Organization: Yale School of Medicine

michael.cecchini@yale.edu

(203) 200-4422

Study Officials

• Michael Cecchini

  Yale University Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2016
• First Posted: January 2, 2017
• Study Start: February 6, 2018
• Primary Completion: June 30, 2023
• Study Completion: August 13, 2025
• Last Updated: February 3, 2026
• Results First Posted: June 4, 2025

Record last verified: 2026-01

Locations

US (32)