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Protocol No. NCI10066

Principal Investigator Uboha, Nataliya

Phase I/II

Age Group Adult

Scope National

Sponsor Type Externally Peer-Reviewed

Title A Phase 1 / 2 Study of Olaparib in Combination with Ramucirumab in Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma

Objective
Phase 1:
  • The purpose of this portion of the study is to test the safety of the combination of olaparib and ramucirumab at different doses of olaparib to find out what side effects, if any, it has on patients. There will be about 9 patients taking part in the phase 1 portion of the study. This will be conducted before phase 2 begins, which is described below.
    Phase 2:
  • The purpose of this study is to test any good and bad effects of the combination of olaparib and ramucirumab. The combination of olaparib and ramucirumab could shrink your cancer, but it could also cause side effects. Researchers hope to learn if the study drug will shrink the cancer compared to its present size. Ramucirumab has already been FDA-approved to treat gastric cancer, and olaparib has been approved for the treatment of other cancers. Ramucirumab decreases the oxygen delivery to tumor cells, which inhibits tumor growth and has also been shown to decrease the ability of tumors to repair DNA effectively. Olaparib also inhibits the ability for tumors to repair DNA and is most effective in tumors that already have impaired DNA repair. It is hoped that combining olaparib with ramucirumab will improve getting rid of tumors better than just the ramucirumab used alone. There will be 40 patients taking part in the phase 2 portion of the study. You will only be enrolled in one phase of the study, phase 1 or 2. Your study doctor will tell you in which study phase you will be enrolled.

  • Treatment
    Phase 1(Part 1) olaparib and ramucirumab.
    Phase 2 (Part 2):
  • In phase 2, all participants will receive the same treatment. Patients will receive ramucirumab in combination with the ideal dose of olaparib that was determined in phase 1

  • Description A Phase 1 / 2 Study of Olaparib in Combination with Ramucirumab in Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma

    Key Eligibility
  • Histologically confirmed, gastric carcinoma, including GEJ adenocarcinoma (patients with adenocarcinoma of the distal esophagus are eligible if the primary tumor involves the GEJ)
  • Metastatic disease or locally recurrent, unresectable disease, measurable disease by RECIST v1.1
  • Must have experienced disease progression during or within 4 months afterthe 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
  • All previous treatments are acceptable as long as they did not contain bevacizumab, ramucirumab or PARP inhibitors
  • At least 18 years of age or older
  • ECOG PS 0-1, Karnofsky greater than or equal to 60%
  • Normal organ and marrow function as defined by the protocol
  • Can not be pregnant or breastfeeding
  • Male and Female of childbearing potential must agree to adequate birth control as defined by the protocol
  • Must be willing to undergo a biopsy prior to treatment, an on treatment biopsy at week 16 is optional if felt to be safe in the opinion of the investigator
  • Must be able to tolerate oral medications by mouth, and not have agastrointestinal illness that would preclude absorption of olaparib
  • Adequate controlled blood pressure as defined by the protocol
  • Patients who have the following risk factors are considered to be at increased risk for cardiac toxicity and must have documented LVEF by Echocardiogram greater than institution’s lower limit of normal
    EXCLUSION
  • Untreated brain metastases are excluded
  • Patient has experienced any grade 3-4 gastrointestinal bleeding within 3 months prior to randomization
  • Arterial thrombotic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to enrollment
  • 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
  • Clinically significant peripheral vascular disease or vascular disease
  • NYHA classification of III or IV
  • A resting EKG with a QTC greater than or equal to 470 msec
  • History of hypertensive crisis or hypertensive encephalopathy within 3 years
  • Received prior therapy with bevacizumab, ramucirumab or any PARP inhibitor, including olaparib
  • Evidence of coagulopathy or bleeding diathesis
  • Immunocompromised patients, this includes HIV-positive patients
  • known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as detectable HCV RNA) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority
  • Features suggestive of myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) on peripheral blood smear or bone marrow biopsy, if clinically indicated
  • Prior allogeneic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
  • Current signs and/or symptoms of bowel obstruction within 1 month prior to starting study drugs
  • History of abdominal fistula, intra-abdominal abscess, or gastrointestinal perforation within the last 3 months
  • History of hemoptysis within the last 1 month
  • Current use of natural herb products or other complementary alternative medications. If used previously, patients must have at least 1-week washout and must stop using them while participating in this study

  • Applicable Disease Sites Esophagus; Stomach

    Status Open

    Participating Institutions UW Hospital and Clinics