Olaparib + Ramucirumab for Stomach or Esophageal Cancer

No longer recruiting at 34 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4/5 inhibitors, CYP3A4/5 inducers

Disqualifiers: Untreated brain metastases, Active infection, Uncontrolled hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 18

Duration: Ongoing until disease progression or unacceptable toxicity

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, olaparib and ramucirumab, to evaluate their effectiveness in treating stomach or esophageal cancer that cannot be surgically removed, has spread, or has recurred. Olaparib may stop cancer cells from growing by blocking certain enzymes, while ramucirumab might boost the immune system to attack the cancer. The trial compares the effectiveness of these two drugs together against other treatments. People with stomach or gastroesophageal cancer that has worsened despite chemotherapy might be suitable candidates. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering patients a chance to contribute to early-stage cancer treatment advancements.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications, but it does mention that participants cannot take certain medications that strongly affect liver enzymes (CYP3A4/5 inhibitors or inducers) and must have a washout period (time without taking these medications) before starting the trial. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of olaparib and ramucirumab is generally well-tolerated by patients. One study found that this combination works better than ramucirumab alone for treating stomach cancer. These findings suggest that the treatment is safe, with side effects similar to those expected from these types of medicines. However, like any treatment, it may still cause some side effects. Anyone considering participation should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of olaparib and ramucirumab for stomach or esophageal cancer because these treatments target cancer in unique ways. Unlike standard chemotherapy, which attacks rapidly dividing cells, olaparib is a PARP inhibitor that prevents cancer cells from repairing their DNA, leading to cell death. Ramucirumab, on the other hand, is a monoclonal antibody that blocks blood vessel growth in tumors, starving them of nutrients. This dual approach could potentially be more effective in halting cancer progression and improving patient outcomes compared to current therapies.

What evidence suggests that olaparib and ramucirumab might be an effective treatment for stomach or esophageal cancer?

Research has shown that using olaparib with ramucirumab may be promising for treating stomach and esophageal cancers. In this trial, participants will receive the combination of olaparib and ramucirumab. Studies have found that this combination can be more effective than using ramucirumab alone. In clinical trials, patients lived an average of 2.8 months without their cancer worsening, and the average survival time after starting treatment was 7.3 months. These results suggest that this treatment might help patients live longer compared to past outcomes with just ramucirumab. This combination is generally well-tolerated, with most patients not experiencing severe side effects. ^{1 4 6 7 8}

Who Is on the Research Team?

Michael Cecchini

Principal Investigator

Yale University Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with advanced gastric or gastroesophageal junction cancer that has spread and can't be surgically removed. Participants must have a life expectancy of at least 16 weeks, not have used certain drugs like ramucirumab or PARP inhibitors before, and should be able to take oral medications. They cannot join if they've had recent major surgery, uncontrolled medical conditions, known allergies to the study drugs, active infections including hepatitis B/C, other cancers, or are pregnant/breastfeeding.

Inclusion Criteria

Patient has a life expectancy of >= 16 weeks

I have agreed to participate in genetic research.

Willingness 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

Exclusion Criteria

I have had signs or symptoms of a bowel blockage in the last month.

I am allergic to medications similar to olaparib or ramucirumab.

I have had a bone marrow or cord blood transplant in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olaparib orally twice daily and ramucirumab intravenously every 14 days

Ongoing until disease progression or unacceptable toxicity

Every 14 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks initially, then every 6 weeks if no progression, or every 3 months if progression

Initial follow-up at 4 weeks, then every 6 weeks or 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Olaparib
• Ramucirumab

Trial Overview The trial is testing the combination of two drugs: Olaparib and Ramucirumab. Olaparib blocks enzymes needed for tumor cell growth while Ramucirumab helps the immune system attack cancer cells and prevents them from growing/spreading. The goal is to see if this combo works better than current treatments involving just Ramucirumab or chemotherapy.

How Is the Trial Designed?

Group I: Treatment (olaparib, ramucirumab) Experimental Treatment 2 Interventions

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.

Olaparib is already approved in European Union, United States for the following indications:

Approved in European Union as Lynparza for:

• Breast cancer
• Ovarian cancer
• Fallopian tube cancer
• Peritoneal cancer
• Pancreatic cancer
• Prostate cancer
• Endometrial cancer

Approved in United States as Lynparza for:

• Ovarian, fallopian tube, and primary peritoneal cancer
• Breast cancer
• Prostate cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10844282/

NCI10066: a Phase 1/2 study of olaparib in combination with ... Olaparib and ramucirumab is well-tolerated with efficacy that exceeds historical controls with ramucirumab single agent for gastric cancer in a ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38135713/

a Phase 1/2 study of olaparib in combination with ... - PubMed The median progression-free survival (PFS) was 2.8 months (95% CI 2.3-4.2) and median overall survival (OS) was 7.3 months (95% CI 5.7-13.0). Non-statistically ...

3. clinicaltrials.ucbraid.org clinicaltrials.ucbraid.org/trial/NCT03008278

Olaparib and Ramucirumab in Treating Patients With ... Giving olaparib and ramucirumab may work better in treating patients with gastric or gastroesophageal junction cancer compared to ramucirumab and paclitaxel (a ...

4. withpower.com withpower.com/trial/phase-2-adenocarcinoma-10-2017-97188

Olaparib + Ramucirumab for Stomach or Esophageal Cancer Giving olaparib and ramucirumab may work better in treating patients with gastric or gastroesophageal junction cancer compared to ramucirumab and paclitaxel (a ...

5. cancerletter.com cancerletter.com/clinical/20141001_6/

Phase III Cyramza Trial Meets OS Primary Endpoint Treatment with ramucirumab plus paclitaxel significantly reduced the risk of disease progression or death by 37 percent, with a 52 percent increase in median ...

6. trial.medpath.com trial.medpath.com/clinical-trial/3c006fbc69968f15/nct03008278-olaparib-ramucirumab-gastric-cancer

Olaparib and Ramucirumab in Treating Patients ... - MedPath Giving olaparib and ramucirumab may work better in treating patients with gastric or gastroesophageal junction cancer compared to ramucirumab and paclitaxel (a ...

7. link.springer.com link.springer.com/article/10.1007/s10620-025-09021-y

Olaparib Combined with Anti-PD1 Enhances ... PARP inhibitors, effective in BRCA-mutated cancers, show potential in gastric cancer (GC) where homologous recombination defects (e.g., ...

8. jeccr.biomedcentral.com jeccr.biomedcentral.com/articles/10.1186/s13046-021-02005-6

PARP inhibitors in gastric cancer: beacon of hope Combination of olaparib and durvalumab showed promising antitumor activity and safety similar to that previously observed in olaparib and ...