What side effects are associated with this type of intervention?

Common treatments for stomach cancer, such as Olaparib (a PARP inhibitor) and Pembrolizumab (a PD-1 inhibitor), have distinct side effect profiles. Olaparib is associated with fatigue, anemia, nausea, and vomiting. Pembrolizumab, on the other hand, can cause immune-related adverse effects, including pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. Both treatments are generally well-tolerated but require careful monitoring for these potential side effects.

What prior FDA approvals exist?

Pembrolizumab, a PD-1 inhibitor, has been studied and shown benefits in the treatment of advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma, particularly in patients with high PD-L1 expression. It has demonstrated improved overall survival and progression-free survival in clinical trials. Olaparib, a PARP inhibitor, is being investigated in combination with pembrolizumab for metastatic gastric and GEJ cancers, although specific FDA approvals for this combination in stomach cancer are not detailed in the provided context. Other related treatments include ramucirumab, which has shown benefits in combination with paclitaxel for previously treated advanced gastric or GEJ adenocarcinoma.

What other types of research exist?

Promising alternatives to Olaparib and Pembrolizumab for stomach cancer patients include Ramucirumab (VEGFR-2 inhibitor), Nivolumab (PD-1 inhibitor), Atezolizumab (PD-L1 inhibitor), and Cemiplimab (PD-1 inhibitor). These therapies have shown potential in clinical trials for advanced gastric cancer.

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PARP Inhibitor

SBRT + Olaparib and Pembrolizumab + Olaparib for Gastric Cancer

Phase 2

Recruiting

Led By Sunnie S Kim, MD

Research Sponsored by University of Colorado, Denver

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participant must be ≥ 18 years of age

Participant must have at least one radiographically-confirmed index lesion that will not undergo RT and is measurable based on RECIST v1.1

Must not have

Has active autoimmune disease that has required systemic treatment in the past 2 years

Has a known history of Human Immunodeficiency Virus (HIV)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 4 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a treatment for patients with advanced stomach and GEJ cancers who have not responded to previous treatments. It uses a drug called olaparib, precise radiation therapy, and a combination of olaparib and pembrolizumab to damage cancer cells' DNA, target them accurately, and help the immune system fight the cancer.

Who is the study for?

Adults with metastatic gastric or gastroesophageal cancer who've had prior treatment including fluoropyrimidine and platinum drugs. They must be able to swallow pills, have good organ function, and a specific gene mutation related to DNA repair. Pregnant women can't join; men and women must agree to contraception.

What is being tested?

This phase II trial tests if olaparib combined with radiation therapy followed by olaparib plus pembrolizumab improves outcomes in patients with certain genetic mutations after previous treatments for their advanced stomach cancers.

What are the potential side effects?

Possible side effects include fatigue, nausea, skin reactions from radiation, immune-related conditions due to pembrolizumab (like inflammation of organs), blood count changes, and potential allergic reactions to the medications used.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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I have at least one tumor that can be measured and hasn't been treated with radiation.

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I have a mutation in a gene linked to DNA repair.

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My stomach cancer is confirmed and can be biopsied.

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I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have an autoimmune disease treated with medication in the last 2 years.

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I have been diagnosed with HIV.

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I have another cancer that is getting worse or was treated in the last 3 years.

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I have had pneumonitis treated with steroids or have it now.

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I have an immune system disorder or have been on high-dose steroids or other immune-weakening medicines recently.

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My stomach and intestines absorb medications normally.

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I have not received a live vaccine in the last 30 days.

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I am currently being treated for an infection.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 4 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~4 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 4 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Objective Response Rate (ORR) of unirradiated tumors

Secondary study objectives

Disease Control Rate (DCR) of Total Cohort and HRD (Homologous Recombination Deficiency) versus HR (Homologous Recombination) proficient.

Duration of Response (DOR) of Total Cohort and HRD (Homologous Recombination Deficiency) versus HR (Homologous Recombination) proficient.

Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0 during concurrent SBRT/olaparib

+2 more

Side effects data

From 2023 Phase 3 trial • 154 Patients • NCT02184195

49%

Nausea

47%

Fatigue

38%

Diarrhoea

29%

Abdominal pain

29%

Anaemia

28%

Constipation

27%

Decreased appetite

27%

Back pain

26%

Vomiting

21%

Arthralgia

19%

Pyrexia

18%

Asthenia

13%

Rash

13%

Nasopharyngitis

11%

Alanine aminotransferase increased

11%

Dyspnoea

10%

Neuropathy peripheral

10%

Cough

10%

Abdominal pain upper

10%

Dyspepsia

10%

Anxiety

10%

Pruritus

Thrombocytopenia

Dizziness

Hyperglycaemia

Aspartate aminotransferase increased

Oedema peripheral

Pain in extremity

Insomnia

Stomatitis

Dry mouth

Headache

Neutropenia

Blood creatinine increased

Weight decreased

Dysgeusia

Blood alkaline phosphatase increased

Neutrophil count decreased

Muscle spasms

Influenza

Influenza like illness

Myalgia

Peripheral sensory neuropathy

Gamma-glutamyltransferase increased

Hypertension

Platelet count decreased

Depression

Lymphopenia

Gastrooesophageal reflux disease

Abdominal distension

Musculoskeletal pain

Flank pain

Cholangitis

Flatulence

Paraesthesia

General physical health deterioration

Bladder papilloma

Pneumonia pneumococcal

Abdominal infection

Bartholinitis

Pneumonia

Cerebrovascular accident

Pneumothorax

Gastric varices haemorrhage

Large intestinal obstruction

Cholecystitis

Anastomotic haemorrhage

Device occlusion

Stent malfunction

Bronchiolitis

Empyema

Syncope

Incisional hernia

Device dislocation

Obstruction gastric

Cardiac failure

Vascular stenosis

Pleural effusion

Incarcerated inguinal hernia

Urinary tract infection

Hypothyroidism

Transient ischaemic attack

Infusion related reaction

Duodenal perforation

Melaena

Bile duct obstruction

Pancreatitis

100%

80%

60%

40%

20%

Study treatment Arm

Olaparib 300 mg Twice Daily (bd)

Placebo

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: HR proficient cohortExperimental Treatment3 Interventions

No identifiable somatic or germline deleterious mutation in DNA Response and Repair pathway

Group II: HR deficient cohortExperimental Treatment3 Interventions

Pre-identified presence of somatic or germline deleterious mutation, as determined by NGS only, in at least one gene critical to DNA repair through homologous recombination, including but not limited to: ARID1A, ATM, ATRX, MRE11A, NBN, PTEN, RAD50/51/51B, BARD1, BLM, BRCA1, BRCA2, BRIP1, FANCA/C/D2/E/F/G/L, PALB2, WRN, CHEK2, CHEK1, BAP1, FAM175A, SLX4, MLL2 or XRCC.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Stereotactic Body Radiation Therapy

2012

Completed Phase 2

~790

Pembrolizumab

2017

Completed Phase 3

~2810

Olaparib

2007

Completed Phase 4

~2190

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

PARP inhibitors, such as Olaparib, work by blocking the PARP enzyme, which helps repair DNA damage in cells. By inhibiting this enzyme, cancer cells with already compromised DNA repair mechanisms (like those with BRCA mutations) accumulate DNA damage and eventually die. Pembrolizumab, a PD-1 inhibitor, works by blocking the PD-1 pathway, which cancer cells exploit to evade the immune system. By inhibiting PD-1, Pembrolizumab reactivates immune cells to recognize and attack cancer cells. These treatments are significant for stomach cancer patients as they offer targeted approaches that can improve outcomes, especially in cases where traditional therapies are ineffective.

Quality of life with first-line pembrolizumab for PD-L1-positive advanced gastric/gastroesophageal junction adenocarcinoma: results from the randomised phase III KEYNOTE-062 study.Platinum-based therapy in adenosquamous pancreatic cancer: experience at two institutions.Promising novel therapies for the treatment of endometrial cancer.