What is the mechanism of action of this treatment?

Berzosertib, an enzyme inhibitor, blocks enzymes essential for tumor cell growth, potentially stopping cancer progression. Irinotecan, a chemotherapy drug, disrupts DNA replication in cancer cells, leading to their death. These mechanisms are significant for Gastroesophageal Junction Adenocarcinoma patients as they offer a targeted approach to hinder cancer cell growth and division, potentially improving treatment outcomes.

What side effects are associated with this type of intervention?

Common side effects of enzyme inhibitors like Berzosertib include fatigue, nausea, and potential hematologic toxicities such as neutropenia and thrombocytopenia. Irinotecan, a chemotherapy agent, often causes diarrhea, nausea, vomiting, and myelosuppression, which can lead to neutropenia and increased risk of infection. Both treatments may also cause general side effects such as hair loss, loss of appetite, and weakness.

What prior FDA approvals exist?

FDA-approved treatments for Gastroesophageal Junction Adenocarcinoma include various chemotherapy agents and targeted therapies. Irinotecan, a chemotherapy drug, has been used in combination with other agents like cisplatin and paclitaxel. Targeted therapies such as trastuzumab, a monoclonal antibody targeting HER2, and ramucirumab, a VEGFR2 antagonist, have also been approved. While berzosertib, an enzyme inhibitor, is still under investigation, other enzyme inhibitors like pembrolizumab, targeting PD-1, have shown efficacy in this cancer type.

What other types of research exist?

Promising novel alternatives for Gastroesophageal Junction Adenocarcinoma include Pembrolizumab, an anti-PD-1 monoclonal antibody approved for patients with high PD-L1 expression, and Nivolumab, another anti-PD-1 monoclonal antibody showing activity in esophageal squamous cell carcinoma. Additionally, Anlotinib, a tyrosine kinase inhibitor, has shown efficacy in esophageal squamous cell carcinoma and may be considered.

PARP Inhibitor

Berzosertib + Irinotecan for Gastric Cancer

Plantation, FL

Phase 2

Waitlist Available

Led By Jordan D Berlin

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

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

Must have

Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) by chest x-ray or as >= 10 mm (>= 1 cm) with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam.

Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 60%).

Must not have

Patients with untreated or symptomatic brain metastases should be 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.

Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1, except alopecia) that was administered more than four weeks prior to starting study therapy.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of berzosertib and irinotecan in patients with advanced gastric or gastroesophageal junction cancer. Berzosertib blocks enzymes needed for cancer growth, and irinotecan kills or stops the spread of cancer cells. Irinotecan has been used in various combinations for treating advanced gastric and gastroesophageal cancers, showing some efficacy but not proving superior to other treatments. The goal is to find a more effective treatment for these difficult-to-treat cancers.

See full description

Who is the study for?

This trial is for adults over 18 with progressive, metastatic, or unresectable gastric or gastroesophageal junction cancer that has a TP53 mutation. Participants must have tried at least two systemic therapies and meet certain health criteria (like blood cell counts). Women of childbearing age and men with partners of childbearing age must use contraception.Check my eligibility

What is being tested?

The trial is testing the effectiveness of combining berzosertib, which blocks enzymes needed for tumor growth, with irinotecan, a chemotherapy drug that kills or stops the spread of cancer cells. The goal is to see if this combination works better than irinotecan alone in treating these cancers.See study design

What are the potential side effects?

Potential side effects may include typical chemotherapy-related issues such as nausea, fatigue, hair loss (alopecia), low blood cell counts leading to increased infection risk or bleeding problems. Berzosertib's side effects are not fully known but could involve similar reactions due to its role in blocking cell growth.

Eligibility Criteria

Inclusion Criteria

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

Select...

I have a tumor that can be measured with imaging or physical exam.

show original

Select...

I am mostly self-sufficient and can carry out daily activities.

show original

Select...

I agree to use effective birth control during and 6 months after the study if I can have children.

show original

Select...

I am 18 years old or older.

show original

Select...

My kidney function is good enough for the trial.

show original

Select...

My cancer is a type that started in the stomach or where the stomach meets the esophagus, and it cannot be removed by surgery.

show original

Exclusion Criteria

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

Select...

I do not have untreated or symptomatic brain metastases.

show original

Select...

I still have side effects from cancer treatment that are not hair loss.

show original

Select...

I do not have any serious illnesses that would stop me from following the study's requirements.

show original

Select...

I have been treated with irinotecan before.

show original

Select...

I have early stage stomach cancer that has not been treated or can be surgically removed.

show original

Select...

I am not pregnant or breastfeeding.

show original

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 1 year for reporting.

Treatment Details

Study Objectives

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

Secondary study objectives

Duration of responses (DOR)

Overall survival (OS)

Time to progression (TTP)

Other study objectives

Presence of other deoxyribonucleic acid (DNA) damage response defects (DDRD)

Side effects data

From 2023 Phase 2 trial • 87 Patients • NCT02567409

78%

Anemia

74%

Platelet count decreased

63%

Nausea

57%

Fatigue

50%

Neutrophil count decreased

46%

Hyponatremia

41%

Creatinine increased

41%

White blood cell decreased

30%

Lymphocyte count decreased

30%

Hypoalbuminemia

28%

Hypomagnesemia

26%

Constipation

26%

Alkaline phosphatase increased

24%

Anorexia

24%

Diarrhea

24%

Vomiting

24%

Edema limbs

24%

Fever

24%

Hypophosphatemia

24%

Dyspnea

22%

Hypokalemia

22%

Hypocalcemia

22%

Hypertension

20%

Aspartate aminotransferase increased

20%

Hyperglycemia

20%

Generalized muscle weakness

20%

Dizziness

17%

Abdominal pain

17%

Pain

17%

Hyperkalemia

17%

Alanine aminotransferase increased

17%

Weight loss

17%

Cough

15%

Urinary tract infection

15%

Dehydration

15%

Back pain

15%

Paresthesia

15%

Hypotension

13%

Sinus tachycardia

13%

Infusion related reaction

13%

Chills

13%

Insomnia

13%

Dysgeusia

13%

Thromboembolic event

11%

Bruising

11%

Bone pain

11%

Myalgia

11%

Peripheral sensory neuropathy

11%

Headache

11%

Hematuria

11%

Nasal congestion

11%

Phlebitis

Anxiety

Syncope

Tinnitus

Hypoproteinemia

LDH increased

Fall

Hiccups

Chronic kidney disease

Epistaxis

Lung infection

Sepsis

Acute kidney injury

Injection site reaction

Skin infection

Hyperphosphatemia

Pain in extremity

Depression

Hydronephrosis

Proteinuria

Sore throat

Rash maculo-papular

Flu like symptoms

Gait disturbance

Weight gain

Hearing impaired

Atrial fibrillation

Leukocytosis

Dry mouth

Increased Blood Urea

Dysphagia

Edema face

Allergic reaction

Blood lactate dehydrogenase increased

Hypoglycemia

Hypoxia

Presyncope

Confusion

Nocturia

Pruritus

Productive cough

Urinary tract pain

Allergic rhinitis

Pulmonary fibrosis

Callus

Neph Tube not draining

Febrile neutropenia

thrombocytosis

Esophagitis

Hyporteinemia

DECREASED ALT

Osteoarthritis

Extrapyramidal disorder

RIGHT WRIST ECCHYMOSIS

Scalp pain

Blood LDH increased

DECREASED AST

Disorientation

Urinary incontinence

Disease progression

Cardiac arrest

Fracture

Hip fracture

Soft tissue infection

Scrotal infection

prostatic abscess

Increased WBC count

Blurred vision

Urinary tract obstruction

Pulmonary edema

Blood LDH Increased

Respiratory failure

Heart Failure

WBC count increased

Supraventricular tachycardia

Ear pain

Left groin mass oozing

Palpitations

Visual acuity decreased

Bloating

Dyspepsia

Gastroesophageal reflux disease

Abdominal distension

Stomach pain

Toothache

Oral pain

Anal hemorrhage

Diverticulosis

IncreasedBlood urea

Non-cardiac chest pain

Localized edema

Tooth infection

Urinary Tract Infection

Herpes zoster

cold sores

Leaking left inguinal area from tumor si

ear infection

Cold symptoms

Rash pustular

Upper respiratory infection

Sinusitis

Malaise

Raised Blood Urea

diaphoresis

Redness around Infusion site

right nipple sensation intermittent

Sepsis of unknown origin

Right Nipple Sensation Intermittent

Skin Tear

Blood bicarbonate decreased

Blood bilirubin increased

Blood Lactate Dehydrogenase Increased

Cardiac troponin I increased

Cardiac troponin T increased

Lactic acid increased

Increased Blood urea

IncreasedPhosphate

Lactate Dehydrogenase Increased

Phosphorus Increased

Hypermagnesemia

Procalcitonin, increased

hyponatremia

Hyperuricemia

hyperphosphatemia

Acidosis

Increased Lactic Dehdrogenase

hypoproteinemia

Hypercalcemia

Hip pain

Arthritis

Dysarthria

Encephalopathy

Scrotal pain

Hemoptysis

Urinary urgency

BILATERAL LOWER LUNG RALES

Wheezing

Gout

Umbiliclal hernia

Altered Mental status

Tremor

Bladder spasm

Renal insufficiency

Hoarseness

Hyperhidrosis

Skin ulceration

petechiae

Rash acneiform

Tinea crusis (groin)

seborrheic dermatitis

tinea cruris (groin)

Mediport Placement

Superficial thrombophlebitis

Petechiae

Hot flashes

100%

80%

60%

40%

20%

Study treatment Arm

Arm A (Berzosertib, Gemcitabine Hydrochloride, Cisplatin)

Arm B (Gemcitabine Hydrochloride, Cisplatin)

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (irinotecan and M6620)Experimental Treatment5 Interventions

Patients receive irinotecan IV over 90 minutes and berzosertib IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo endoscopic or CT assisted biopsy and MRI on study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Magnetic Resonance Imaging

2020

Completed Phase 3

~1180

Irinotecan

2017

Completed Phase 3

~2520

Berzosertib

2021

Completed Phase 2

~170

0 / 12Eligibility 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

Berzosertib, an enzyme inhibitor, blocks enzymes essential for tumor cell growth, potentially stopping cancer progression. Irinotecan, a chemotherapy drug, disrupts DNA replication in cancer cells, leading to their death. These mechanisms are significant for Gastroesophageal Junction Adenocarcinoma patients as they offer a targeted approach to hinder cancer cell growth and division, potentially improving treatment outcomes.