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AKT Inhibitor/MEK Inhibitor/ATR Inhibitor

Combination Therapy for Triple Negative Breast Cancer

Phase 2

Recruiting

Led By Zahi Mitri, MD, MS

Research Sponsored by OHSU Knight Cancer Institute

Eligibility Criteria Checklist

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

Must have

Metastatic TNBC with specific hormone receptor and HER2 status

Participants with or without germline BRCA mutated TNBC

Must not have

Participants unable to swallow orally administered medication and participants with gastrointestinal disorders likely to interfere with absorption of the study medication

Concomitant use of specified medications

Timeline

Screening 3 weeks

Treatment Varies

Follow Up death (any cause) up to 1 year post treatment

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing 3 different combinations of drugs or 1 drug by itself to see if it can effectively treat patients with a certain type of breast cancer.

Who is the study for?

This trial is for adults with metastatic triple negative breast cancer who haven't been treated with PARP inhibitors like olaparib. They must be able to consent, have a life expectancy of at least 16 weeks, and agree to biopsies and contraception if applicable. Exclusions include certain medication use, other cancers unless cured over 5 years ago, CNS metastases, major surgery recently, or conditions affecting drug absorption.

What is being tested?

The study tests the effectiveness of olaparib combined with durvalumab (a monoclonal antibody), selumetinib (MEK inhibitor), capivasertib (AKT inhibitor) or ceralasertib alone (ATR inhibitor) in treating metastatic triple negative breast cancer. The goal is to see if these combinations can stop tumor growth by blocking enzymes needed for cell growth.

What are the potential side effects?

Potential side effects may include nausea, fatigue, blood count changes from olaparib; immune-related reactions from durvalumab; skin rash or heart issues from selumetinib; hyperglycemia or rash from capivasertib; and anemia or fatigue from ceralasertib. Each patient's experience may vary.

Eligibility Criteria

Inclusion Criteria

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

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My breast cancer has spread, is triple-negative, and lacks certain hormone receptors and HER2.

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My triple-negative breast cancer may or may not have a BRCA mutation.

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I am 18 years old or older.

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I agree to have a tumor biopsy after 2 weeks of starting olaparib treatment.

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I have never been treated with PARP inhibitors like olaparib.

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I have a tumor that can be measured and biopsied.

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I have received treatments for breast cancer that has spread.

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I am fully active and can carry on all pre-disease activities without restriction.

Exclusion Criteria

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

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I cannot swallow pills or have a stomach condition that affects medication absorption.

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I am currently taking certain medications.

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My tumor shows high levels of androgen receptor.

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I have been diagnosed with MDS/AML or show signs of these conditions.

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I have active brain metastases or carcinomatous meningitis.

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I am currently taking hormone therapy for a condition that is not cancer.

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I am not currently receiving any cancer treatments.

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I am currently on antibiotics for an infection.

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I have had a bone marrow or double cord blood transplant.

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I have active hepatitis B or C.

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My condition is critical due to organ failure.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ death (any cause) up to 1 year post treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~death (any cause) up to 1 year post treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and death (any cause) up to 1 year post treatment 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)

Secondary study objectives

Clinical benefit rate (CBR)

Duration of response (DOR)

Incidence of grade 3+ acute toxicity

+2 more

Other study objectives

Change in QOL as measured by EORTC QLQBR23

Change in quality of life (QOL) as measured by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)

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

Dizziness

Hyperglycaemia

Aspartate aminotransferase increased

Thrombocytopenia

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

4Treatment groups

Experimental Treatment

Group I: Arm IV (ceralasertib)Experimental Treatment3 Interventions

Patients receive ceralasertib PO BID on days 1-14 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles.

Group II: Arm III (olaparib, capivasertib)Experimental Treatment4 Interventions

Patients receive olaparib PO BID on days 1-28 of each cycle and capivasertib PO BID 4 days on and 3 days off of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles.

Group III: Arm II (olaparib, selumetinib)Experimental Treatment4 Interventions

Patients receive olaparib PO BID on days 1-28 of each cycle and selumetinib PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles.

Group IV: Arm I (olaparib, durvalumab)Experimental Treatment4 Interventions

Patients receive olaparib PO BID on days 1-28 of each cycle and durvalumab intravenously (IV) over 1 hour on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Capivasertib

2021

Completed Phase 1

~130

Olaparib

2007

Completed Phase 4

~2190