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PARP Inhibitor

Olaparib + Sapacitabine for Breast Cancer

Phase 1

Waitlist Available

Led By Filipa Lynce, MD

Research Sponsored by Dana-Farber Cancer Institute

Eligibility Criteria Checklist

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

Must have

Participants enrolling to the phase I portion of the study must have evaluable or measurable disease

Patients with HER2-positive disease must have received and progressed on two lines of HER2-directed therapy in the metastatic setting

Must not have

For enrollment during phase II: patients who have received more than 3 prior lines of cytotoxic chemotherapy for metastatic disease

Uncontrolled intercurrent illness

Timeline

Screening 3 weeks

Treatment Varies

Follow Up assessed from the time of the first patient registration to the time that the last patient comes off protocol therapy, up to 41 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is attempting to find a more effective treatment for breast cancer, specifically for those with a BRCA mutation. The study will be testing a combination of two drugs, sapacitabine and olaparib, to see if they are more effective than either drug used alone.

Who is the study for?

This trial is for adults with metastatic or unresectable breast cancer that has a BRCA mutation. Candidates must have progressed after certain therapies, depending on their cancer type. They should be able to take oral medication and agree to use effective contraception. People with recent treatments, active hepatitis or HIV, heart issues, prior PARP inhibitor treatment, MDS/AML history, major surgery complications within 2 weeks before the study start are excluded.

What is being tested?

The study tests a combination of two drugs: Sapacitabine (CYC682) and Olaparib (Lynparza™), as potential treatments for breast cancer with BRCA mutations. It's structured in phases; phase I evaluates safety while phase II measures how well the disease responds according to RECIST criteria.

What are the potential side effects?

Potential side effects include risks during pregnancy hence contraception requirements; organ inflammation; digestive disturbances due to oral intake of medication; blood disorders from bone marrow impact; fatigue from overall drug effects on body function.

Eligibility Criteria

Inclusion Criteria

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

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My cancer can be measured or seen on tests.

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My HER2-positive cancer has worsened after two different HER2 treatments.

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My breast cancer is confirmed and cannot be removed by surgery.

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I can swallow and keep down pills.

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I agree to use two effective birth control methods during the study and for 6 months after.

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My cancer is hormone receptor-positive and has worsened despite hormone therapy.

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I am 18 years old or older.

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I am a woman who is either postmenopausal or not currently pregnant.

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I am fully active or can carry out light work.

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I am willing and able to follow the study's treatment and visit schedule.

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I have a harmful BRCA1 or BRCA2 gene mutation.

Exclusion Criteria

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

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I have had more than 3 chemotherapy treatments for my cancer after it spread.

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I do not have any uncontrolled illnesses.

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I am not taking strong or moderate CYP3A inhibitors.

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I have never been treated with sapacitabine.

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

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I am allergic to medications similar to sapacitabine or olaparib.

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I have a history of or signs pointing to blood disorders like MDS or AML.

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I or someone in my family has long QT syndrome.

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I currently have inflammation in my lungs.

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

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I have active Hepatitis B, C, or am HIV positive.

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I have never been treated with a PARP inhibitor like olaparib.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ assessed from the time of the first patient registration to the time that the last patient comes off protocol therapy, up to 41 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~assessed from the time of the first patient registration to the time that the last patient comes off protocol therapy, up to 41 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and assessed from the time of the first patient registration to the time that the last patient comes off protocol therapy, up to 41 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Maximum Tolerated Dose (MTD)

Objective Response Rate

Recommended Phase II dose (RPIID)

Secondary study objectives

Dose Limiting Toxicity

Progression-Free Survival

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

4Treatment groups

Experimental Treatment

Group I: Dose Level 3: Sapacitabine (250 mg) + Olaparib (300 mg)Experimental Treatment2 Interventions

* Olaparib will be administered orally twice daily for each 28-day cycle * Sapacitabine will be administered orally once daily on days 1 - 5 and 8 - 12 of every 28-day cycle

Group II: Dose Level 2: Sapacitabine (200 mg) + Olaparib (300 mg)Experimental Treatment2 Interventions

* Olaparib will be administered orally twice daily for each 28-day cycle * Sapacitabine will be administered orally once daily on days 1 - 5 and 8 - 12 of every 28-day cycle

Group III: Dose Level 1: Sapacitabine (150 mg) + Olaparib (300 mg)Experimental Treatment2 Interventions

* Olaparib will be administered orally twice daily for each 28-day cycle * Sapacitabine will be administered orally once daily on days 1 - 5 and 8 - 12 of every 28-day cycle

Group IV: Dose Level -1: Sapacitabine (100 mg) + Olaparib (300 mg)Experimental Treatment2 Interventions

* Olaparib will be administered orally twice daily for each 28-day cycle * Sapacitabine will be administered orally once daily on days 1 - 5 and 8 - 12 of every 28-day cycle

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Olaparib

2007

Completed Phase 4

~2190

Sapacitabine

2011

Completed Phase 3

~490