What side effects are associated with this type of intervention?

Common treatments for prostate cancer, including PARP inhibitors like olaparib and rucaparib, often lead to side effects such as anemia, thrombocytopenia, neutropenia, nausea, fatigue, and gastrointestinal issues like diarrhea and constipation. Androgen receptor antagonists such as enzalutamide and apalutamide can cause fatigue, hypertension, falls, and seizures. Chemotherapy agents like docetaxel may result in febrile neutropenia, hair loss, and peripheral neuropathy. These side effects vary in severity and frequency, and patients should discuss them with their healthcare provider to manage and mitigate these effects effectively.

What prior FDA approvals exist?

Several PARP inhibitors have been approved by the FDA for the treatment of prostate cancer, particularly for castration-resistant prostate cancer (CRPC) with specific genetic mutations. Olaparib was approved for patients with metastatic CRPC who have deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene mutations, including BRCA1/2. Rucaparib received accelerated approval for patients with BRCA-mutated metastatic CRPC who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy. These approvals highlight the role of PARP inhibitors in targeting DNA repair mechanisms in prostate cancer treatment.

What other types of research exist?

Promising alternatives to AZD5305 for prostate cancer patients include Olaparib (AZD2281), which has shown efficacy in various cancers with DNA repair deficiencies, and Rucaparib, which has been studied in patients with BRCA mutations. Additionally, Enzalutamide and Abiraterone are androgen receptor signaling inhibitors that have shown benefits in castration-resistant prostate cancer (CRPC). Combining these agents with osteoclast inhibitors like Denosumab may also reduce fracture risks in metastatic cases.

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PARP Inhibitor

AZD5305 for Advanced Cancers (PETRA Trial)

Phase 1 & 2

Recruiting

Led By Timothy Yap

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

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

Must have

Age ≥ 18 at the time of screening

For Part B: Patients must not have received prior therapy with a PARPi-based regimen (either as a treatment or as maintenance)

Must not have

History of persisting (> 2 weeks) severe pancytopenia due to any cause

Treatment with nitrosourea or mitomycin C within 6 weeks of the first dose of study treatment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from screening to confirmed progressive disease (approximately 1 year)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called AZD5305, which blocks a protein that helps cancer cells repair their DNA. It aims to see if the drug is safe and effective for patients with advanced solid tumors. By stopping the repair process, the drug hopes to kill cancer cells. AZD5305 has shown better tolerance in patients compared to earlier similar drugs.

Who is the study for?

Adults over 18 with advanced solid tumors suitable for the study, who have not had certain treatments like strong CYP3A4 inhibitors or inducers, recent major surgery, or live vaccines. They should have a life expectancy of at least 12 weeks and an ECOG performance status of 0-2.

What is being tested?

The trial is testing AZD5305 alone or combined with other anti-cancer drugs to see if it's safe and effective against various advanced cancers. It involves patients who may/may not have had previous PARPi-based therapy depending on the part of the study they're in.

What are the potential side effects?

Possible side effects include nausea, vomiting, fatigue, allergic reactions to components in the drug mixtures, potential blood disorders such as pancytopenia (low count of all types of blood cells), and risks associated with organ function impairment.

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 never been treated with PARPi-based therapy.

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My cancer is getting worse.

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I can take care of myself and am up and about more than half of the day.

Exclusion Criteria

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

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I have had severe low blood counts for more than 2 weeks.

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I haven't taken nitrosourea or mitomycin C in the last 6 weeks.

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I have a condition that increases my risk of bleeding.

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I have had serious heart or stroke issues in the last 6 months.

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I have been diagnosed with myelodysplastic syndrome or acute myeloid leukemia.

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I cannot take pills due to severe nausea, vomiting, or past major gut surgery.

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I am not taking any strong or moderate drugs or supplements that affect liver enzymes.

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I haven't had cancer treatment in the last 3 weeks.

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I am on more than 10 mg of prednisone or its equivalent daily.

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I am not taking medication that affects heart rhythm.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from screening to confirmed progressive disease (approximately 1 year)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from screening to confirmed progressive disease (approximately 1 year)

This trial's timeline: 3 weeks for screening, Varies for treatment, and from screening to confirmed progressive disease (approximately 1 year) for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

The number of subjects with adverse events/serious adverse events

The number of subjects with dose-limiting toxicity (DLT), as defined in the protocol.

Secondary study objectives

Best percentage change in target lesion

CA125 response (ovarian cancer)

Duration of Response

+30 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

6Treatment groups

Experimental Treatment

Group I: Module 6 AZD5305 + CamizestrantExperimental Treatment2 Interventions

AZD5305 + Camizestrant

Group II: Module 5 AZD5305 + Datopotamab DeruxtecanExperimental Treatment2 Interventions

AZD5305 + Dato-DXd

Group III: Module 4: AZD5305 + Trastuzumab DeruxtecanExperimental Treatment2 Interventions

AZD5305 + T- DXd

Group IV: Module 3: AZD5305 + Carboplatin with or without PaclitaxelExperimental Treatment3 Interventions

AZD5305 + Carboplatin with or without Paclitaxel

Group V: Module 2: AZD5305 + PaclitaxelExperimental Treatment2 Interventions

AZD5305 + Paclitaxel

Group VI: Module 1: AZD5305 MonotherapyExperimental Treatment1 Intervention

AZD5305 Monotherapy

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Camizestrant

2023

Completed Phase 1

~40

AZD5305

2022

Completed Phase 1

~20

Paclitaxel

2011

Completed Phase 4

~5450

Carboplatin

2014

Completed Phase 3

~6120

0 / 14Eligibility 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

Prostate cancer treatments often target specific molecular pathways to inhibit cancer growth and progression. PARP inhibitors, like the experimental AZD5305, block the enzyme poly(ADP-ribose) polymerase (PARP), which is crucial for DNA repair. By inhibiting PARP, these drugs exploit the defective DNA repair mechanisms in cancer cells, particularly those with BRCA mutations, leading to cell death. Androgen receptor inhibitors, such as enzalutamide and apalutamide, prevent androgens from binding to their receptors, thereby inhibiting the growth-promoting effects of these hormones on prostate cancer cells. Chemotherapy agents like docetaxel disrupt cell division, leading to cancer cell death. These treatments are vital as they offer targeted approaches to manage and potentially improve outcomes for prostate cancer patients, especially those with advanced or resistant forms of the disease.