AZD5305 for Advanced Cancers

(PETRA Trial)

Recruiting at 66 trial locations

Overseen By AstraZeneca Breast Cancer Study Locator Service

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: AstraZeneca

Must not be taking: CYP3A4 inhibitors, QT drugs

Disqualifiers: Cardiac conditions, Brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

702 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether the experimental treatment AZD5305, used alone or with other cancer drugs, is safe and effective against advanced solid tumors, which form in tissues like organs or muscles. Researchers are testing various combinations of AZD5305 with different agents to identify the most effective approach. Individuals with advanced cancers that are worsening despite treatment might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, providing participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires stopping certain medications, such as those that strongly affect liver enzymes (CYP3A4 inhibitors or inducers) and drugs that affect heart rhythms. You should discuss your current medications with the trial team to see if any need to be stopped.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that AZD5305, a type of cancer drug known as a PARP inhibitor, is promising in terms of safety. Studies have found that AZD5305 is generally well-tolerated when used alone, with few patients needing to pause their treatment.

When combined with other drugs like camizestrant or paclitaxel, AZD5305 still appears safe. Patients have shown good tolerance to these combinations, and the combination with camizestrant has demonstrated encouraging safety results.

AZD5305 is also being tested with other cancer drugs such as carboplatin, trastuzumab deruxtecan, and datopotamab deruxtecan. These combinations are part of ongoing studies to ensure their safety for patients. While detailed information on side effects for these specific combinations isn't always available, the studies aim to confirm their safety.

Overall, early-phase trials have studied AZD5305 and its combinations, focusing on safety. These trials are designed to observe how the body reacts to the treatment and ensure its safety for further research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AZD5305 because it represents a new frontier in cancer treatment. Unlike traditional therapies that often target cancer cells broadly, AZD5305 is a PARP inhibitor, specifically designed to target DNA repair processes in cancer cells, potentially leading to more effective treatment with fewer side effects. What sets AZD5305 apart is its combination with other drugs like Camizestrant, Paclitaxel, Carboplatin, and novel agents like Trastuzumab Deruxtecan and Datopotamab Deruxtecan, which could enhance its effectiveness against various advanced cancers. This innovative approach aims to exploit specific weaknesses in cancer cells, offering hope for more personalized and precise cancer therapy.

What evidence suggests that this trial's treatments could be effective for advanced cancers?

Studies have shown that the drug AZD5305, which blocks a protein called PARP1, effectively targets cancers with BRCA1/2 mutations. This drug prevents cancer cells from repairing themselves, aiding in their destruction. In this trial, participants may receive AZD5305 with chemotherapy drugs like carboplatin, which has demonstrated even better results, indicating stronger cancer-fighting effects. Other participants may receive AZD5305 with drugs like camizestrant or datopotamab deruxtecan, which have shown increased ability to kill cancer cells in lab studies. Overall, early research results are promising for AZD5305 in treating advanced solid tumors. ^{1 5 6 7 8}

Who Is on the Research Team?

Timothy Yap

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

My organs and bone marrow are working well.

My advanced cancer is confirmed and deemed suitable for this study.

My cancer is confirmed and considered suitable for this study's treatment.

Exclusion Criteria

My heart condition meets the study's requirements.

I haven't taken any experimental drugs recently.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AZD5305 as monotherapy or in combination with anti-cancer agents

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

40 days

Long-term follow-up

Participants are monitored for progression-free survival and other long-term outcomes

1 year

What Are the Treatments Tested in This Trial?

Interventions

• AZD5305
• Carboplatin
• Dato-DXd
• Paclitaxel
• T-Dxd

Trial Overview 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.

How Is the Trial Designed?

Group I: Module 6 AZD5305 + Camizestrant Experimental Treatment 2 Interventions

AZD5305 + Camizestrant

Group II: Module 5 AZD5305 + Datopotamab Deruxtecan Experimental Treatment 2 Interventions

AZD5305 + Dato-DXd

Group III: Module 4: AZD5305 + Trastuzumab Deruxtecan Experimental Treatment 2 Interventions

AZD5305 + T- DXd

Group IV: Module 3: AZD5305 + Carboplatin with or without Paclitaxel Experimental Treatment 3 Interventions

AZD5305 + Carboplatin with or without Paclitaxel

Group V: Module 2: AZD5305 + Paclitaxel Experimental Treatment 2 Interventions

AZD5305 + Paclitaxel

Group VI: Module 1: AZD5305 Monotherapy Experimental Treatment 1 Intervention

AZD5305 Monotherapy

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

AZD4635, a potential anticancer therapy, showed comparable oral bioavailability between its nanosuspension and capsule forms, but a high-fat meal significantly reduced the rate of absorption, delaying peak concentration by over 2 hours without affecting the overall extent of absorption.

Co-administration with fluvoxamine resulted in a substantial increase in AZD4635 exposure, particularly in smokers, indicating that drug interactions can significantly enhance its pharmacokinetics, while all treatment regimens were well tolerated with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive clinical pharmacology characterization of AZD4635 in healthy participants to support dosing considerations. Moorthy, G., Pouliot, GP., Graham, L., et al.[2023]

AZD1775, a Wee1 inhibitor, demonstrated good penetration into brain tumors in patients with recurrent glioblastoma, achieving a median unbound tumor-to-plasma concentration ratio of 3.2, which suggests effective delivery of the drug to the tumor site.

The study provided evidence of clinical biological activity in glioblastoma, as indicated by the suppression of the Wee1 pathway and increased DNA damage, with no reported drug-related adverse events, highlighting its potential as a safe treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 0 Trial of AZD1775 in First-Recurrence Glioblastoma Patients. Sanai, N., Li, J., Boerner, J., et al.[2020]

AZD5305, a new PARP1 inhibitor, is better tolerated than older PARP inhibitors in patients with specific cancer types and genetic mutations, including ovarian, HER2-negative breast, pancreatic, and prostate cancers.

In a phase I/IIa trial involving 40 patients, 25% showed a partial response to treatment, indicating promising efficacy for this next-generation drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AZD5305 More Tolerable than Earlier PARP Agents. [2022]

AZD5363, an oral medication for advanced solid tumors, showed a more tolerable safety profile with intermittent dosing compared to continuous dosing, leading to a recommended dose of 480 mg twice daily on a 4 days on, 3 days off schedule.

Preliminary results indicated antitumor activity, particularly in patients with the Akt1 (E17K) mutation, suggesting that this mutation may help predict which patients are more likely to respond to AZD5363 treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of AZD5363 in Japanese patients with advanced solid tumors. Tamura, K., Hashimoto, J., Tanabe, Y., et al.[2019]

A phase II study of the PARP inhibitor olaparib confirmed its clinical benefits for cancer patients with inherited BRCA1 and BRCA2 mutations, particularly in advanced breast and ovarian cancers.

The study also provided evidence that olaparib is effective against pancreatic and prostate cancers, expanding its potential use in treating various cancer types associated with these genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib shows promise in multiple tumor types. [2014]

In a phase I study involving 21 patients with advanced solid tumors, the combination of olaparib and topotecan was found to have a maximum tolerated dose (MTD) of topotecan 1.0 mg/m²/day for 3 days plus olaparib 100 mg twice daily, primarily due to dose-limiting toxicities like neutropenia and thrombocytopenia.

The study highlighted that while the combination treatment was associated with common adverse events such as fatigue and gastrointestinal issues, the significant hematological side effects led to the decision not to pursue further development of this treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib (AZD2281) in combination with topotecan for the treatment of patients with advanced solid tumors: a phase I study. Samol, J., Ranson, M., Scott, E., et al.[2022]

In the phase 3 JAVELIN Renal 101 trial involving 886 treatment-naive patients with advanced renal cell carcinoma, the combination of avelumab and axitinib significantly improved progression-free survival (PFS) compared to sunitinib, with a median PFS of 13.8 months versus 7.0 months for the PD-L1+ population.

While overall survival (OS) data were still immature, the results suggest that avelumab plus axitinib may offer a promising treatment option for patients with advanced renal cell carcinoma, particularly those with PD-L1+ tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated efficacy results from the JAVELIN Renal 101 trial: first-line avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma. Choueiri, TK., Motzer, RJ., Rini, BI., et al.[2022]

The combination of erlotinib (an EGFR inhibitor) and olaparib (a PARP inhibitor) significantly enhances antitumor effects in ovarian cancer models compared to either drug alone, indicating a promising new treatment strategy.

The study found that this combination therapy works by reducing key signaling pathways (ERK1/2 and AKT) and enhancing autophagy, which may help overcome resistance to conventional therapies in advanced ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of erlotinib and a PARP inhibitor inhibits growth of A2780 tumor xenografts due to increased autophagy. Sui, H., Shi, C., Yan, Z., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06380751

NCT06380751 | Saruparib (AZD5305) Plus Camizestrant ... The primary objective of the study is to measure efficacy of saruparib (AZD5305) plus camizestrant compared with physician's choice CDK4/6i plus ET in patients ...

2. aacrjournals.org aacrjournals.org/clincancerres/article/31/12_Supplement/P2-10-17/754044/Abstract-P2-10-17-A-randomized-phase-III-study-of

A randomized phase III study of first-line saruparib (AZD5305 ... The phase III EvoPAR-Breast01 study (NCT06380751) is evaluating the efficacy and safety of saruparib plus camizestrant, a next-generation oral selective ...

3. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D9722C00001

Saruparib (AZD5305) plus Camizestrant compared with ... The primary objective of the study is to measure efficacy of saruparib (AZD5305) plus camizestrant compared with physician's choice CDK4/6i plus ET in ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04644068

NCT04644068 | Study of AZD5305 as Monotherapy and in ... This research is designed to determine if experimental treatment with PARP inhibitor, AZD5305, alone, or in combination with anti-cancer agents is safe, ...

5. breastcancerstudylocator.com breastcancerstudylocator.com/trial/listing/479895

EvoPAR-BR01: Saruparib (AZD5305) Plus Camizestrant ... The purpose of the EvoPAR-BR01 clinical trial is to compare the safety and efficacy of the investigational combination of saruparib and camizestrant to standard ...

6. breastcancerstudylocator.com breastcancerstudylocator.com/trial/listing/260668

AZD5305 Clinical Trial for Advanced Breast Cancer: PETRA This research is designed to determine if experimental treatment with PARP inhibitor (AZD5305) alone or in combination with anti-cancer agents is safe, ...

7. clinicaltrials.eu clinicaltrials.eu/inn/azd5305/

AZD5305 (Saruparib): A Promising New Cancer Treatment The main goals of the AZD5305 clinical trials are to assess its safety and tolerability, determine optimal dosing, evaluate its pharmacokinetics and ...

8. cancerresearchuk.org cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-of-azd5305-for-certain-types-of-solid-cancers-that-are-getting-worse-petra

A trial of AZD5305 for certain types of solid cancers that are ... Researchers think AZD5305 might help people with certain types of advanced cancer. AZD5305 is a type of targeted cancer drug called a PARP inhibitor. PARP is a ...