What side effects are associated with this type of intervention?

Common treatments for solid malignancies, such as chemotherapy, targeted therapy, and immunotherapy, have a range of side effects. Chemotherapy agents like carboplatin often cause hematologic toxicities such as neutropenia, anemia, and thrombocytopenia, as well as nausea, vomiting, and fatigue. Targeted therapies, such as Olaparib, can lead to anemia, nausea, fatigue, and increased risk of infections. Immunotherapy agents like durvalumab may cause immune-related adverse events, including colitis, pneumonitis, hepatitis, and endocrinopathies. These side effects require careful monitoring and management to ensure patient safety.

What prior FDA approvals exist?

Several FDA-approved treatments for solid malignancies involve DNA damage response inhibitors and immune checkpoint inhibitors, similar to the combinations being studied with Ceralasertib. Olaparib, a PARP inhibitor, is approved for BRCA-mutated ovarian and breast cancers. Immune checkpoint inhibitors like pembrolizumab and nivolumab, which target PD-1, are approved for various cancers including melanoma, non-small cell lung cancer, and renal cell carcinoma. These treatments highlight the therapeutic strategy of combining DNA repair inhibition with immune modulation.

What other types of research exist?

Promising alternatives to Ceralasertib for solid malignancies include: 1) Ceritinib in combination with gemcitabine and cisplatin, particularly for tumors with ALK or ROS1 fusions. 2) ARRY-382 in combination with pembrolizumab, which has shown preliminary efficacy in advanced solid tumors. 3) Olaparib, especially in combination with other agents like abiraterone for prostate cancer or as a monotherapy for ovarian cancer.

← Back to Search

Other

Ceralasertib Combinations for Cancer

Phase 1 & 2

Recruiting

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

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

Must have

Patients in Module 2 Part B2 Study expansion must have advanced gastric adenocarcinoma (including GEJ) with ATM proficient tumours

Patients in Module 2 Part B4 Study expansion must have Second or third line triple negative breast cancer (TNBC)

Must not have

Patients in Module 4 with type I or type II diabetes

Patients in Module 5 with known hypersensitivity to PARP including AZD5305

Timeline

Screening 3 weeks

Treatment Varies

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

Awards & highlights

No Placebo-Only Group

Summary

This study is evaluating whether a drug may help treat cancer.

Who is the study for?

This trial is for adults with advanced cancers, including specific types of lung, breast, ovarian cancer and other solid tumors. Eligibility varies by module: some require certain genetic mutations or prior treatments. Exclusions include previous ATR inhibitor exposure, contraindications to study drugs like olaparib and durvalumab, diabetes (in Module 4), and bad reactions to ceralasertib.

What is being tested?

The trial tests ascending doses of ceralasertib alone or in combination with chemotherapy agents like carboplatin or novel anti-cancer agents such as olaparib and durvalumab. It aims to find the optimal dose combinations while monitoring safety closely. Effects on food absorption and ECG parameters are also studied.

What are the potential side effects?

Potential side effects may include typical reactions from chemotherapy such as nausea, fatigue, blood count changes; immune-related issues from durvalumab; allergic reactions; plus any unique effects related to ceralasertib which could involve gastrointestinal symptoms or impact on liver function.

Eligibility Criteria

Inclusion Criteria

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

Select...

My advanced stomach cancer is ATM proficient.

Select...

My breast cancer is triple negative and I am seeking second or third line treatment.

Select...

My advanced stomach cancer lacks the ATM protein.

Select...

I am 18 years old or older.

Select...

My solid tumor cannot be treated with standard methods anymore.

Exclusion Criteria

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

Select...

I have type I or type II diabetes.

Select...

I am allergic to PARP inhibitors, including AZD5305.

Select...

I have been treated with an ATR inhibitor before.

Select...

I cannot take olaparib due to health reasons.

Select...

My heart's electrical activity (QTc) is over 470 msec or I have a family history of long QT syndrome.

Select...

I have been diagnosed with ataxia telangiectasia.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

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

Screening ~ 3 weeks

Treatment ~ Varies

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

This trial's timeline: 3 weeks for screening, Varies for treatment, and from first dose 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

Module 4 only: Effect of ceralasertib on ECG parameters (HR, PR, QRS and QTcF) by ECG recordings

Module 4 only: Effect of food on ceralasertib absorption by Intensive PK assessments after a single oral dose of ceralasertib (Part A)

The number of subjects with adverse events/serious adverse events

Secondary study objectives

Area under the plasma concentration-time curve (AUC) for Carboplatin

Area under the plasma concentration-time curve (AUC) for Olaparib

Area under the plasma concentration-time curve (AUC) for ceralasertib

+26 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

14Treatment groups

Experimental Treatment

Group I: Module 5 Part BExperimental Treatment1 Intervention

Module 5 Part B: cohort expansions of ceralasertib in combination with AZD5305 in ovarian patients at dose, frequency and schedule from Module 5 Part A.

Group II: Module 5 Part AExperimental Treatment1 Intervention

Module 5 Part A: ascending doses of ceralasertib will be administered in combination with AZD5305 to patients to define the MTD, RP2D. In case this first dose level is not tolerated, alternative schedules will be evaluated.

Group III: Module 4 (FE/QT)Experimental Treatment3 Interventions

Ceralasertib monotherapy will be administered on a number of days during Cycle 0 to assess the effect of food on ceralasertib absorption and effect of ceralasertib on ECG parameters under various conditions (fasted, fed, steady state). From C1 onwards, patients who participated in C0 will be allocated to either ceralasertib in combination with olaparib or durvalumab, or ceralasertib monotherapy and assessed for safety.

Group IV: Module 3 Part BExperimental Treatment1 Intervention

Module 3 Part B: cohort expansions of ceralasertib in combination with durvalumab in HNSCC or NSCLC patients at dose, frequency and schedule from Module 3 Part A.

Group V: Module 3 Part AExperimental Treatment1 Intervention

Module 3 Part A: cohort escalation of ceralasertib in combination with durvalumab in HNSCC or NSCLC patients to define the dose, frequency and schedule of ceralasertib and durvalumab to take into Module 3 Part B. Additionally, Module 3 Part A will include a serial tumour biopsy cohort to evaluate the Proof of Mechanism of ceralasertib in HNSCC and NSCLC patients.

Group VI: Module 2 Part B5Experimental Treatment1 Intervention

Patients with BRCA mutant or RAD51C/D mutant (either germline or somatic) or HRD-positive status epithelial ovarian, fallopian tube, or primary peritoneal cancer according to local testing. Patients must be platinum sensitive and previously progressed on a licensed PARPi. The cohort will be split into 2 groups: Cohort 1 - without intervening chemotherapy following progression on a PARPi, Cohort 2 - with intervening chemotherapy following progression on a PARPi. Patients will receive ceralasertib and olaparib, at the RP2D dose, frequency and schedule established from Module 2 Part A2.

Group VII: Module 2 Part B4Experimental Treatment1 Intervention

Module Part B4: Patients with second or third line triple negative breast cancer with no known BRCA mutations. This expansion will be enriched for patients with disease harbouring a HRR-related gene mutation (HRRm) will receive ceralasertib with olaparib, at dose, frequency and schedule recommended from Module 2 Part A2.

Group VIII: Module 2 Part B3Experimental Treatment1 Intervention

Module 2 Part B3: Patient with second or third line breast cancer with BRCA mutations (somatic or germline), excluding HER2 positive breast cancer will receive ceralasertib with olaparib, at dose, frequency and schedule recommended from Module 2 Part A2.

Group IX: Module 2 Part B2Experimental Treatment1 Intervention

Module 2 part B2: Patients with second line 'ATM proficient' gastric adenocarcinoma including GEJ adenocarcinoma will receive ceralasertib with olaparib, at dose, frequency and schedule recommended from Module 2 Part A2.

Group X: Module 2 Part B1Experimental Treatment1 Intervention

Module 2 Part B1: Patients with second line 'ATM deficient' gastric adenocarcinoma including GEJ adenocarcinoma will receive ceralasertib with olaparib, at dose, frequency and schedule recommended from Module 2 Part A2.

Group XI: Module 2 Part A2Experimental Treatment1 Intervention

Module 2 Part A2: ascending doses of ceralasertib will be administered in combination with olaparib to patients to define the dose, frequency and schedule of ceralasertib and olaparib to take into Module 2 Part B.

Group XII: Module 2 Part A1Experimental Treatment1 Intervention

Module 2 Part A1: ascending doses of ceralasertib will be administered alone to define the maximum tolerated dose (MTD) and/or a continuous, tolerable Recommended Dose (RD) to take into Module 2 Part A2.

Group XIII: Module 1 Part BExperimental Treatment1 Intervention

Module 1 Part B: patients with advanced lung adenocarcinoma with low expression of ATM will receive ceralasertib and carboplatin, at the dose, frequency and schedule recommended from Module 1 Part A.

Group XIV: Module 1 Part AExperimental Treatment1 Intervention

Module 1 Part A: ascending doses of ceralasertib in combination with carboplatin AUC5 will be administered to patients to define the maximum tolerated dose (MTD) and/or a continuous, tolerable Recommended Dose (RD).

0 / 11Eligibility 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

Common treatments for solid malignancies include kinase inhibitors, chemotherapy, and immunotherapy. Kinase inhibitors, such as Ceralasertib, target specific enzymes (kinases) involved in cancer cell growth and survival, thereby inhibiting tumor progression. Chemotherapy uses cytotoxic drugs to kill rapidly dividing cancer cells, though it can also affect normal cells, leading to side effects. Immunotherapy, including agents like pembrolizumab, enhances the body's immune response against cancer cells. These treatments are crucial for solid malignancies as they offer targeted approaches to disrupt cancer cell proliferation and survival, potentially leading to better outcomes and fewer side effects compared to traditional therapies.

Pan-phosphatidylinositol 3-kinase inhibition with buparlisib in patients with relapsed or refractory non-Hodgkin lymphoma.Androgen receptor (AR) aberrations in castration-resistant prostate cancer.