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RecruitingLast updated: 26 February 2024

IGNITE: This phase II trial is testing an oral targeted therapy (adavosertib) in patients with high grade serous ovarian cancerA Phase II signal-seeking trial of Adavosertib (AZD1775) targeting recurrent high grade serous ovarian cancer (HGSC) with Cyclin E1 (CCNE1) over-expression with and without gene amplification to determine the clinical benefit rate

Clinical summary

Summary

Eligible patients will receive 300mg of oral adavosertib on Days 1-5 and then Days 8-12 of each 21-day cycle, for a maximum duration of 24 months. Patients eligible to join this trial should be aged 18 and above and have platinum resistant high grade serous ovarian cancer with Cyclin E1 over-expression.

Conditions

This trial is treating patients with high grade serous ovarian cancer

Cancer

Female Reproductive System Cancers Gynaecological

Age

People18+

Phase

II

Trial Acronym

IGNITE

More information

Trial Identifiers

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Trial sponsor

Australia New Zealand Gynaecological Oncology Group (ANZGOG)

Scientific Title

A Phase II signal-seeking trial of Adavosertib (AZD1775) targeting recurrent high grade serous ovarian cancer (HGSC) with Cyclin E1 (CCNE1) over-expression with and without gene amplification to determine the clinical benefit rate

Eligibility

Inclusion

1. Patient has provided written informed consent for the Main part of the study
2. Patient continues to meet all pre-screening inclusion criteria
3. Patient’s tumour has a confirmed Cyclin E over-expression defined by IHC
- Tumours with Cyclin E over-expression will have CCNE1 copy number assessed by FISH to determine which cohort patients will be assigned
4. Patient has platinum resistant HGSC, defined as progressive disease by imaging < 6 months from last date of most recent platinum-based therapy, or symptomatic, rising CA-125 based on GCIG criteria
a. Patients who are refractory (progress during or within 4 weeks) to 2nd or subsequent lines of platinum-based chemotherapy are eligible.
b. Patients who are primary platinum refractory (progress during or within 4 weeks of 1st line chemotherapy) are considered ineligible
5. Patient has recurrent disease which is measurable by RECIST 1.1 and/or evaluable disease by GCIG CA-125 criteria
- The number of patients with only GCIG CA-125 evaluable disease is capped at 10 in each cohort
6. Patient has adequate bone marrow, liver and renal function with baseline laboratory values within 7 days prior to registration:
- Absolute neutrophil count (ANC) =1.5 x 109/L
- Haemoglobin (HgB) = 90 g/L for mono-therapy
- Platelets =100 x 109/L
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =3 x upper limit of normal (ULN) or =5 x ULN if known hepatic metastases.
- Serum bilirubin within normal limits (WNL) or =1.5 x ULN in patients with liver metastases; or total bilirubin =3.0 x ULN with direct bilirubin WNL in patients with documented Gilbert’s Syndrome.
- Serum creatinine =1.5 x ULN, or measured creatinine clearance (CrCl) =45 mL/min as calculated by the Cockcroft-Gault method (confirmation of creatinine clearance is only required when creatinine is >1.5 x institutional ULN)
7. Females of childbearing potential must practice highly effective methods of birth control for the duration of the study and for at least 6 months after last study drug.
8. Patient has consented to the use of their collected archival FFPE specimen and peripheral blood samples as detailed in the protocol for translational research, including but not limited to DNA, RNA and protein-based biomarker detection.

Exclusion

1. Patient has had prior treatment with Wee1 kinase inhibition
2. Use of anti-cancer treatment drug less than or equal to 21 days or 5 half-lives (whichever is shorter) prior to registration; for drugs for which 5 half-lives is less than or equal to 21 days, a minimum of 10 days between termination of the prior treatment and registration into the study is required
- Patients on luteinizing hormone-releasing hormone (LHRH) analogue treatment for more than 6 months are allowed entry into the study and may continue at the discretion of the investigator.
3. Patient has had previous radiation therapy completed less than or equal to 7 days prior to registration
4. Patient has had major surgical procedures less than or equal to 28 days prior to registration, or minor surgical procedures less than or equal to 7 days prior to registration:
- No waiting period required following port-a-cath or other central venous access placement
5. Patient has persistent Grade > 1 toxicity from prior therapy (except alopecia or anorexia)
6. Patient has an inability to swallow oral medications; Note: Patients may not have a percutaneous endoscopic gastrostomy (PEG) tube or be receiving total parenteral nutrition (TPN)
- Patients with symptoms subacute or acute bowel obstruction in three months prior to Cycle 1 Day 1 of main study are excluded
7. Patient has known malignant central nervous system (CNS) disease other than neurologically stable, treated brain metastases, defined as metastasis having no evidence of progression or hemorrhage for at least 2 weeks after treatment:
- Patients must be off any systemic corticosteroids for the treatment of brain metastases for at least 14 days prior to registration
8. Patient has had prescription or non-prescription drugs or other products known to be moderate to strong inhibitors/inducers of CYP3A4. If the drug could be discontinued, then a wash out of greater than or equal to 2 weeks prior to Day 1 of dosing is required and the drug will be withheld throughout the study until 2 weeks after the last dose of study drug.
- Co-administration of aprepitant or fosaprepitant during this study is prohibited
- The use of sensitive CYP3A4 substrates could be used with caution. Clinical data showed that adavosertib is a weak inhibitor of CYP3A4.
9. Patient has taken the following herbal preparations within 7 days prior to registration:
- St. John's wort, kava, ephedra (ma hung), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto and ginseng.
10. Patient has known hypersensitivity or contraindication to the components of the study drug adavosertib
11. Patient has any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) greater than or equal to class 2:
- Unstable angina pectoris
- Congestive heart failure
- Acute myocardial infarction
- Conduction abnormality not controlled with pacemaker or medication
- Significant ventricular or supraventricular arrhythmias (patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible)
- Mean resting corrected QTc interval using the Fridericia formula (QTcF) > 470 msec (as calculated per institutional standards) obtained from 3 electrocardiograms (ECGs) 2-5 minutes apart at study entry, or congenital long QT syndrome
- History of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected
12. Pregnant or breastfeeding women
13. Patient has serious active infection at the time of registration, or another serious underlying medical condition that would impair the ability of the patient to receive study treatment
14. Patient has a presence of other active invasive cancers that do not harbor CCNE1 amplification
15. Patient has a known positive test result for human immunodeficiency virus (HIV) or active hepatitis B or C virus infection

Inclusion

  • You are able to swallow medication by mouth.
  • You have had treatment, but your cancer has come back.

Exclusion

  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria.

Ask your doctor if this trial could be right for you.

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