An open-label phase Ib time-to-event continual reassessment method of dose-escalation of tolinapant (ASTX660) in combination with standard radical chemotherapy and radiotherapy in patients with cervical cancer
- Conditions
- Adenocarcinoma or squamous cell carcinoma of the cervixCancer
- Registration Number
- ISRCTN18574865
- Lead Sponsor
- niversity of Southampton
- Brief Summary
2024 Protocol article in https://pubmed.ncbi.nlm.nih.gov/38849715/ (added 11/06/2024)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- Female
- Target Recruitment
- 42
1. Histologically confirmed adenocarcinoma or squamous cell carcinoma of the cervix stage IB2/IIB/IIIB
2. Suitable for radical treatment with radiotherapy and cisplatin (using a standard dose of 45Gy in 25 daily fractions over 5 weeks with weekly cisplatin 40 mg/m2)
3. Adequate haematological parameters:
3.1. Haemoglobin = 90 g/l
3.2. Neutrophil count = 1.5 x 109/l
3.3. Platelets = 100 x 109/l
4. Adequate biochemical parameters:
4.1. Bilirubin = 1.5 x ULN
4.2. AST and ALT =2.0 x ULN
4.3. ALP = 2.5 x ULN
5. Lipase and Amylase =1.2 x ULN
6. GFR Calculated (by Cockcroft-Gault formula or other accepted formula) or measured directly as = 50 mL/min
7. Aged 16 years and over
8. ECOG Performance Status of 0-1
9. Willing and able to give written informed consent
1. Previous pelvic radiotherapy
2. Liver cirrhosis, or chronic liver disease Child-Pugh Class B or C
3. Pregnancy or breastfeeding (Women of child bearing potential (WOCBP) must have a negative serum pregnancy test at screening)
4. Patients of child-bearing potential who are not able to use a highly effective method of contraception
5. Any investigational medicinal product (IMP) within 30 days prior to consent
6. Major surgery within 30 days prior to enrolment
7. Hypersensitivity to tolinapant, excipients of the drug product, or other components of the study treatment regimen
8. Patients with known HIV infection
9. Patients with known active hepatitis B virus (HBV; chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test) or hepatitis C. Patients with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody and the absence of HBsAg) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA
10. Coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, unstable arrhythmias, unstable angina, left bundle branch block, third-degree heart block, pacemakers or congestive cardiac failure (New York Heart Association = grade 2) within 6 months prior to enrolment
11. Any patient who has received a live vaccine within 4 weeks of initiation of their treatment (COVID-19 vaccination is allowed)
12. Conditions requiring systemic treatment with either corticosteroid (= 20 mg daily prednisolone or equivalent) or other immunosuppressive medications within 14 days of study drug administration.
13. Prior anticancer treatments or therapies within the indicated time window prior to the first dose of study treatment (tolinapant), as follows:
13.1.Cytotoxic chemotherapy or radiotherapy within 3 weeks prior and any encountered treatment-related toxicities (excepting alopecia) not resolved to Grade 1 or less.
13.2. Skin-directed treatments, including topicals and radiation within 2 weeks prior
13.3. Monoclonal antibodies within 4 weeks prior and any encountered treatment-related toxicities not resolved to Grade 1 or less
13.4. Small molecules or biologics (investigational or approved) within the longer of 2 weeks or 5 half-lives prior to study treatment and any encountered treatment-related toxicities not resolved to Grade 1 or less
13.5. At least 6 weeks must have elapsed since CAR-T infusion and subjects must have experienced disease progression, and not have residual circulating CAR-T cells in peripheral blood (based on a local assessment). Any encountered treatment-related toxicities must have resolved to Grade =1.
14. Patients taking a QT-prolonging agent
15. Use of a concomitant medication which is a strong CYP3A4 inhibitor
16. Abnormal left ventricular ejection fraction (LVEF) of <50% on echocardiogram (ECHO)
17. History of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy
18. Screening 12-lead electrocardiogram (ECG) with measurable QTc interval of =470 msec (according to either Fridericia’s or Bazett’s correction)
19. Any other active malignancy
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method