A phase 1 trial to assess the safety, tolerability and anti-tumor activity of increasing doses of the drugs AZD6738 and gemcitabine in combination.

Phase 1

Active, not recruiting

• Conditions: Locally advanced or metastatic solid tumour.; MedDRA version: 20.1 Level: LLT Classification code 10065143 Term: Malignant solid tumour System Organ Class: 100000004864; MedDRA version: 20.0 Level: LLT Classification code 10049280 Term: Solid tumour System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-003935-12-GB
• Lead Sponsor: Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-03-13
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 55

Inclusion Criteria

To be included in the trial the participant must meet all of the following criteria:

• Written informed consent to participate.
• Aged 18 years and over.
• ECOG performance status of 0 or 1.
• Dose escalation phase only: Patients with inoperable/unresectable, histologically proven, locally advanced or metastatic solid tumour that has progressed on standard therapy, or patients unwilling to receive standard therapy.
• Treatment expansion phase only: Patients with inoperable, histologically proven, locally advanced or metastatic pancreatic adenocarcinoma that has progressed on conventional chemotherapy, or patients unwilling to receive standard therapy.
• Documented evidence of progression (radiological or clinical) prior to trial entry.
• Estimated life expectancy of =12 weeks.
• Measurable tumour lesions that can be accurately assessed at baseline by computed tomography (CT) and are suitable for repeated assessment as per RECIST 1.1 and considered accessible for core biopsy.
• Women of childbearing potential, male participants and their partners are required, and must be willing, to use 2 highly effective forms of contraception for the duration of the trial and for six (6) months after the completion of the trial treatment. Women of non-childbearing potential must meet one of the following:
• Documented postmenopausal (defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments).
• Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy with last menses >1 year ago (excluding tubal ligation, radiation-induced oophorectomy).
• Documented amenorrhoeic for 12 months (defined as women under the age of 50 years with serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and plasma oestradiol levels in the postmenopausal range for the institution).
• Patient is willing and able to comply with the protocol for the duration of the trial.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25

Exclusion Criteria

• Diagnosis of ataxia-telangiectasia syndrome.
• Women who are pregnant or breast-feeding.
• Women of child-bearing potential and male participants who are unwilling to use 2 highly effective forms of contraception during the trial and for 6 months after the completion of the trial treatment.
• Cytotoxic chemotherapy within 21 days of start of treatment (greater than five half-lives is allowed for washout in patients treated with non-cytotoxic drugs). Exposure to a small molecule IMP within 30 days or 5 half-lives (whichever is longer) prior to the start of treatment.
• Palliative radiotherapy within 21 days of start of treatment.
• Immunotherapy within 42 days of start of treatment.
• New treatment with bisphosphonates or denosumab for bone metastases within 5 days of start of treatment (patients can receive a stable dose of bisphosphonates or denosumab for bone metastases before and during the trial as long as these were started at least 5 days prior to start of treatment).
• Major surgery within 2 weeks of start of treatment (patients must have recovered from any effects of major surgery).
• Current treatment with steroids (doses of >10mg of prednisone or equivalent) or other immunosuppressive drugs within 14 days of start of treatment.
• Any other malignancy which has been active or treated within the past three years (with the exception of cervical intra-epithelial neoplasia, non-melanoma skin cancer, ductal carcinoma in situ, stage 1 grade 1 endometrial carcinoma, or other solid tumours curatively treated with no evidence of disease for =5 years prior).
• Current treatments with known potent cytochrome P (CYP) 3A inhibitors, potent CYP3A inducers, CYP3A4 and/or CYP2B6 substrates with a narrow therapeutic index or Pgp modulators (wash out period of five half-lives, but three weeks for St. John’s Wort, see Appendix 5). The use of herbal supplements or ‘folk remedies’ is not permitted.
• Impaired hepatic or renal function defined as:
o AST or ALT >2.5 x ULN (or 5 times if liver metastasis).
o Total bilirubin >1.5 x ULN.
o Glomerular filtration rate (GFR) (calculated by Cockcroft-Gault) of <41 ml/min.
• Inadequate bone marrow reserve or organ function defined as:
o Absolute neutrophil count <1.5 x 10*9/L.
o Platelet count <100 x 10*9/L with no blood transfusions in the past 28 days.
o Haemoglobin <90 g/L with no platelet transfusions in the past 28 days.
• INR =1.25 above the normal range.
• Haematuria +++.
• Known history of cardiac dysfunction within the last 6 months defined as:
o Myocardial infarction
o NYHA Class II/III/IV heart failure
o Unstable angina pectoris
o Unstable cardiac arrhythmias not controlled with a pacemaker or medication (e.g. complete left bundle branch block or third degree heart block).
• Any of the following cardiac criteria:
o Mean resting corrected QT interval (QTc) >470 msec for women, and >450 msec for men obtained from 3 electrocardiograms (ECGs) 2-5 minutes apart using the Fredericia formula.
o Patients with relative hypotension (<90/60 mm Hg) or

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified