AZD6738 & Gemcitabine as Combination Therapy

NCT03669601 | Unknown Phase 1 DMC

• 1 other identifier: ATRiUM
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

A dose escalation trial to assess the safety of AZD6738 in combination with gemcitabine in participants with advanced solid tumours.

Conditions

Cancer

Keywords

solid tumour; locally advanced; metastatic

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity for the combination of AZD6738 and gemcitabine.

  Number of participants with drug related toxicities reported during Cycle 1 (each cycle is 28 days).

  Through study completion

Secondary Outcomes (1)

• Evaluate anti-tumour effect

  Through study completion for an average of 6 months

Study Arms (2)

Continuous AZD6738 & gemcitabine

EXPERIMENTAL

Intravenous gemcitabine on days 3, 10 and 17 of a 28 day cycle. Dose range from 500mg/m2 to 1000mg/m2. Oral tablet AZD6738 once daily for 21 days of a 28 day cycle. Dose range from 40mg to 120mg.

Drug: AZD6738; Drug: Gemcitabine

Intermittent AZD6738 & gemcitabine

EXPERIMENTAL

Intravenous gemcitabine on days 3, 10 and 17 of a 28 day cycle. Dose range from 500mg/m2 to 1000mg/m2. Oral tablet AZD6738 once daily and intermittently for up to 12 days of a 28 day cycle. Dose range from 40mg to 120mg.

Drug: AZD6738; Drug: Gemcitabine

Interventions

AZD6738 DRUG

A potent, selective inhibitor of the serine/threonine-specific protein kinase, ataxia telangiectasia and Rad3-related protein (ATR), with good selectivity against other phosphatidylinositol 3-kinase-related kinase (PIKK) family members.

Continuous AZD6738 & gemcitabine; Intermittent AZD6738 & gemcitabine

Gemcitabine DRUG

Nucleoside metabolic inhibitor.

Also known as: Gemzar

Continuous AZD6738 & gemcitabine; Intermittent AZD6738 & gemcitabine

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 (see section 11.13). 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.

You may not qualify if:

• 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 prior to start of trial treatment (greater than 5 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 prior to start of trial treatment.
• Immunotherapy within 42 days prior to start of trial treatment.
• New treatment with bisphosphonates or denosumab for bone metastases within 5 days prior to start of trial 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 prior to start of trial 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 prior to start of trial 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 5 half-lives, but three weeks for St. John's Wort, see Appendix 4). The use of herbal supplements, homeopathic remedies or 'folk remedies' is not permitted.
• Impaired hepatic or renal function defined as:
• AST or ALT \>2.5 x ULN (or 5 times if liver metastasis).
• Total bilirubin \>1.5 x ULN.

Sponsors & Collaborators

• CCTU- Cancer Theme: lead
• AstraZeneca: collaborator

Study Sites (1)

Cambridge University Hospitals NHS Foundation Trust

Cambridge, England, CB2 2QQ, United Kingdom

RECRUITING

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis

Interventions

ceralasertib; Gemcitabine

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Duncan Jodrell

  CRUK Cambridge Institute, University of Cambridge

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Early Phase Team, Cambridge Clinical Trials Unit - Cancer Theme

CONTACT

01223216083; cctuep@addenbrookes.nhs.uk

Cambridge Cancer Trials Centre, Coordination Team

CONTACT

01223216083; cctu.cancer@addenbrookes.nhs.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor Duncan Jodrell

Model Details: Continuous and intermittent administration schedule.

Study Record Dates

• First Submitted: August 7, 2018
• First Posted: September 13, 2018
• Study Start: October 15, 2019
• Primary Completion: September 30, 2023
• Study Completion: September 30, 2024
• Last Updated: June 4, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)