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CancerPhase 1ATRiUMNCT03669601

AZD6738 & Gemcitabine as Combination Therapy

A Phase 1 study testing AZD6738 and Gemcitabine in people with Cancer, run by CCTU- Cancer Theme at 1 site in United Kingdom.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

A dose escalation trial to assess the safety of AZD6738 in combination with gemcitabine in participants with advanced solid tumours. Read more about this study

Who is it for?
Ages 16 years and older
Conditions the study is for
Cancer
What is being tested?
AZD6738 and Gemcitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
55 participants
Where
1 siteUnited Kingdom
Study dates
15 Oct 2019to 30 Sep 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • Glomerular filtration rate (GFR) (calculated by Cockcroft-Gault) of <41 ml/min.
  • Inadequate bone marrow reserve or organ function defined as:
  • Absolute neutrophil count <1.5 x 109/L.
  • Platelet count <100 x 109/L with no blood transfusions in the past 28 days.
  • 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:
  • Myocardial infarction
  • NYHA Class II/III/IV heart failure
  • Unstable angina pectoris
  • 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:
  • 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 Fridericia formula.
  • Patients with relative hypotension (<90/60 mm Hg) or clinically relevant orthostatic hypotension, including a fall in blood pressure of > 20 mmHg.
  • Patients at risk of brain perfusion problems (e.g. medical history of carotid stenosis, pre-syncope, syncope episodes or a history of transient ischaemic attack).
  • Uncontrolled hypertension (grade 2 or above) requiring clinical intervention.
  • Patients unable to swallow orally administered medication and with gastrointestinal disorders likely to interfere with absorption of AZD6738.
  • Any other concurrent severe and/or uncontrolled medical condition that places the patient at unacceptable risk of toxicity or non-compliance (examples include, but are not limited to, active bleeding diatheses, renal transplant, uncontrolled major seizure disorder, severe COPD, superior vena cava syndrome, extensive bilateral lung disease on high resolution CT scan, severe Parkinson's disease, active inflammatory bowel disease, psychiatric condition, or active infection (including any patient known to have hepatitis B, hepatitis C, human immunodeficiency virus (HIV) or requiring systemic antibiotics, antifungals or antiviral drugs)). Screening for chronic conditions is not required.
  • Prior exposure to an ATR inhibitor.
  • A known hypersensitivity to AZD6738 or gemcitabine (e.g. excessive myelosuppression), any excipient of the products, or any contraindication to the combination of anti-cancer agents.
  • Any unresolved toxicities from prior therapy of CTCAE grade >1 (with the exception of alopecia and CTCAE grade 2 neuropathy).
  • Spinal cord compression (unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of treatment).
  • Brain metastases (unless disease outside the central nervous system (CNS) is present, no clinical evidence of progression since completion of CNS-directed therapy, at least 3 weeks between completion of radiotherapy and start of trial treatment, recovery from significant (Grade ≥ 3) acute toxicity) with no on-going requirement for >10 mg of prednisone per day or an equivalent dose of other corticosteroid. If on corticosteroids, the patient should be receiving a stable dose of corticosteroids started at least 4 weeks prior to treatment).
  • Judgment by the Investigator that the patient should not participate in the trial.

Trial locations and contacts

1 site in 1 country.

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

United Kingdom1 site, 1 recruiting

  • Cambridge University Hospitals NHS Foundation Trust

    Cambridge, England, CB2 2QQ

    Recruiting

Other trials in United Kingdom

About this study

Official title: A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of Ascending Doses of Combined Therapy With ATR Inhibitor AZD6738 and Gemcitabine, Using a Model Based Design.

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

Read the detailed description

A phase 1, non-randomised, multicentre, model-based dose escalation trial. This trial will assess the safety, tolerability, pharmacokinetics and preliminary anti-tumour activity of ascending doses of combined therapy with ATR inhibitor (AZD6738) and gemcitabine, in participants with advanced solid tumours, followed by an expansion phase in participants with advanced pancreatic ductal adenocarcinoma (PDAC).

Conditions
Cancer
Being tested
AZD6738, Gemcitabine
Keywords
solid tumour, locally advanced, metastatic
Medical subject headings
Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AZD6738Drug

    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.

  • GemcitabineDrug

    Also called Gemzar

    Nucleoside metabolic inhibitor.

Study groups in NCT03669601
Study groupRoleWhat they receive
Continuous AZD6738 & gemcitabineExperimentalIntravenous 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.
Receives: Drug: AZD6738; Drug: Gemcitabine
Intermittent AZD6738 & gemcitabineExperimentalIntravenous 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.
Receives: Drug: AZD6738; Drug: Gemcitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: Through study completion

Secondary outcomes (1)

  1. Evaluate anti-tumour effect

    CT scan tumour measurement assessments from start of treatment until progression

    Measured: Through study completion for an average of 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Sep 2018
  2. Study start15 Oct 2019
  3. Primary completion30 Sep 2023 (estimated)
  4. Study completion30 Sep 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Continuous and intermittent administration schedule.
Masking
None (open label)
Enrolment
55 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03669601
Sponsor's protocol ID
ATRiUM
Acronym
ATRiUM
Status last verified
Jun 2021
First submitted
7 Aug 2018
Last updated
4 Jun 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AZD6738 and Gemcitabine in people with Cancer, run by CCTU- Cancer Theme at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 4 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Early Phase Team, Cambridge Clinical Trials Unit - Cancer Theme (01223216083, cctuep@addenbrookes.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicity for the combination of AZD6738 and gemcitabine. (time frame: Through study completion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03669601.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2021.

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AZD6738 & Gemcitabine as Combination Therapy | AzTrials