AzTrials
AzTrials

Esophageal CancerPhase 2DYNAMICNCT03818997

Combination of Targeted and Immunotherapy for Advanced Biliary Tract and Esophagogastric Gastric Cancer

A Phase 2 study testing DKN-01, Atezolizumab and Paclitaxel in people with Esophageal Cancer and Biliary Tract Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

In this study, non-operable esophagogastric adenocarcinoma cancer patients or non-operable biliary cancer patients whose cancer progressed/spread/got worse after first line treatment will be treated with or without immunotherapy and chemotherapy. This study will take place in several countries across Europe. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
DKN-01, Atezolizumab and Paclitaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Dec 2019to Apr 2022
Phase
Phase 2
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically proven diagnosis of metastatic or locally unresectable adenocarcinoma of the biliary tract or esophagogastric adenocarcinoma.
  • Measurable disease by CT/MRI (RECIST 1.1) within 28 days of randomization/enrollment
  • Male and female subjects of age ≥18 years
  • Performance status ECOG 0-1
  • Life expectancy ≥ 4 months
  • Normal 12-lead ECG (patients with abnormal ECG will be eligible if changes are not considered clinically significant by the local investigator)
Show all 50Show fewer
  • Adequate hematological function
  • Hemoglobin ≥ 9 g/dl (prior transfusions are allowed if they have been done ≥ 7 days before testing the Hb)
  • White blood cell (WBC) ≥ 3.0 x 109/L
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
  • Platelet count ≥ 75 x 109/L
  • Adequate liver function: screening labs should be performed within 7 days prior to randomization/enrollment:
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN), except subjects with Gilbert Syndrome who must have a total bilirubin level of < 3.0 x ULN.
  • ALT, AST \& alkaline phosphatase ≤ 3 x ULN; ≤ 5 x ULN in case of liver/bone metastases
  • Serum albumin ≥ 2.5 g/dL
  • Adequate renal function:
  • o Estimated glomerular filtration rate (eGFR) according to MDRD should be > 50 ml/min
  • Adequate coagulation:
  • o International Normalized Ratio (INR) or Prothrombin Time (PT): ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or Partial Thromboplastin Time (PTT) is within therapeutic range of intended use of anticoagulants
  • The following local treatment modalities are allowed within the rules described (provided there has been a full recovery):
  • Surgery: patients may have undergone a non-curative operation (i.e. R2 resection [with macroscopic residual disease] or palliative bypass surgery only), performed at least 28 days before randomization/enrollment. Patients who have previously undergone curative surgery, must have evidence of non-resectable and measurable disease relapse requiring systemic chemotherapy prior to study entry.
  • Radiotherapy: patients may have received prior radiotherapy (with or without radiosensitising low-dose chemotherapy) for localised disease. However, there must be clear evidence of disease progression post-treatment prior to inclusion in this study. The radiotherapy should have been finished at least 15 days prior to randomization/enrollment.
  • Photodynamic therapy (PDT) for localized disease only with no evidence of metastatic disease - patients may have received prior PDT, provided the patient has fully recovered and at least 28 days have elapsed since the PDT and there is clear evidence of disease progression at the local site or disease or at a new metastatic site.
  • Other previous localised treatments targeting intrahepatic lesions such as selective internal radiation therapy (SIRT), transarterial chemoembolisation (TACE) and radiofrequency ablation are allowed, provided the patient has finished it at leas 15 days prior to randomization/enrollment, with recovering.
  • Asymptomatic subjects with known Central Nervous system (CNS) metastases are eligible, provided that all of the following criteria are met:
  • Measurable disease, per RECIST v1.1, must be present outside the CNS.
  • The patient has no history of intracranial hemorrhage or spinal cord hemorrhage.
  • The patient has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment.
  • The patient has no ongoing requirement for corticosteroids as therapy for CNS disease. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to enrollment /randomization.
  • Any brain metastases must be stable for at least 6 months.
  • Availability of 1 FFPE block (preferred) or if not available, minimum 15-20 freshly cut (≤ 7 days) unstained slides of tumor tissue (either from current or previous resection/biopsy) for biobanking/translational research if less tumor tissue available please contact the HQ study team.
  • Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test within 72 hours prior to the first dose of study treatment.
  • Patients of childbearing / reproductive potential should use adequate birth control measures and agree to refrain from donating eggs, according the standard national guidelines during the study treatment period and for at least 6 months after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly. Such methods include:
  • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
  • Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
  • Intrauterine device (IUD)
  • Intrauterine hormone-releasing system (IUS)
  • Bilateral tubal occlusion
  • Vasectomised partner
  • Sexual abstinence. Note: abstinence is acceptable if this is established and preferred contraception for the patient and is accepted as a local standard.
  • Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment.
  • Before patient enrollment, written informed consent must be given according to ICH/GCP, and national/local regulations.
  • Specific to BTC:
  • Patients should have progressed after first line systemic therapy.
  • If clinically indicated, adequate biliary drainage should have been performed, patient should have fully recovered.
  • Specific to advanced EGC:
  • •Patients who have progressed after first line therapy. HER2 positive patient should have received and progressed on trastuzumab therapy. In HER2 positive patient, neo/adjuvant therapy based on a platinum and a fluoropyrimidine could be considered a first line of therapy if the patient progressed within the first 3 months of completing it.
  • Note: patients who have undergone palliative treatment for obstruction or bleeding maybe eligible as long as they fulfill the above mentioned hematologic and biochemistry criteria.
  • Weight must be stabilized in the last 4 weeks , as assessed by the investigator
  • Taxanes, such as paclitaxel or docetaxel are only allowed in the curative setting (perioperative treatment) if received at least 12 months before enrollment/randomization.

Who cannot join

  • Subjects with pleural effusion, pericardial effusion, or ascites with symptoms uncontrolled by medication or who requirere current drainage procedures (once monthly or more frequently).
  • Leptomeningeal spread of disease.
  • Patient is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks prior to enrollment
  • Other concomitant or prior malignancy within the last 5 years, with the exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix.
  • History of inflammatory bowel disease or any autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, type I diabetes mellitus, vasculitis, or glomerulonephritis
  • Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible for this study.
Show all 41Show fewer
  • Patients with controlled Type I diabetes mellitus on a stable insulin regimen are eligible.
  • Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
  • Rash must cover less than 10% of body surface area.
  • Disease is well controlled at baseline and requires only low-potency topical corticosteroids.
  • Occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months.
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
  • History of radiation pneumonitis/fibrosis in the radiation field is permitted.
  • Infections:
  • Signs or symptoms of infection or therapeutic use of antibiotics (except prophylactic antibiotics) within 2 weeks prior to randomization and severe infections within 4 weeks prior to randomization, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
  • Known or current evidence of HIV (test to be performed within 14 days of randomization)
  • Active or chronic hepatitis B or hepatitis C
  • Patients with past/resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. HBV DNA must be obtained in patients with positive hepatitis B core antibody prior to randomization.
  • Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
  • Active tuberculosis
  • Conditions leading to immune suppression or stimulation of the immune system, such as:
  • Prior treatment with checkpoint inhibitors
  • Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided at least 5 half-lives (approximately 75 days) have elapsed since the last dose of anti-CTLA-4 and there was no history of severe immune-mediated adverse effects from anti-CTLA-4 (NCI CTCAE Grade 3 or 4)
  • Treatment with systemic immunostimulatory agents (including but not limited to IFN-a, IL-2) for any reason within 6 weeks or five half-lives of the drug, whichever is shorter, prior to enrollment.
  • Prior allogeneic stem cell or solid organ transplant.
  • Subjects with a condition requiring systemic treatment with either corticosteroids (≥ 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of randomization/enrollment
  • Prior treatment with an anti-DKK1 therapy
  • Administration of a live, attenuated vaccine within 30 days prior to the first dose of study medication or anticipation that such a live attenuated vaccine will be required during the study. Any live, attenuated vaccine (e.g. FluMist®) is prohibited while the patient is receiving atezolizumab and for a period of 5 months after discontinuation of atezolizumab. Inactivated influenza vaccines are allowed only during flu season.
  • History of osteonecrosis of the hip or evidence of structural bone abnormalities in the proximal femur on magnetic resonance imaging (MRI) scan that is symptomatic and clinically significant. Degenerative changes of the hip joint are not excluded.
  • All non hematological toxicities attributed to prior anti-cancer therapy other than hearing loss, alopecia and fatigue must have resolved to Grade 1 (NCI CTCAE version 5) or baseline before administration of study drug.
  • History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal products.
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein; known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
  • Uncontrolled tumor-related pain.
  • Uncontrolled or symptomatic hypercalcemia (ionized calcium 1.5 mmol/L, calcium 12 mg/dL or corrected serum calcium ULN)
  • Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident), unstable arrhythmia, or unstable angina within 3 months prior to initiation of study treatment.
  • Specific to BTC:
  • Ampullary or gallbladder carcinoma
  • Patients with liver failure Child-Pugh B or C
  • Specific to EGC:
  • History of hypersensitivity reactions to paclitaxel or other drugs formulated in Cremophor EL (polyoxyethylated castor oil)

About this study

Official title: DKN-01/Atezolizumab as Second Line Treatment of biliarY Tract Cancer and in combiNAtion or Not With Paclitaxel as Second Line treatMent of esophagogastrIC Cancer: a Multi-center Phase II Trial

In this study, non-operable esophagogastric adenocarcinoma cancer patients or non-operable biliary cancer patients whose cancer progressed/spread/got worse after first line treatment will be treated with or without immunotherapy and chemotherapy. This study will take place in several countries across Europe. One hundred twenty-three (123) patients will be invited to participate in this study

Biliary tract cancer (BTC), is a form of cancer that start in your bile ducts, a series of tubes that runs from the liver to the small intestines. It is not know yet the exact cause of BTC. For patients who have advanced or metastatic BTC (where surgery is not possible), chemotherapy is the first option for treatment. Chemotherapy with cisplatin and gemcitabine (CisGem) is the current standard of care.

Read more

Esophagogastric cancer (EGC) is cancer that occurs in the esophagus, a long hollow tube that runs from your throat to your stomach. The accumulating abnormal cells form a tumor in the esophagus that can grow to invade nearby structures and spread to other parts of the body. It's thought that chronic irritation of your esophagus may contribute to the changes that cause esophageal cancer.

The purpose of this study is to look at the risks and benefits of combining DKN-01 and atezolizumab (humanized monoclonal antibody) with or without paclitaxel (chemotherapy). Immune therapy boosts the body's natural defenses to fight cancer. It uses specific products made either by participants' body or in a laboratory to improve, target or restore immune system function and control or stop cancer. Atezolizumab is such an "immunotherapy" drug. DKN-01 is another new type of drug (humanized monoclonal antibody) in development as anticancer agent. Paclitaxel is a commonly-used chemotherapy drug of the class of taxanes used to treat a number of cancer types, it stimulates the cell to die or to stop the cell from dividing into two new cells.The idea behind combining these drugs is linked to targeting the immune system to attack the tumor. Combining immune and chemotherapy has already demonstrated clinical activity in relapsed (return of the disease)/refractory (not responding to treatment) esophagogastric cancer patients.

Being tested
DKN-01, Atezolizumab, Paclitaxel
Medical subject headings
Esophageal Neoplasms, Biliary Tract Neoplasms

What participants receive

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

  • DKN-01Drug

    Patient will receive DKN-01 300 mg IV every 2 weeks

  • AtezolizumabDrug

    Also called Tecentriq

    Patient will receive Atezolizumab 840 mg IV every 2 weeks until PD

  • PaclitaxelDrug

    Patient will receive Paclitaxel 80 mg/m2 IV on day 1, 8 and 15 of a 28 day cycle until PD

Study groups in NCT03818997
Study groupRoleWhat they receive
BTC CohortExperimentalPatient in BTC cohort will receive immune therapy and DKN-01 IV until PD
Receives: Drug: DKN-01; Drug: Atezolizumab
EGC cohort: DKN-01/atezolizumab + paclitaxel (Arm 1)ExperimentalPatient randomized in the EGC Arm 1 will receive immune therapy, DKN-01 and chemotherapy intravenously (IV) until PD.
Receives: Drug: DKN-01; Drug: Atezolizumab; Drug: Paclitaxel
EGC cohort: DKN-01/atezolizumab without paclitaxel (Arm 2)ExperimentalPatient randomized in the EGC Arm 2 will receive immune therapy and DKN-01 IV until PD
Receives: Drug: DKN-01; Drug: Atezolizumab

What is being measured

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

  1. Objective response rate

    Objective response rate according to RECIST v1.1 is computed as the rate of complete and partial responses (with response confirmation)

    Measured: 6 months from start of study treatment

Secondary outcomes (7)

  1. Best overall response distribution

    According to RECIST1.1 and iRECIST

    Measured: 6 months from start of study treatment

  2. Immune objective response rate according to iRECIST

    Immune objective response rate according to iRECIST is computed as the rate of immune complete and partial responses (with response confirmation)

    Measured: 6 months from start of study treatment

  3. Duration of response using RECIST 1.1 and iRECIST

    Response duration will be measured from the time measurement criteria for CR/PR or iCR/iPR are first met until the first date that recurrent or progressive disease is objectively documented, taking as reference the smallest measurements recorded on study (including baseline).

    Measured: Until 2 years after start of study treatment

  4. Progression free survival according to RECIST 1.1 and iRECIST

    Progression free survival (PFS) according to RECIST 1.1 and iRECIST is defined as the number of days from date of start of treatment to the date of first progression according to RECIST 1.1 or iRECIST respectively or death, whatever comes first. Patients alive and free of progression prior to the analysis cut-off date are censored at the date of the most recent assessment.

    Measured: Until 2 years after start of study treatment

  5. Occurrence of adverse events

    The study uses the International Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, for adverse event reporting

    Measured: Until 2 years after start of study treatment

  6. Overall survival (OS)

    Overall Survival is defined as the number of days from date of start of treatment to the date of death due to any cause. If a patient has not died, the data will be censored at the last date documented to be alive

    Measured: Until 2 years after start of study treatment

  7. Duration of stable disease using RECIST 1.1 and iRECIST

    Stable disease duration will be measured from the time of start of treatment until the criteria for progression are met, taking as reference the smallest sum on study (including baseline)

    Measured: Until 2 years after start of study treatment

Timeline

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

  1. First posted28 Jan 2019
  2. Study startDec 2019 (estimated)
  3. Primary completionApr 2021 (estimated)
  4. Study completionApr 2022 (estimated)

Why it stopped: Company decision

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03818997
Sponsor's protocol ID
EORTC 1741-GITCG
Acronym
DYNAMIC
Status last verified
Feb 2020
First submitted
24 Jan 2019
Last updated
5 Feb 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing DKN-01, Atezolizumab and Paclitaxel in people with Esophageal Cancer and Biliary Tract Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC.

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 50 inclusion and 41 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: withdrawn, as of the sponsor's last update on 5 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (time frame: 6 months from start of study treatment). 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 NCT03818997.

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 5 Feb 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in