- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03473574
Durvalumab and Tremelimumab With Gemcitabine or Gemcitabine/Cisplatin Compared to Gemcitabine/Cisplatin in CCA Patients (IMMUCHEC)
A Randomized Phase II Trial of Durvalumab and Tremelimumab With Gemcitabine or Gemcitabine and Cisplatin Compared to Gemcitabine and Cisplatin in Treatment-naïve Patients With Cholangio- and Gallbladder Carcinoma (IMMUCHEC)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Hannover, Germany, 30625
- Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie & Endokrinologie
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Fully-informed written consent and locally required authorization (European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
- Age ≥ 18 years.
- Histologically documented diagnosis of cholangiocarcinoma or gall bladder carcinoma and available tumor tissue (block or at least 4 slides) for translational research.
- Performance status (PS) ≤ 1(ECOG scale).
- At least one measurable site of disease as defined by RECISTv1.1 criteria.
Adequate bone marrow and renal function including the following: Hemoglobin
≥ 9.0 g/dL; absolute neutrophil count ≥ 1.5 x 10^9/L; platelets ≥ 100 x 10^9 /L; Creatinine ≤ 1.5 x upper normal limit.
- Calculated creatinine clearance ≥40 mL/min as determined by the Cockcroft- Gault equation (using actual body weight)
- Adequate hepatic function (with stenting for any obstruction, if required) including the following: Total bilirubin ≤ 2x upper normal limit; AST (SGOT), ALT (SGPT) ≤ 5 x upper normal limit; prothrombin time ≥ 60%; albumin ≥ 30 g/L.
- Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.
Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered postmenopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
- Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
- Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
- The patient is willing and able to comply with the protocol for the duration of the study, including hospital visits for treatment and scheduled follow-up visits and examinations.
Exclusion Criteria:
- Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study, or during the follow-up period of an interventional study
- Participation in another clinical study with an investigational product within 21 days prior to the first dose of the study treatment.
- Prior immunotherapy or use of other investigational agents, including prior treatment with an anti-Programmed Death receptor-1 (PD-1), anti-Programmed Death-1 ligand-1 (PD-L1), anti-PD-L2, or anti-cytotoxic T-lymphocyte associated antigen-4 (anti-CTLA-4) antibody, therapeutic cancer vaccines.
- Prior chemotherapy with gemcitabine, Cisplatin and/or capecitabine (exception: gemcitabine, cisplatind and/or capecitabine in the adjuvant setting, last infusion has to be ≥ 6 months prior randomization).
Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
- Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
- Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician.
- Any concurrent chemotherapy, IMP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable. Note: Local treatment of isolated lesions for palliative intent is acceptable (eg, local radiotherapy).
- Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drugs.
- Major surgery (as defined by the Investigator) within 4 weeks prior to the first dose of the investigational product (IMP) of starting the study and patients must have recovered from effects of major surgery. Note: Local non-major surgery for palliative intent (eg, surgery of isolated lesions, per-cutaneous biliary drainage or biliary stenting) is acceptable.
- History of allogenic organ transplantation.
Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], celiac disease, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]).
The following are exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
- Any chronic skin condition that does not require systemic therapy
- Patients without active disease in the last 5 years may be included but only after consultation with the study physician
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
History of another primary malignancy except for:
- Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IMP and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated carcinoma in situ without evidence of disease
- History of leptomeningeal carcinomatosis
- Brain metastases or spinal cord compression. Patients with suspected brain metastases at screening should have a CT/ MRI of the brain prior to study entry.
- History of active primary immunodeficiency
- Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen [HBsAg) result], hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection)
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication) Receipt of live attenuated vaccine within 30 days prior to the first dose of IMP.
Note: Patients, if enrolled, should not receive live vaccine whilst receiving IMP and up to 30 days after the last dose of IMP. 19. Body weight ≤30 kg. 20. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of tremelimumab monotherapy or 180 days after the last dose of durvalumab + tremelimumab combination therapy. 21. Known allergy or hypersensitivity to any of the IMPs or any of the constituents of the product. 22. Prior randomisation or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment. 23. Any co-existing medical condition that in the investigator's judgement will substantially increase the risk associated with the patient's participation in the study. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG. 25. Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG].
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Arm A
Durvalumab in combination with Tremelimumab (Regimen 1) and Gemcitabine
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immune checkpoint inhibitor
standard chemotherapy
immune checkpoint inhibitor
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Experimental: Arm B
Durvalumab in combination with Tremelimumab (Regimen 1), Gemcitabine and Cisplatin
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immune checkpoint inhibitor
standard chemotherapy
immune checkpoint inhibitor
standard chemotherapy
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Other: Arm C
Gemcitabine in combination with Cisplatin
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standard chemotherapy
standard chemotherapy
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Experimental: Arm D
Durvalumab in combination with Tremelimumab (Regimen 2), Gemcitabine and Cisplatin
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immune checkpoint inhibitor
standard chemotherapy
immune checkpoint inhibitor
standard chemotherapy
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Experimental: Arm E
Durvalumab in combination with Gemcitabine and Cisplatin
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immune checkpoint inhibitor
standard chemotherapy
standard chemotherapy
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response rate (ORR)
Time Frame: 30 months
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Response Rate (RR) according to RECIST V1.1
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30 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival (OS)
Time Frame: max observation period 30 months
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Efficacy of the combination of durvalumab and tremelimumab in addition with gemcitabine or in addition with gemcitabine and cisplatin in treatment naïve patients with advanced, unresectable and/or metastatic cholangio- and gallbladder carcinoma
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max observation period 30 months
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Incidence of Treatment Emergent Adverse Events as assessed by NCI CTCAE V4.0 (Safety and Tolerability)
Time Frame: 30 months
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Data will be obtained on vital signs, clinical parameters and feasibility of the regimen
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30 months
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Quality of Life
Time Frame: 30 months
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EORTC-QLQ-C30 (European Organisation for Research and Treatment of Cancer - Quality of Life Core Questionnaire 30 items) Version 3.0.
The QLQ-C30 is composed of multi-item scales and single-item measures, including fiveAll of the scales and single-item measures have a score range from 0 to 100.
A high score shows a high response level.
A high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems functional scales, three symptom scales, a global health status / QoL scale, and six single items.
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30 months
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Arndt Vogel, Prof. Dr., Hannover Medical School
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Urologic Diseases
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Urinary Bladder Diseases
- Digestive System Neoplasms
- Gallbladder Diseases
- Biliary Tract Diseases
- Biliary Tract Neoplasms
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Carcinoma
- Urinary Bladder Neoplasms
- Cholangiocarcinoma
- Gallbladder Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Durvalumab
- Tremelimumab
- Gemcitabine
Other Study ID Numbers
- AIO-HEP-0117
- 2017-001538-25 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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