Durvalumab and Tremelimumab With Gemcitabine or Gemcitabine/Cisplatin Compared to Gemcitabine/Cisplatin in CCA Patients

NCT03473574 | Completed Phase 2 DMC

• 2 other identifiers: AIO-HEP-01172017-001538-25
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

Brief Summary

To determine the efficacy in terms of objective response rate (ORR) 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 (CCA).

Conditions

Cholangiocarcinoma; Gall Bladder Carcinoma; Cholangiocarcinoma Non-resectable; Gallbladder Carcinoma Non-Resectable

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  Response Rate (RR) according to RECIST V1.1

  30 months

Secondary Outcomes (3)

• Overall survival (OS)

  max observation period 30 months

• Incidence of Treatment Emergent Adverse Events as assessed by NCI CTCAE V4.0 (Safety and Tolerability)

  30 months

• Quality of Life

  30 months

Study Arms (5)

Arm A

EXPERIMENTAL

Durvalumab in combination with Tremelimumab (Regimen 1) and Gemcitabine

Biological: Durvalumab; Drug: Gemcitabine; Biological: Tremelimumab

Arm B

EXPERIMENTAL

Durvalumab in combination with Tremelimumab (Regimen 1), Gemcitabine and Cisplatin

Biological: Durvalumab; Drug: Gemcitabine; Drug: Cisplatin; Biological: Tremelimumab

Arm C

OTHER

Gemcitabine in combination with Cisplatin

Drug: Gemcitabine; Drug: Cisplatin

Arm D

EXPERIMENTAL

Durvalumab in combination with Tremelimumab (Regimen 2), Gemcitabine and Cisplatin

Biological: Durvalumab; Drug: Gemcitabine; Drug: Cisplatin; Biological: Tremelimumab

Arm E

EXPERIMENTAL

Durvalumab in combination with Gemcitabine and Cisplatin

Biological: Durvalumab; Drug: Gemcitabine; Drug: Cisplatin

Interventions

Durvalumab BIOLOGICAL

immune checkpoint inhibitor

Arm A; Arm B; Arm D; Arm E

Gemcitabine DRUG

standard chemotherapy

Arm A; Arm B; Arm C; Arm D; Arm E

Cisplatin DRUG

standard chemotherapy

Arm B; Arm C; Arm D; Arm E

Tremelimumab BIOLOGICAL

immune checkpoint inhibitor

Arm A; Arm B; Arm D

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead
• AstraZeneca: collaborator

Study Sites (1)

Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie & Endokrinologie

Hanover, 30625, Germany

Location

Related Links

• AIO - Working Group for Medical Oncology from the German Cancer Society
• Description AIO-Studien-gGmbH

MeSH Terms

Conditions

Cholangiocarcinoma; Gallbladder Neoplasms

Interventions

durvalumab; Gemcitabine; Cisplatin; tremelimumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Biliary Tract Diseases; Digestive System Diseases; Gallbladder Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Arndt Vogel, Prof. Dr.

  Hannover Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Treatment Arm A: Combination of Durvalumab, Tremelimumab (Regimen 1) and Gemcitabine Treatment Arm B: Combination of Durvalumab, Tremelimumab (Regimen 1), Gemcitabine and Cisplatin Treatment Arm C: Gemcitabine and Cisplatin Treatment Arm D: Combination of Durvalumab, Tremelimumab (Regimen 2), Gemcitabine and Cisplatin Treatment Arm E: Combination of Durvalumab, Gemcitabine and Cisplatin

Study Record Dates

• First Submitted: March 14, 2018
• First Posted: March 22, 2018
• Study Start: May 2, 2018
• Primary Completion: March 15, 2022
• Study Completion: March 15, 2022
• Last Updated: June 15, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)