Durvalumab Plus Tremelimumab for the Treatment of Patients with Progressive, Refractory Advanced Thyroid Carcinoma -The DUTHY Trial

NCT ID: NCT03753919

Last Updated: 2024-11-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 79 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-02
• Study Completion Date: 2024-11-08

Brief Summary

This is a prospective, multi-centre, open label, stratified, exploratory phase II study evaluating the efficacy and safety of durvalumab plus tremelimumab in different cohorts of patients with thyroid cancers.

Conditions

Metastatic Thyroid Papillary Carcinoma; Metastatic Thyroid Follicular Carcinoma; Metastatic Thyroid Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Durvalumab + Tremelimumab

Durvalumab 1500 mg plus tremelimumab 75 mg every 4 weeks up to 4 cycles followed by durvalumab 1500 mg every 4 weeks until disease progression, unacceptable toxicity or patients' decision.

Group Type: EXPERIMENTAL

Durvalumab

Intervention Type: DRUG

Subjects will be allocated in each primary tumor cohort to receive durvalumab 1500 mg every 4 weeks (Q4W) plus tremelimumab 75 mg Q4W for up to 4 doses during the first 4 cycles of combined therapy. After the first 4 cycles (or before is tremelimumab is stopped due to toxicity), patients will continue to receive durvalumab 1500 mg Q4W until disease progression or unacceptable toxicity. Cycles are defined by 4 weeks or 28 days.

Tremelimumab

Intervention Type: DRUG

Subjects will be allocated in each primary tumor cohort to receive durvalumab 1500 mg every 4 weeks (Q4W) plus tremelimumab 75 mg Q4W for up to 4 doses during the first 4 cycles of combined therapy. After the first 4 cycles (or before is tremelimumab is stopped due to toxicity), patients will continue to receive durvalumab 1500 mg Q4W until disease progression or unacceptable toxicity. Cycles are defined by 4 weeks or 28 days.

Interventions

Durvalumab

Subjects will be allocated in each primary tumor cohort to receive durvalumab 1500 mg every 4 weeks (Q4W) plus tremelimumab 75 mg Q4W for up to 4 doses during the first 4 cycles of combined therapy. After the first 4 cycles (or before is tremelimumab is stopped due to toxicity), patients will continue to receive durvalumab 1500 mg Q4W until disease progression or unacceptable toxicity. Cycles are defined by 4 weeks or 28 days.

Intervention Type: DRUG

Tremelimumab

Subjects will be allocated in each primary tumor cohort to receive durvalumab 1500 mg every 4 weeks (Q4W) plus tremelimumab 75 mg Q4W for up to 4 doses during the first 4 cycles of combined therapy. After the first 4 cycles (or before is tremelimumab is stopped due to toxicity), patients will continue to receive durvalumab 1500 mg Q4W until disease progression or unacceptable toxicity. Cycles are defined by 4 weeks or 28 days.

Intervention Type: DRUG

Other Intervention Names

MEDI4736

Eligibility Criteria

Inclusion Criteria

• Written informed consent obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
• Age ≥ 18 years at time of study entry.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Body weight >30kg.
• Confirmed differentiated thyroid cancer (papillary, follicular, poorly differentiated and Hürtle cell), medullary thyroid cancer and anaplastic thyroid cancer.
• Available tumor and blood samples for translational research
• Patients should meet one of the following criteria:

3. Cohort 3: Patients with locally advanced or metastatic anaplastic thyroid cancer regardless of prior therapy. No prior therapy with immune check point inhibitors is allowed.

• No limitation of number of prior therapies.
• Life expectancy >3 months
• Adequate normal organ and marrow function as defined below: a) Haemoglobin ≥9.0 g/dL. b) Absolute neutrophil count (ANC) > 1500 per mm3. c) Platelet count ≥100,000 per mm3. d) Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician. e) AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal. f) Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance.
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre- menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: a) 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). b) 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).
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

• Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• History of allogenic organ transplantation.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], 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: a) Patients with vitiligo or alopecia. b) Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement. c) Any chronic skin condition that does not require systemic therapy. d) Patients without active disease in the last 5 years may be included but only after consultation with the study physician. e) Patients with celiac disease controlled by diet alone.
• 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: a) Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence. b) Adequately treated non-melanoma skin cancer or lentigomaligna without evidence of disease. c) Adequately treated carcinoma in situ without evidence of disease.
• 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.
• Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
• Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ highly effective birth control from screening to 90 days after the last dose of durvalumab monotherapy and 180 days for combined treatment with durvalumab and tremelimumab.
• Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
• Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements.

Exclusion Criteria

• Participation in another clinical study with an investigational product during the last 21 days.
• 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.
• Any previous treatment with a PD1, PD-L1 or CTLA-4 inhibitor, including durvalumab and tremelimumab.
• Any previous treatment with immunotherapy, including combinations of immunotherapy and other anticancer or targeted agents.
• Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction.
• Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. The following are exceptions to this criterion: a) Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection). b) Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent. c) Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

MFAR

OTHER

Sponsor Role: collaborator

Grupo Espanol de Tumores Neuroendocrinos

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jaume Capdevila, M.D., Ph.D.

Role: STUDY_CHAIR

Hospital Universitari Vall d'Hebron, Barcelona

Locations

Hospital Clínic Barcelona

Barcelona, Barcelona, Spain

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona, Spain

Instituto Catalán de Oncología de Hospitalet

L'Hospitalet de Llobregat, Barcelona, Spain

MD Anderson Cancer Center

Madrid, Madrid, Spain

Hospital Clínico San Carlos

Madrid, Madrid, Spain

Hospital Universitario 12 de Octubre

Madrid, Madrid, Spain

Hospital Universitario HM Sanchinarro

Madrid, Madrid, Spain

Hospital Universitario La Paz

Madrid, Madrid, Spain

Hospital Universitario Ramón y Cajal

Madrid, Madrid, Spain

Hospital General Universitario Morales Meseguer

Murcia, Murcia, Spain

Hospital Universitario Virgen de la Victoria

Málaga, Málaga, Spain

Clínica Universidad de Navarra

Pamplona, Pamplona, Spain

Complejo Hospitalario Universitario de Vigo (CHUVI)

Vigo, Spain, Spain

Hospital Provincial de Castellón

Castellon, Valencia, Spain

Instituto Valenciano de Oncología

Valencia, Valencia, Spain

Countries

Spain

Other Identifiers

2018-001066-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GETNE-T1812

Identifier Type: -

Identifier Source: org_study_id