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

NCT03753919 | Terminated Phase 2 Results DMC

• 2 other identifiers: GETNE-T18122018-001066-42
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 15

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

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival Rate at 6 Months

  6-months progression-free survival by Response Evaluation Criteria in Solid Tumors (RECIST v1.1), which is defined as the percentage of patients achieving complete response (CR), partial response (PR), or stable disease (SD) at 24 weeks after durvalumab plus tremelimumab was started without observing disease progression or death at this time point. Per RECIST for target lesions, CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progression disease. For non-target lesions, CR: Disappearance of all non-target lesions; Non-CR/Non-PD: Persistence of one or more non-target lesion(s).

  Throughout the study period, up to 6 months from start of treatment

• Overall Survival Rate at 6 Months

  Defined as percentage of patients alive at month 6 from first dose of treatment.

  Throughout the trial period, up to 6 months from first dose of treatment.

Secondary Outcomes (10)

• Overall Survival, Median

  Throughout the trial period, with a following up to 4 years from the start of treatment

• Overall Survival Rate at 18 Months

  Throughout the trial period, up to 18 months from first dose of treatment.

• Progression-free Survival (PFS), Median

  Throughout the trial period, a median follow-up period 14 months from the start of treatment

• Progression-free Survival Rate at 18 Months

  Throughout the study period, up to 18 months from start of treatment

• Overall Response Rate (ORR)

  Through study completion, average 1 year

Study Arms (1)

Durvalumab + Tremelimumab

EXPERIMENTAL

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.

Drug: Durvalumab; Drug: Tremelimumab

Interventions

Durvalumab 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.

Also known as: MEDI4736

Durvalumab + Tremelimumab

Tremelimumab 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.

Durvalumab + Tremelimumab

Eligibility Criteria

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

You may qualify if:

• 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 Hürthle cell), medullary thyroid cancer and anaplastic thyroid cancer.
• Available tumor and blood samples for translational research
• Patients should meet one of the following criteria:
• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Grupo Espanol de Tumores Neuroendocrinos: lead
• MFAR: collaborator

Study Sites (15)

Instituto Catalán de Oncología de Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Provincial de Castellón

Castellon, Valencia, Spain

Location

Hospital Clínic Barcelona

Barcelona, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

MD Anderson Cancer Center

Madrid, 28033, Spain

Location

Hospital Clínico San Carlos

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario HM Sanchinarro

Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, Spain

Location

Hospital General Universitario Morales Meseguer

Murcia, Spain

Location

Clínica Universidad de Navarra

Pamplona, Spain

Location

Instituto Valenciano de Oncología

Valencia, 46009, Spain

Location

Complejo Hospitalario Universitario de Vigo (CHUVI)

Vigo, 36036, Spain

Location

MeSH Terms

Conditions

Thyroid Cancer, Papillary; Adenocarcinoma, Follicular; Thyroid Neoplasms

Interventions

durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

Adenocarcinoma, Papillary; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Results Point of Contact

• Title: Clinical Research Manager
• Organization: MFAR

investigacion@mfar.net

934344412

Study Officials

• Jaume Capdevila, M.D., Ph.D.

  Hospital Universitari Vall d'Hebron, Barcelona

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Model Details: * Cohort 1: Advanced, radioiodine-refractory differentiated thyroid carcinoma, including papillary, follicular, Hürthle Cell and poorly-differentiated thyroid carcinoma (DTC). * Cohort 2: Advanced medullary thyroid carcinoma (MTC). * Cohort 3: Advanced anaplastic thyroid cancer (ATC).

Study Record Dates

• First Submitted: November 20, 2018
• First Posted: November 27, 2018
• Study Start: April 2, 2019
• Primary Completion: November 8, 2024
• Study Completion: November 8, 2024
• Last Updated: March 11, 2026
• Results First Posted: March 11, 2026

Record last verified: 2026-03

Locations

ES (15)