Durvalumab plus tremelimumab for progressive, refractory advanced thyroid carcinoma

Phase 1

• Conditions: Advanced, radioiodine-refractory differentiated thyroid carcinoma, including papillary,follicular, Hürtle Cell and poorly-differentiated thyroid carcinoma (DTC).Advanced medullary thyroid carcinoma (MTC)Advanced anaplastic thyroid cancer (ATC); MedDRA version: 20.0Level: PTClassification code 10076603Term: Poorly differentiated thyroid carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10002240Term: Anaplastic thyroid cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.1Level: PTClassification code 10016935Term: Follicular thyroid cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10027105Term: Medullary thyroid cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10033701Term: Papillary thyroid cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.1Level: PTClassification code 10071027Term: Thyroid cancer stage ISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.1Level: PTClassification code 10071028Term: Thyroid cancer stage IISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-001066-42-ES
• Lead Sponsor: Spanish Group of Neuroendocrine Tumors (GETNE)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-11-23
• Last Update Posted: 3 November 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 84

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 1Body weight >30kg.
? Confirmed differentiated thyroid cancer (papillary, follicular, poorly differentiated and Hürtle cell), medullary thyroid cancer or anaplastic thyroid cancer.Available tumor and blood samples for translational research.
? Patients should meet one of the following criteria:
o Cohort 1: Patients with locally advanced or metastatic differentiated thyroid cancer (including the subtypes of papillary, follicular, poorly differentiated and Hürthle cell carcinoma) after disease progression on systemic therapy with MKIs. Patients could be recruited in the study after progression on Lenvatinib (regardless prior lines) or progression on at least two prior MKIs which may or not include Lenvatinib. No prior therapy with immune check point inhibitors is allowed.
Patients with intolerable toxicity to MKIs that meet the prior inclusion criteria and experience disease progression by RECIST v1.1 after stopping therapy may be included.
o Cohort 2: Patients with locally advanced or metastatic medullary thyroid cancer after progression on systemic therapy with MKIs. Patients could be recruited in the study after progression to Vandetanib (regardless prior lines) or progression to at least two prior MKIs that may or not include Vandetanib. No prior therapy with immune check point inhibitors is allowed. Patients with intolerable toxicity to MKIs that meet the prior inclusion criteria and experience disease progression by RECIST v1.1 after
stopping therapy may be included.
o 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:
? Haemoglobin =9.0 g/dL.
? Absolute neutrophil count (ANC) > 1500 per mm 3 .
? Platelet count =100,000 per mm 3 .
? 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.
? AST (SGOT)/ALT (SGPT) =2.5 x institutional upper limit of normal.
? Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40 mL/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:
o 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).
o Women =50 years of age would be considered post-meno

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, except for intranasal and inhaled corticosteroids or systemic at physiological doses (<10 mg/day of prednisone, or an equivalent). Exceptions:
o Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection).
o Systemic corticosteroids at physiologic doses <10 mg/day of prednisone or its equivalent.
o Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
? Any unresolved toxicity NCI CTCAE =G2 from previous anticancer therapy, except for of alopecia, vitiligo, and lab values defined in the inclusion criteria:
o =G2 neuropathy will be evaluated on a case-by-case basis.
o Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
? 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:
o Patients with vitiligo or alopecia.
o Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement.
o Any chronic skin condition that does not require systemic therapy.
o Patients without active disease in the last 5 years may be included but only after consultation with the study physician.
o 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:
o 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.
o Adequately treated non-melanoma skin cancer or lentigomaligna without evidence of disease.
o Adequately treated carcinoma in situ without evidence of

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified