Treatment of patients with HIV-1 and advanced solid tumors with Durvalumab
- Conditions
- advanced solid tumors in HIV-1 infected patientsTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-004524-38-ES
- Lead Sponsor
- Spanish Lung Cancer Group (Grupo Español de Cáncer de Pulmón)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 20
1. Written informed consent obtained from the subject prior to performing any protocolrelated
procedures, including screening evaluations.
2. Age > 18 years at time of study entry.
3. Eastern Cooperative Oncology Group (ECOG) 0-2
4. Life expectancy of > 16 weeks
5. Adequate normal organ and marrow function as defined below:
- Haemoglobin = 9.0 g/dL
- Absolute neutrophil count (ANC) = 1.5 x 109/L (> 1500 per mm3)
- Platelet count = 100 x 109/L (>100,000 per mm3)
- Serum bilirubin = 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of haemolysis 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 unless liver metastases are present, in which case it must be = 5x ULN
- Serum 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.
6. Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: =60 years old and no menses for ³1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
7. Subject 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.
8. Subjects with histologically or cytologically-documented lung cancer, head and neck cancer, cervical cancer, melanoma, anal cancer, pancreatic cancer, gastric cancer, triple negative breast cancer, bladder or renal cancer, refractory to standard treatment, intolerant of standard treatment, or for which no standard therapy exists or who refuse the standard treatment.
9. Subjects may be included irrespectively of number of previous lines of treatment for advanced disease.
10. Prior palliative radiotherapy must have been completed at least 2 weeks prior to start the study treatment (subjects may receive localized palliative radiotherapy while receiving study drug).
11. Documented HIV-1 infection with a CD4 count over 350 cells/mm3.
12. Subjects with brain metastases are eligible if they are asymptomatic, are treated or are neurological stable for at least 2 weeks without the use of steroids or on stable or decreasing dose of < 10 mg daily prednisone or equivalent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20
1. Involvement in the planning and/or conduct of the study. Previous enrollment in the present study.
2. Participation in another clinical study with an investigational product during the last 4 weeks.
3. Other untreated coexisting HIV related malignancies.
4. Any previous treatment with a PD1, PD-L1 or PD-L2 inhibitor, including durvalumab.
5. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) 28 days prior to the first dose of study drug.
6. Mean QT interval corrected for heart rate (QTc) =470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia’s Correction.
7. 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.
8. Any unresolved toxicity (CTCAE grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy).
9. Any prior Grade =3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1.
10. Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave’s disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
11. Any syndrome that requires systemic corticosteroid/immunosuppressive medications EXCEPT for syndromes which would not be expected to recur in the absence of an external trigger (vitiligo, autoimmune thyroiditis, or type 1 diabetes mellitus are permitted to enroll).
12. Active or prior documented inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis).
13. History of primary immunodeficiency.
14. History of allogeneic organ transplant.
15. History of hypersensitivity to durvalumab or any excipient.
16. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B or C, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
17. Known history ofactive tuberculosis.
18. Any serious or uncontrolled medical disorder or active infection non HIV, that would impair the ability of the subject to receive the treatment of protocol therapy under treating physician criteria.
19. Subjects with previous malignances (except non melanoma skin cancer, and cancer in situ of: bladder, gastric, colon, cervical/dysplasia, melanoma, breast) are excluded unless a complete remission was achieved at least 5 years prior to study entry and no additional therapy is required or anticipated to be required during the study period.
20. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab.
21. Female subjects who are pregnant, breast-feeding, male, or female patients of reproducti
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Secondary Objective: To assess ORR (objective response rate) (RECIST 1.1 and irRECIST) and duration of response, to evaluate the PFS (Progressive free survival) rate at 6 months, to evaluate the OS (overall survival) rate at 12 months.;Primary end point(s): To explore the feasibility of durvalumab (MEDI4736) monotherapy at the recommended dose of 1500mg every 4 weeks in solid tumors in HIV-1-infected patients.;Main Objective: To explore the feasibility of durvalumab (MEDI4736) monotherapy at the recommended dose of 1500mg every 4 weeks in solid tumors in HIV-1-infected patients.;Timepoint(s) of evaluation of this end point: At the end of the study
- Secondary Outcome Measures
Name Time Method Secondary end point(s): To assess ORR (objective response rate) (RECIST 1.1 and irRECIST) and duration of response, to evaluate the PFS (Progressive free survival) rate at 6 months, to evaluate the OS (overall survival) rate at 12 months.;Timepoint(s) of evaluation of this end point: At the end of the study