Clinical trial NCT03094286: Durvalumab in HIV-1 Patients With Solid Tumors
Official title: A Phase II Exploratory Study of Durvalumab (MEDI4736) in HIV-1 Patients With Advanced Solid Tumors.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV
Cancer
Keywords: HIV
HIV with cancer patient
D006678
Lead sponsor: Spanish Lung Cancer Group
Sponsor class: OTHER
First posted: 2017-03-29
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Durvalumab will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous(IV) administration
Primary purpose: TREATMENT

Brief summary: The proposal is a phase II clinical study designed to assess the feasibility of durvalumab (MEDI4736) in HIV-1-infected individuals with solid tumors. Additionally, to obtain data that lets understand the possible benefit of this treatment in cancer patients and HIV infection, exploring if activity of durvalumab (MEDI4736) could be higher in cancer that has been produced at least in part due to the chronic immunosupression. Simultaneously, it will allow us to investigate the effect of disrupting this immunoregulatory pathway might have in reversing cancer pathways and HIV-specific T-cell function during persistent chronic HIV infection in humans.

Detailed description: PD-1/ PD-L1 coinhibitory pathway plays a significant role in the regulation of the immune response in both chronic infectious diseases and cancer.

Preclinical and animal data support the safety and promising activity of anti-PD-1 antibody in HIV-1 infection.

Demonstrated anticancer activity and safety profile of durvalumab (MEDI4736) in cancer clinical trials.

Unlikely drug interactions of durvalumab (MEDI4736) and antiretroviral treatments.

The proposal is a phase II clinical study designed to assess the feasibility of durvalumab (MEDI4736) in HIV-1-infected individuals with solid tumors. Additionally, to obtain data that lets understand the possible benefit of this treatment in cancer patients and HIV infection, exploring if activity of durvalumab (MEDI4736) could be higher in cancer that has been produced at least in part due to the chronic immunosupression. Simultaneously, it will allow us to investigate the effect of disrupting this immunoregulatory pathway might have in reversing cancer pathways and HIV-specific T-cell function during persistent chronic HIV infection in humans.

In this regard, our hypothesis is:

HIV patients with cancer have a similar outcome in terms of tolerability when treated with durvalumab (MEDI4736) monotherapy at the recommended dose than non HIV infected patients.

Eligibility criteria: Inclusion Criteria:

1. Written informed consent
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.
6. Female subjects must either be of non-reproductive potential
7. Subject is willing and able to comply with the protocol
8. Subjects with histologically or cytologically advanced/metatasic-documented lung cancer, head and neck cancer, cervical cancer, melanoma, anal cancer, pancreatic cancer, gastrio-esophageal cancer, triple negative breast cancer, bladder or renal cancer, Cholangiocarcinoma, Kaposi sarcoma, lymphomas, ovarian cancer or Merkel cell carcinoma or any other tumor type in which anti PD-L1 antibodies have desmonstrated antitumoral activity, 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.
12. Undetectable viral load in the last analysis.
13. 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\<10mb daily prednisone or equivalent.
14. Subjects must be following an antiretroviral therapy at the moment of the inclusion.

Exclusion Criteria:

1. Involvement in the planning and/or conduct of the study. Previous enrollment in the present study.
2. Participation in another clinical study within 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 within 28 days prior to the first dose of study drug.
6. Mean QT interval corrected for heart rate (QTc) ≥470 ms
7. Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab,
8. Any unresolved toxicity (CTCAE grade 2) from previous anti-cancer therapy.
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
11. Any syndrome that requires systemic corticosteroid/immunosuppressive medications
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
17. Known history of active 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, 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 reproductive potential who are not employing an effective method of birth control.
22. Symptomatic or uncontrolled brain metastases
23. Subjects with uncontrolled seizures.
24. Patients with tumoral disease in the head and neck region, such as peritracheal or periesophageal lymph node involvement,
25. Patients with neuroendocrine tumors of pulmonary origin or pulmonary metastases with evidence of active bleeding
26. Patients with digestive bleeding

Primary outcomes:
measure: Best Response During the Treatment Period
timeFrame: From the first dose until last follow up, assessed up to 24 month
Secondary outcomes:
measure: Duration of Response Global
timeFrame: From the time from first response evaluation to progression or death, assessed up to 24 months.
measure: Progression Free Survival (PFS)
timeFrame: From the date of randomization until end of follow up, assessed up to 24 months.
measure: Duration of Response- Dolutegravir/ no Dolutegravir
timeFrame: From the date of first response until progression or death, assessed up to 24 months.
measure: Duration of Response by Treatment With INSTIs or no INSTIs
timeFrame: From the date of the first response until progression or death, assessed up to 24 months
measure: OS Analysis by PD-L1
timeFrame: OS is defined as the time from the inclusion date to the death, due to any cause. A patient who does not dies, is censored up to 24 months
measure: OS Analysis by Integrase Inhibitors
timeFrame: From the time from the inclusion date to the death, due to any cause. A patient who does not dies, is censored up to 24 months
measure: OS Analysis by Dolutegravir
timeFrame: From the time from the inclusion date to the death, due to any cause. A patient who does not dies, is censored up to 24 months
measure: PFS Analysis by PD-L1
timeFrame: PFS is defined as the time from the inclusion date to the progression or death, due to any cause, up to 24 months patient who does not progresses neither dies, is censored at the last tumor evaluation where no progression is detected.
measure: PFS Analysis by Integrase Inhibitors
timeFrame: From the inclusion date to the progression or death, due to any cause, up to 24 months. patient who does not progresses neither dies, is censored at the last tumor evaluation where no progression is detected.
measure: PFS Analysis by Dolutegravir
timeFrame: From the inclusion date to the progression or death, due to any cause, assessed up to 24 months.
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: ICO-Badalona
state: Barcelona
city: Terrassa
country: Spain
facility: Consorci Sanitari de Terrassa
state: Barcelona
city: Barcelona
country: Spain
facility: H. Clínic i Provincial de Barcelona
city: Barcelona
country: Spain
facility: H. Universitario Quirón Dexeus
city: Madrid
country: Spain
facility: Hospital Puerta de Hierro
city: Madrid
country: Spain
facility: H. La Paz
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital La Fe
Study officials:
affiliation: Instituto Oncológico Dr Rosell
name: María González-Cao, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gonzalez-Cao M, Moran T, Dalmau J, Garcia-Corbacho J, Bracht JWP, Bernabe R, Juan O, de Castro J, Blanco R, Drozdowskyj A, Argilaguet J, Meyerhans A, Blanco J, Prado JG, Carrillo J, Clotet B, Massuti B, Provencio M, Molina-Vila MA, Mayo de Las Casa C, Garzon M, Cao P, Huang CY, Martinez-Picado J, Rosell R. Assessment of the Feasibility and Safety of Durvalumab for Treatment of Solid Tumors in Patients With HIV-1 Infection: The Phase 2 DURVAST Study. JAMA Oncol. 2020 Jul 1;6(7):1063-1067. doi: 10.1001/jamaoncol.2020.0465.