Durvalumab in HIV-1 Patients With Solid Tumors

NCT03094286 | Completed Phase 2 Results DMC

• 1 other identifier: GECP 16/04_DURVAST
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 8

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.

Conditions

HIV; Cancer

Keywords

HIV; HIV with cancer patient; D006678

Outcome Measures

Primary Outcomes (1)

• Best Response During the Treatment Period

  To explore the feasibility of durvalumab (MEDI4736) monotherapy at the recommended dose of 1500mg in solid tumors in HIV-1-infected patients The best overall response is a result of a combination of tumor responses in target and nontarget lesions according to Response Evaluation Criteria in Solid Tumors (RECIST).

  From the first dose until last follow up, assessed up to 24 month

Secondary Outcomes (10)

• Duration of Response Global

  From the time from first response evaluation to progression or death, assessed up to 24 months.

• Progression Free Survival (PFS)

  From the date of randomization until end of follow up, assessed up to 24 months.

• Duration of Response- Dolutegravir/ no Dolutegravir

  From the date of first response until progression or death, assessed up to 24 months.

• Duration of Response by Treatment With INSTIs or no INSTIs

  From the date of the first response until progression or death, assessed up to 24 months

• OS Analysis by PD-L1

  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

Study Arms (1)

Arm 1

EXPERIMENTAL

Durvalumab (MEDI4736) monotherapy at the recommended dose of 1500mg every 4 weeks in solid tumors in HIV-1-infected patients

Drug: Durvalumab

Interventions

Durvalumab DRUG

Durvalumab monotherapy of 1500mg every 4 weeks in solid tumors in HIV-1-infected patients until progression significant clinical deterioration, unacceptable toxicity, any criterion for withdrawal from the trial or trial drug is fulfilled

Also known as: MEDI4736

Arm 1

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
• Age \> 18 years at time of study entry.
• Eastern Cooperative Oncology Group (ECOG) 0-2
• Life expectancy of \> 16 weeks
• Adequate normal organ and marrow function.
• Female subjects must either be of non-reproductive potential
• Subject is willing and able to comply with the protocol
• 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.
• Subjects may be included irrespectively of number of previous lines of treatment for advanced disease.
• 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).
• Documented HIV-1 infection.
• Undetectable viral load in the last analysis.
• 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.

You may not qualify if:

• Involvement in the planning and/or conduct of the study. Previous enrollment in the present study.
• Participation in another clinical study within last 4 weeks.
• Other untreated coexisting HIV related malignancies.
• Any previous treatment with a PD1, PD-L1 or PD-L2 inhibitor, including durvalumab.
• Receipt of the last dose of anti-cancer therapy within 28 days prior to the first dose of study drug.
• Mean QT interval corrected for heart rate (QTc) ≥470 ms
• Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab,
• Any unresolved toxicity (CTCAE grade 2) from previous anti-cancer therapy.
• Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \>Grade 1.
• Active or prior documented autoimmune disease within the past 2 years
• Any syndrome that requires systemic corticosteroid/immunosuppressive medications
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
• History of primary immunodeficiency.
• History of allogeneic organ transplant.
• History of hypersensitivity to durvalumab or any excipient.

Sponsors & Collaborators

• Spanish Lung Cancer Group: lead

Study Sites (8)

ICO-Badalona

Badalona, Barcelona, 08916, Spain

Location

Consorci Sanitari de Terrassa

Terrassa, Barcelona, 08220, Spain

Location

H. Clínic i Provincial de Barcelona

Barcelona, 08036, Spain

Location

H. Universitario Quirón Dexeus

Barcelona, 08036, Spain

Location

Hospital Puerta de Hierro

Madrid, 28222, Spain

Location

H. La Paz

Madrid, Spain

Location

Hospital Virgen del Rocío

Seville, 41013, Spain

Location

Hospital La Fe

Valencia, Spain

Location

Related Publications (1)

• 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.

  PMID: 32271353 DERIVED

Related Links

• Web page of the sponsor where users can find more information about Fundación GECP studies
• Publication of the results of DURVAST study in this article on JAMA Oncology in 2020

MeSH Terms

Conditions

Neoplasms

Interventions

durvalumab

Results Point of Contact

• Title: Eva Pereira
• Organization: Fundación GECP

gecp@gecp.org

+34 934302006

Study Officials

• María González-Cao, MD

  Instituto Oncológico Dr Rosell

  PRINCIPAL INVESTIGATOR

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: Durvalumab will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous(IV) administration

Study Record Dates

• First Submitted: March 10, 2017
• First Posted: March 29, 2017
• Study Start: April 24, 2017
• Primary Completion: April 24, 2019
• Study Completion: March 22, 2022
• Last Updated: June 24, 2024
• Results First Posted: June 24, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (8)