HIVPhase 2NCT03094286
Durvalumab in HIV-1 Patients With Solid Tumors
A Phase 2 study testing Durvalumab in people with HIV and Cancer, run by Spanish Lung Cancer Group at 8 sites in Spain.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- Durvalumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 8 sitesSpain
- Study dates
- 24 Apr 2017to 22 Mar 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 14Show fewer
- 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.
- Subjects must be following an antiretroviral therapy at the moment of the inclusion.
Who cannot join
- 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
Show all 26Show fewer
- 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.
- Uncontrolled intercurrent illness
- Known history of active tuberculosis.
- 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.
- 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.
- Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab.
- Female subjects who are pregnant, breast-feeding, male, or female patients of reproductive potential who are not employing an effective method of birth control.
- Symptomatic or uncontrolled brain metastases
- Subjects with uncontrolled seizures.
- Patients with tumoral disease in the head and neck region, such as peritracheal or periesophageal lymph node involvement,
- Patients with neuroendocrine tumors of pulmonary origin or pulmonary metastases with evidence of active bleeding
- Patients with digestive bleeding
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Spain8 sites
ICO-Badalona
Badalona, Barcelona, 08916
H. Clínic i Provincial de Barcelona
Barcelona, 08036
H. Universitario Quirón Dexeus
Barcelona, 08036
Hospital Puerta de Hierro
Madrid, 28222
H. La Paz
Madrid
Hospital Virgen del Rocío
Seville, 41013
Consorci Sanitari de Terrassa
Terrassa, Barcelona, 08220
Hospital La Fe
Valencia
About this study
Official title: A Phase II Exploratory Study of Durvalumab (MEDI4736) in HIV-1 Patients With Advanced Solid Tumors.
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.
Read the 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.
- Being tested
- Durvalumab
- Keywords
- HIV, HIV with cancer patient, D006678
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
Also called MEDI4736
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
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Durvalumab (MEDI4736) monotherapy at the recommended dose of 1500mg every 4 weeks in solid tumors in HIV-1-infected patients Receives: Drug: Durvalumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: From the first dose until last follow up, assessed up to 24 month
Secondary outcomes (10)
Duration of Response Global
Only patients with best response Stable disease, Partial Response or Complete response during the treatment period are included in the response analysis.
Duration of response is the time from response (R) to progression/death (P/D).
Measured: From the time from first response evaluation to progression or death, assessed up to 24 months.
Progression Free Survival (PFS)
Defined as the length of time from the date of diagnose to the date of the first documented progression of disease. "Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions".A patient who does not progresses neither dies, is censored at the last tumor evaluation where no progression is detected.
Measured: From the date of randomization until end of follow up, assessed up to 24 months.
Duration of Response- Dolutegravir/ no Dolutegravir
Only patients with best response Stable disease, Partial Response or Complete response during the treatment period are included in the response analysis.
Duration of response is the time from response (R) to progression/death (P/D).
Measured: 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
Only patients with best response Stable disease, Partial Response or Complete response during the treatment period are included in the response analysis.
Duration of response is the time from response to progression/death.
Measured: From the date of the first response until progression or death, assessed up to 24 months
OS Analysis by PD-L1
Kaplan Meier method will be used to estimate the survival function. OS will be mesure at 24 months.
Measured: 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
OS Analysis by Integrase Inhibitors
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 at the last contact date up to 24 months.
Measured: 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
OS Analysis by Dolutegravir
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
Measured: 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
PFS Analysis by PD-L1
Progression Free Survival defined as the length of time from the date of diagnosis to the date of the first documented progression of disease
Measured: 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.
PFS Analysis by Integrase Inhibitors
Defined as the length of time from the date of diagnosis to the date of the first documented progression of disease
Measured: 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.
PFS Analysis by Dolutegravir
PFS is defined as the time from the inclusion date to the progression or death, due to any cause, date.
Measured: From the inclusion date to the progression or death, due to any cause, assessed up to 24 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2017
- Study start24 Apr 2017
- Primary completion24 Apr 2019
- Study completion22 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Spanish Lung Cancer Group
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- María González-Cao, MD, Principal investigator, Instituto Oncológico Dr Rosell
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03094286
- Sponsor's protocol ID
- GECP 16/04_DURVAST
- Status last verified
- Jan 2024
- First submitted
- 10 Mar 2017
- Last updated
- 24 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 32271353
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Exploratory Study of Durvalumab (MEDI4736) in HIV-1 Patients With Advanced Solid Tumors.
- ClinicalTrials.gov ID
- NCT03094286
- Acronym / sponsor ID
- GECP 16/04_DURVAST
- Keywords
- HIV, HIV with cancer patient, D006678
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Spanish Lung Cancer GroupUniversity, hospital or other
- Study start
- 24 Apr 2017 (actual)
- Primary completion
- 24 Apr 2019 (actual)
- Study completion
- 22 Mar 2022 (actual)
- First posted
- 29 Mar 2017 (actual)
- Results
- Posted 24 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: DurvalumabDurvalumab (MEDI4736) monotherapy at the recommended dose of 1500mg every 4 weeks in solid tumors in HIV-1-infected patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (26 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DurvalumabAlso: MEDI4736Durvalumab 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 | Drug | Arm 1 |
Primary outcome
Best Response During the Treatment Period
Time frame: From the first dose until last follow up, assessed up to 24 month
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).
10 secondary outcomes
Duration of Response Global
Time frame: From the time from first response evaluation to progression or death, assessed up to 24 months.
Progression Free Survival (PFS)
Time frame: From the date of randomization until end of follow up, assessed up to 24 months.
Duration of Response- Dolutegravir/ no Dolutegravir
Time frame: 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
Time frame: From the date of the first response until progression or death, assessed up to 24 months
OS Analysis by PD-L1
Time frame: 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
OS Analysis by Integrase Inhibitors
Time frame: 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
OS Analysis by Dolutegravir
Time frame: 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
PFS Analysis by PD-L1
Time frame: 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.
PFS Analysis by Integrase Inhibitors
Time frame: 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.
PFS Analysis by Dolutegravir
Time frame: From the inclusion date to the progression or death, due to any cause, assessed up to 24 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32271353Gonzalez-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.
- Web page of the sponsor where users can find more information about Fundación GECP studiesLink provided by the sponsor.
- Publication of the results of DURVAST study in this article on JAMA Oncology in 2020Link provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for HIV
Not yet recruitingPhase 1
huCART19-IL18-CD428z Cells for the Treatment of Patients With HIV With CD19+ Cancers
Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia
Enrolling by invitation
Evaluating the Efficacy of Annual CHTC Retesting Among Male Couples at High Risk of HIV Infection
HIV Infections
RecruitingPhase 1/2
A Study of Daily Rifapentine Combined With Isoniazid (1HP) for Tuberculosis Prevention in Children Less Than 13 Years of Age With and Without HIV
Tuberculosis
Enrolling by invitation
Intervention to Reduce HIV Related Stigma Among Pregnant and Postpartum Women
HIV, HIV - Human Immunodeficiency Virus
Not yet recruitingPhase 4
Study of BIC/LEN FDC Versus Stable Baseline Regimens in Virologically Suppressed People With HIV
HIV-1 Infection
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
María González-Cao, MD principal investigator
Instituto Oncológico Dr Rosell
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Durvalumab in people with HIV and Cancer, run by Spanish Lung Cancer Group at 8 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best Response During the Treatment Period (time frame: From the first dose until last follow up, assessed up to 24 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03094286, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2024.