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Durvalumab in Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03094286
Recruitment Status : Active, not recruiting
First Posted : March 29, 2017
Last Update Posted : February 2, 2021
Sponsor:
Information provided by (Responsible Party):
Spanish Lung Cancer Group

Tracking Information
First Submitted Date  ICMJE March 10, 2017
First Posted Date  ICMJE March 29, 2017
Last Update Posted Date February 2, 2021
Actual Study Start Date  ICMJE April 24, 2017
Actual Primary Completion Date April 24, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 23, 2017)
Number of HIV patient that receive durvalumab at least during 4 months [ Time Frame: From the first dose until progression disease (at 1 year approximately) ]
To explore the feasibility of durvalumab (MEDI4736) monotherapy at the recommended dose of 1500mg in solid tumors in HIV-1-infected patients
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 23, 2017)
  • To assess Overall Response Rate (ORR) (RECIST 1.1 and irRECIST) [ Time Frame: From the first dose until the first response evaluation (8 weeks from the first dose) ]
    ORR according to RECIST criteria
  • To evaluate the Progression Free Survival (PFS) rate [ Time Frame: From the first dose until the first response evaluation (8 weeks from the first dose) ]
    To evaluate progression free survival rate of all the patients included
  • To evaluate the Overall Survival (OS) rate [ Time Frame: At month 12th from the first dose of Durvalumab ]
    To evaluate overall survival rate of all the patients included
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Durvalumab in Solid Tumors
Official Title  ICMJE A PHASE II EXPLORATORY STUDY OF DURVALUMAB (MEDI4736) IN HIV-1 PATIENTS WITH ADVANCED SOLID TUMORS
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
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
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • HIV
  • Cancer
Intervention  ICMJE Drug: Durvalumab
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
Other Name: MEDI4736
Study Arms  ICMJE Experimental: Arm 1
Durvalumab (MEDI4736) monotherapy at the recommended dose of 1500mg every 4 weeks in solid tumors in HIV-1-infected patients
Intervention: Drug: Durvalumab
Publications * Gonzalez-Cao M, Morán 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 23, 2017)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 24, 2022
Actual Primary Completion Date April 24, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03094286
Other Study ID Numbers  ICMJE GECP 16/04_DURVAST
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Spanish Lung Cancer Group
Study Sponsor  ICMJE Spanish Lung Cancer Group
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: María González-Cao, MD Instituto Oncológico Dr Rosell
PRS Account Spanish Lung Cancer Group
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP