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Breast CancerPhase 2NCT02725489

Pilot Study of Durvalumab and Vigil in Advanced Women's Cancers

A Phase 2 study testing Vigil and Durvalumab in people with Breast Cancer and Ovarian Cancer, run by Mary Crowley Medical Research Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

In this study, the researchers want to learn more about Vigil and durvalumab in advanced women's cancers: 1) how much of Vigil in combination with durvalumab (MEDI4736) can be given with an acceptable level of side effects, 2) the effects of Vigil and durvalumab in combination (good and bad), 3) if Vigil will cause… Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Vigil and Durvalumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteUnited States
Study dates
3 Jun 2016to 2 Dec 2020
Phase
Phase 2
Are there results?
None posted in the registry

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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Tissue Procurement Inclusion Criteria:
  • Ability to understand and the willingness to sign a written informed consent document for tissue harvest
  • 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.
  • Histologically or cytologically confirmed diagnosis of women's cancer, inclusive, but not limited to breast, ovarian, fallopian tube, primary peritoneal, uterine, cervical, endometrial, that is locally advanced or metastatic for which the projected response rate to durvalumab is 15% or less.
  • Female patients age ≥ 18 years
  • No prior Vigil immunotherapy
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  • Treatment-naïve or refractory (no response to checkpoints) / resistant (initial response but relapse) to PD-1 or PD-L1 inhibitor therapy
  • ECOG Performance Status ≤ 1
  • Estimated survival ≥ 6 months
  • Planned standard of care surgical procedure (e.g., tumor biopsy or palliative resection or thoracentesis) and expected availability of a cumulative mass of ~10-30 grams tissue ("golf-ball" size) or pleural fluid estimated volume ≥ 500mL (must be primary tap) for immunotherapy manufacture.
  • One lesion not previously irradiated nor intended for vaccine manufacture, which can be biopsied with minimal invasion and measurable at baseline as per RECIST 1.1 guidelines (performed prior to biopsy) or 2 lesions not previously irradiated nor intended for vaccine manufacture, one of which can be biopsied with minimal invasion and the other of which is measurable at baseline as per RECIST 1.1 guidelines. If the only such target lesion has previously been irradiated it must have shown unequivocal evidence of disease progression following completion of radiation therapy. Alternative methods of disease assessment, e.g. measurement of tumor markers or ascites/pleural fluid, may be considered by the Sponsor on a case-by-case basis.
  • Provision of tumor tissue sample (archived or fresh) to allow for PD-L1 expression analysis
  • Study Enrollment Inclusion Criteria:
  • Successful manufacturing of at least 4 vials of Vigil.
  • Ability to understand and the willingness to sign a written informed consent document
  • 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.
  • Estimated survival of ≥ 6 months
  • Provision of tumor tissue sample (archived or fresh) in a quantity sufficient to allow for PD-L1 expression analysis (if not already obtained during tissue procurement under this protocol), and after entry, a portion of Vigil harvested tissue
  • If female of childbearing potential, has a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a negative serum test will be required for study entry. Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, complete hysterectomy, or surgery for gynecological cancer) or postmenopausal (defined as 12 months with no menses without an alternative medical cause).
  • Adequate organ and bone marrow function as defined below:
  • Absolute neutrophil count (ANC) > 1.5 × 10^9/L (1500 per mm^3)
  • Platelets > 100 × 10^9/L (100,000 per mm^3)
  • Hemoglobin ≥ 9.0 g/dL (5.59 mmol/L)
  • Creatinine clearance (CrCL) > 50 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance:
  • Females: CrCL (mL/min) = Weight (kg) × (140 - Age) × 0.85 / 72 × serum creatinine (mg/dL)
  • Serum bilirubin ≤ 1.5 × upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of evidence of hemolysis or hepatic pathology) who will be allowed in consultation with their physician.
  • AST and ALT ≤ 2.5 × ULN in patients with no liver metastasis
  • AST or ALT ≤ 5 × ULN in patients with liver metastasis
  • TSH within institutional limits. If TSH is greater or less than institutional limits patients may participate if their T4 is within normal limits (WNL); patients may be on a stable dose of replacement thyroid medication; dose adjustments are allowed if needed.
  • Subject has recovered to CTCAE Grade 1 or better from all adverse events associated with prior therapy or surgery
  • Pre-existing motor or sensory neurologic pathology or symptoms must be recovered to CTCAE Grade > 2 or better
  • Patients with irreversible toxicity that is not reasonably expected to be exacerbated by the IPs may be included (e.g., hearing loss) after consultation with the Medical Monitor
  • Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) prior to tissue procurement and at least 21 days prior to the first dose of study drug (at least 21 days prior to the first dose of study drug for subjects who have received prior TKIs [e.g., erlotinib, gefitinib and crizotinib] and within 6 week for nitrosourea or mitomycin C). (If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period may be required.)

Who cannot join

  • Tissue Procurement Exclusion Criteria:
  • Concurrent enrollment in another clinical study, unless it is an observational (noninterventional) clinical study or the follow-up period of an interventional study.
  • Medical condition requiring any form of chronic systemic immunosuppressive therapy (steroid or other) except physiologic replacement doses of hydrocortisone or equivalent (no more than 30 mg hydrocortisone or 10 mg prednisone equivalent daily for < 30 days duration.
  • Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent.
  • Known history of other malignancy unless having undergone curative intent therapy without evidence of that disease for ≥ 5 years except cutaneous squamous cell and basal cell skin cancer, superficial bladder cancer, in situ cervical cancer or other in situ cancers are allowed if definitively resected.
  • History of brain metastases unless treated with curative intent (gamma knife or surgical resection) and without evidence of progression for ≥ 4 months.
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  • Any documented history of autoimmune disease with exception of Type 1 diabetes on stable insulin regimen, hypothyroidism on stable dose of replacement thyroid medication, vitiligo, or asthma not requiring systemic steroids (unless within the protocol allowed doses).
  • Known history of allergies or sensitivities to gentamicin, Durvalumab, or any excipient.
  • History of or current evidence of any condition (including medical, psychiatric or substance abuse disorder), therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
  • Known HIV or acute or chronic Hepatitis B or C infection.
  • History of pneumonitis or interstitial lung disease.
  • History of organ transplant that requires therapeutic immunosuppression
  • Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
  • History of Peptic Ulcer Disease or gastritis
  • History of primary immunodeficiency
  • History of leptomeningeal carcinomatosis
  • Known history of previous clinical diagnosis of tuberculosis
  • Previous allogeneic bone marrow transplant
  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
  • Previous enrollment in the present study
  • Study Enrollment Exclusion Criteria:
  • Palliative radiotherapy within 3 weeks of start of study therapy. Limited field of radiation for palliation greater than 3 weeks prior to the first dose of study treatment is allowed:
  • Provided the lung is not in the radiation field
  • Provided irradiated lesion(s) cannot be used as target lesions
  • Receipt of steroid therapy during the last 2 weeks prior to study enrollment and study treatment start.
  • Post-surgery complication that in the opinion of the treating investigator would interfere with the patient's study participation or not be in the best interest of the patient to participate
  • Receipt of live, attenuated vaccine within 30 days prior to the first dose of Vigil or Durvalumab. NOTE: Subjects, if enrolled, should not receive live vaccine during the study and 30 days after the last dose of both drugs.
  • Post-surgery complication that in the opinion of the treating investigator would interfere with the patient's study participation or make it not in the best interest of the patient to participate
  • Participation in another clinical study with an investigational product during the last 3 weeks
  • Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction
  • Female subjects who are pregnant, breast-feeding or of reproductive potential who are not employing an effective method of birth control defined in the protocol (section 7.6)
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mary Crowley Cancer Research Center

    Dallas, Texas, 75230

Other trials in United States

About this study

Official title: Pilot Study of Durvalumab (MEDI4736) in Combination With Vigil in Advanced Women's Cancers

In this study, the researchers want to learn more about Vigil and durvalumab in advanced women's cancers: 1) how much of Vigil in combination with durvalumab (MEDI4736) can be given with an acceptable level of side effects, 2) the effects of Vigil and durvalumab in combination (good and bad), 3) if Vigil will cause changes in cancer cells that may help durvalumab attack the cancer, and 4) whether or not Vigil and durvalumab will slow your cancer or stop your cancer from getting worse.

Combining Vigil with durvalumab will allow the former to induce (or increase) the infiltration of activated T cells into tumors, and in addition, to enhance PD-L1 (programmed cell death ligand 1) expression. Consequently, the response rate of historically low or un-responsive cancer will be increased with the combination of Vigil and anti PD-L1.

Read the detailed description

This is an open label pilot study to evaluate the safety, tolerability, and efficacy of the combination of Vigil autologous tumor cell immunotherapy and durvalumab PD-L1 inhibitor in patients with locally advanced or metastatic women's cancers, inclusive, but not limited to breast, ovarian, cervical, uterine, fallopian, primary peritoneal, and endometrial regardless of the number of prior therapies.

This will be a 2-part study. The first part will be a safety run-in comprised of 2 cohorts that will use a 3 + 3 design to determine the Vigil dose in Part 2. Patients in Cohort 1 will receive a low dose of Vigil (1x10^6 cells/intradermal (ID) injection) in combination with durvalumab (1500 mg (if > 30 kg) IV over 60 minutes) every 4 weeks. Patients in Cohort 2 will receive Vigil at 1x10^7 cells/ID injection and durvalumab (1500mg (if > 30 kg) IV over 60 minutes) every 4 weeks. If needed, patients in Cohort -1 will receive Vigil at 1x10^5 cells/ID injection and durvalumab (1500mg (if > 30 kg) IV over 60 minutes) every 4 weeks. The enrollment of the first two patients in each Cohort of Part 1 will be staggered by 2 weeks. In Part 2 of the study, patients meeting study eligibility criteria will receive Vigil at the dose determined in Part 1 and durvalumab (1500mg (if > 30 kg) IV over 60 minutes) every 4 weeks. As of March 13, 2018, Part 2 of the study will not be initiated due to limited enrollment. Currently only patients who have Vigil immunotherapy available from Gradalis protocol CL-PTL-119 may be considered for the study.

Radiological assessment of tumor response or alternative assessments of disease status should be performed at screening, Cycle 3 and every 2 cycle thereafter, and end of treatment (EOT) using RECIST 1.1 and investigator assessment as applicable. Tumor biopsy for correlative studies including but not limited to scoring of tumor infiltrating lymphocyte (TIL) and PD-1 / PD-L1 expression analysis should be obtained at tissue procurement and at Cycle 3, and optional biopsies thereafter if the patient has accessible tissue. Peripheral blood mononuclear cells (PBMC) for correlative studies should be obtained at pre-procurement if applicable, and prior to study regimen administration at Cycle 1, Cycle 3, Cycle 5 and EOT. Patient survival will be followed for 1 year after last dose of either Vigil or durvalumab.

Being tested
Vigil, Durvalumab
Keywords
Vigil, durvalumab, MEDI4736, PD-L1, anti PD-L1, immunotherapy, PD-L1 inhibitor, breast cancer, ovarian cancer, fallopian tube cancer, primary peritoneal cancer, uterine cancer, cervical cancer, endometrial cancer
Medical subject headings
Breast Neoplasms, Ovarian Neoplasms, Fallopian Tube Neoplasms, Uterine Neoplasms, Uterine Cervical Neoplasms, Endometrial Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VigilBiological

    Also called bi-shRNAfurin and GMCSF Autologous Tumor Cell Immunotherapy, FANG

    Vigil is made up of irradiated autologous tumor cells which have been electroporated ex vivo with the Vigil plasmid designed to suppress expression of both the TGFβ1 and TGFβ2 proteins while simultaneously expressing rhGMCSF protein.

  • DurvalumabDrug

    Also called MEDI4736

    A human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody directed against programmed cell death ligand 1 (PD-L1)

Study groups in NCT02725489
Study groupRoleWhat they receive
Part 1 Cohort 1: 1x10^6 cells VigilExperimentalThe first part will be a safety run-in comprised of 2 cohorts that will use a 3 + 3 design to determine the Vigil dose in Part 2. Cohort 1 will receive a low dose of Vigil (1x10^6 cells/intradermal (ID) injection) in combination with durvalumab (1500 mg (if > 30 kg) IV over 60 minutes) every 4 weeks.
Receives: Biological: Vigil; Drug: Durvalumab
Part 1 Cohort 2: 1x10^7 cells VigilExperimentalCohort 2 will receive Vigil at 1x10^7 cells/ID injection and durvalumab (1500mg (if > 30 kg) IV over 60 minutes) every 4 weeks.
Receives: Biological: Vigil; Drug: Durvalumab
Part 1 Cohort -1: 1x10^5 cells VigilExperimentalIf needed, Cohort -1 will be used which will receive Vigil at 1x10^5 cells/ID injection and Durvalumab (1500mg (if > 30 kg) IV over 60 minutes) every 4 weeks.
Receives: Biological: Vigil; Drug: Durvalumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of treatment-emergent AEs of Vigil + Durvalumab

    The safety evaluation will include collection of AEs, SAEs and changes from baseline in laboratory evaluations, vital signs, ECGs and physical exams. AEs will be graded according to the NCI CTCAE v4.03.

    Measured: Up to 90 days after last dose of study treatment

Secondary outcomes (3)

  1. Overall response rate (ORR)

    The ORR will be estimated in patients with measurable disease, along with its exact binomial 95% confidence interval.

    Measured: Up to 12 months after start of study treatment

  2. Disease status

    Disease status will be summarized based on tumor markers or ascites/pleural fluid in patients with non-measurable disease

    Measured: Up to 12 months after start of study treatment

  3. IFNγ-ELISPOT conversion rate (negative to positive) during on-study treatment

    Measured: 12 weeks after start of study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Apr 2016 (estimated)
  2. Study start3 Jun 2016
  3. Primary completion30 Dec 2019
  4. Study completion2 Dec 2020

Resources

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02725489
Sponsor's protocol ID
16-06
Other IDs
CL-PTL 124, ESR-15-11306
Status last verified
Jan 2021
First submitted
23 Mar 2016
Last updated
27 Jan 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Vigil and Durvalumab in people with Breast Cancer and Ovarian Cancer, run by Mary Crowley Medical Research Center at 1 site in United States.

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 33 inclusion and 32 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 27 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Number of treatment-emergent AEs of Vigil + Durvalumab (time frame: Up to 90 days after last dose of study treatment). 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 NCT02725489.

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 27 Jan 2021.

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