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

Completed · Phase 2

Conditions studied: Breast Cancer, Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Carcinoma, Uterine Cancer, Cervical Cancer, Endometrial Cancer

In brief

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.

Key facts

Study ID

NCT02725489

Run by

Mary Crowley Medical Research Center

People needed

13

Starts

2016-06-03

Expected to finish

2020-12-02

Last updated by the study team

2021-01-27

Who can join

Age: 18 and older. Sex: female. Healthy volunteers: not accepted.

You may qualify if…

• 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
• 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)

You may not qualify if…

• 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.
• 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.

Where it is running

• Mary Crowley Cancer Research Center — Dallas, Texas, United States

Full record on ClinicalTrials.gov

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