A Phase 1/2 Study of Motolimod (VTX-2337) and MEDI4736 in Subjects With Recurrent, Platinum-Resistant Ovarian Cancer for Whom Pegylated Liposomal Doxorubicin (PLD) is Indicated
|Treatments||durvalumab, pegylated liposomal doxorubicin|
|Phase||phase 1/phase 2|
|Sponsor||Ludwig Institute for Cancer Research|
|Start date||November 2015|
|End date||June 2018|
|Trial size||53 participants|
|Trial identifier||NCT02431559, LUD2014-001|
This is an open-label, non‐randomized, multicenter Phase 1/2 study of MEDI4736 in subjects with recurrent, platinum-resistant ovarian cancer, scheduled to receive Pegylated Liposomal Doxorubicin (PLD). Subjects will be treated during each 28-day cycle according to the treatment schedule.
Recruiting in the following locations…
|United States||New York, Ohio, and Rhode Island|
|Overall contact||Lisa Shohara|
|Phoenix, AZ||Research Facitlity||not yet recruiting|
|New York, NY||Research Facility||recruiting|
|Hilliard, OH||Research Facility||recruiting|
|Providence, RI||Research Facility||recruiting|
|Lausanne, Switzerland||Research Facility||recruiting|
|Endpoint classification||safety/efficacy study|
|Intervention model||single group assignment|
Maximum Tolerated Dose (MTD) - Phase 1
time frame: 6-12 months
Assessment of Clinical Efficacy - Phase 2 (Progression Free Survival (PFS) rate at 6 months)
time frame: 6 Months
Assessment of Clinical Efficacy - Phase 1 (Progression Free Survival (PFS) rate at 6 months)
time frame: 6 months
Assessment of Clinical Efficacy - Phase 1 & 2 (progression¬‐free survival rate at 12 months)
time frame: 12 months
Female participants at least 18 years old.
- Subjects must have recurrent or persistent platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with measureable disease (as defined by RECIST 1.1.) after first or second line platinum-based chemotherapy, for which treatment with PLD is indicated. Platinum-based therapy is defined as treatment with carboplatin, cisplatin or another organoplatinum compound. Platinum-resistant is defined as having a platinum-free interval (PFI) of < 12 months after first- or second-line platinum-based chemotherapy, or having disease progression while receiving second-line platinum-based chemotherapy. Subjects are allowed to have received, but are not required to have received:
- one additional cytotoxic regimen and/or PARP inhibitor for management of recurrent or persistent disease.
- biologic therapy (e.g., bevacizumab) as part of their primary treatment regimen or part of their treatment for management of recurrent or persistent disease.
- Histologic documentation of the original primary tumor.
- Documented radiographic disease progression < 12 months after the last dose of first- or second-line platinum-based chemotherapy.
- Subjects in Phase 2 must have disease amenable to biopsy and must be willing to undergo pre- and post-treatment tumor biopsies. Optional for Phase 1. Note: archival tissue will be requested for all subjects preferably from primary tumor site prior to cancer treatment; however, archival tissue is not a requirement for study entry.
- ECOG performance status of 0 or 1.
- Laboratory parameters for vital functions should be in the normal range. Laboratory abnormalities that are not clinically significant are generally permitted, except for the following laboratory parameters, which must be within the ranges specified, regardless of clinical significance:
- Hemoglobin: ≥ 9 g/dL
- Neutrophil count: ≥ 1.5 x 109/L
- Platelet count: ≥ 100,000/mm3
- Serum creatinine, ≤ 1.5x Institutional Upper Limit of Normal (ULN), or Creatinine Clearance ≥ 50 mL/min (by Cockcroft-Gault formula)
- Serum bilirubin: ≤ 1.2 mg/dL
- AST/ALT: ≤ 2.5 x ULN
- Alkaline phosphatase: ≤ 2.5 x ULN
- Age ≥18 years.
- Able and willing to give valid written informed consent.
- Body weight > 30 kg
- Prior exposure to doxorubicin, PLD or any other anthracycline, motolimod and other TLR agonists, MEDI4736 or checkpoint inhibitors, such as anti-CTLA4 and anti-PD1/anti-PD-L1 antibodies.
- Subjects with platinum-refractory disease, defined as disease progression while receiving first line platinum-based therapy.
- Clinically significant persistent immune-related adverse events following prior therapy.
- Subjects with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or, within six months prior to Day 1 of this study, history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage.
- Subjects with clinically significant cardiovascular disease. This includes:
- Resisted hypertension
- Myocardial infarction or unstable angina within 6 months prior to Day 1 of the study.
- History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic medications, except for atrial fibrillation that is well controlled with anti-arrhythmic medication.
- Baseline ejection fraction ≤ 50% as assessed by echocardiogram or MUGA.
- New York Heart Association (NYHA) Class II or higher congestive heart failure.
- Grade 2 or higher peripheral ischemia, except for brief (< 24 hrs) episodes of ischemia managed non-surgically and without permanent deficit.
- History of pneumonitis or interstitial lung disease.
- Active, suspected or prior documented autoimmune disease (including inflammatory bowel disease, celiac disease, Wegner's granulomatosis, active Hashimoto's thyroiditis, rheumatoid arthritis, lupus, scleroderma and its variants, multiple sclerosis, myasthenia gravis). Vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted.
- Other malignancy within 2 years prior to Day 1 of the study, except for those treated with surgical intervention only.
- Subjects with clinical symptoms or signs of gastrointestinal obstruction and/or who require drainage gastrostomy tube and/or parenteral hydration or nutrition.
- Known immunodeficiency or HIV, Hepatitis B or Hepatitis C positivity.
- History of severe allergic reactions to any unknown allergens or components of the study drugs.
- Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders).
- Prior treatment in any other interventional clinical trial within 4 weeks prior to Day 1 of the study.
- Mental impairment that may compromise compliance with the requirements of the study.
- Lack of availability for immunological and clinical follow-up assessment.
- Women who are breastfeeding or pregnant as evidenced by positive serum pregnancy test
- Subjects unwilling to use acceptable methods of contraception. -Female subjects should refrain from breastfeeding throughout this period.
- Any condition that, in the clinical judgment of the treating physician, is likely to prevent the subject from complying with any aspect of the protocol or that may put the subject at unacceptable risk.
- Subjects must not donate blood while on study and for at least 90 days following the last MEDI4736 treatment.
- History of allogeneic organ transplant
|Official title||A Phase 1/2 Study of Chemo-immunotherapy With Toll-like Receptor 8 Agonist Motolimod (VTX-2337) and Anti-PD-L1 Antibody MEDI4736 in Subjects With Recurrent, Platinum-Resistant Ovarian Cancer for Whom Pegylated Liposomal Doxorubicin (PLD) is Indicated|
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