Talimogene Laherparepvec in Treating Patients with Locally Advanced, Metastatic, or Refractory Pancreatic Cancer That Cannot Be Removed by Surgery

Status: Active

Description

This phase I trial studies the side effects and best dose of talimogene laherparepvec in treating patients with pancreatic cancer that cannot be removed by surgery and has spread from where it started to nearby tissue, lymph nodes (locally advanced), or to other places in the body (metastatic), or that does not respond to treatment (refractory). Talimogene laherparepvec may help infect and kill tumor cells and activate the body’s own immune cells to destroy the tumor cells throughout the body.

Eligibility Criteria

Inclusion Criteria

  • Patient must have pathologically confirmed, locally advanced or metastatic pancreatic ductal adenocarcinoma (PDA) deemed surgically unresectable by a surgeon with expertise in pancreatic cancer
  • Disease must be refractory to or intolerant of at least first-line chemotherapy which contains 5-fluorouracil or gemcitabine
  • The primary lesion must be accessible for endoscopic biopsy and injection as evaluated by a gastroenterologist at New York-Presbyterian (NYP)-Columbia; further, the patient must be deemed able to tolerate repeated endoscopy procedures by an anesthesiologist and/or gastroenterologist at NYP-Columbia
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Radiologically measurable injectable disease in the pancreas or surgical bed from prior >= 1 cm, as defined by RECIST v1.1
  • Ability to understand and the willingness to sign a written informed consent document
  • Females of child-bearing potential (defined as a sexually mature woman who [1] has not undergone hysterectomy [the surgical removal of the uterus] or bilateral oophorectomy [the surgical removal of both ovaries] or [2] has not been naturally postmenopausal for at least 24 consecutive months [i.e., has had menses at any time during the preceding 24 consecutive months]) must: * Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis), or agree to use, and be able to comply with, effective contraception (=< 1% failure rate annually) without interruption, 28 days prior to starting therapy (including dose interruptions), and while on study medication or for a period of 3 months following treatment completion; (periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception) * Have a negative urine or serum pregnancy test within 72 hours prior to enrollment; if urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required; this applies even if the subject practices true abstinence* from heterosexual contact
  • Male subjects must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 30 days following treatment discontinuation, even if he has undergone a successful vasectomy
  • Hemoglobin >= 8.0 g/dl
  • Platelets >= 75,000/mcL
  • Absolute neutrophil count (ANC) >= 1500/mm^3 (1.5 x 10^9/L)
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) OR direct bilirubin =< ULN with total bilirubin > 1.5 x ULN
  • Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) =< 1.5 x ULN
  • International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN; unless the patient is on therapeutic anticoagulation in which case the INR and aPTT must be within the therapeutic range of intended use of anti-coagulants
  • Serum creatinine =< 1.5 x ULN OR
  • 24 hour creatinine clearance >= 60 mL/min/1.73 m^2 by Cockcroft-Gault
  • Lipase =< 3 x ULN

Exclusion Criteria

  • Cystic pancreatic cancer; microcystic disease may be eligible
  • Patients with PDA metastases deemed likely to limit the patient’s ability to participate in the study for the complete duration (ie. > 3 months), including but not limited to: * Presence of central nervous system (CNS) metastasis including brain metastasis or compromise resulting from extrinsic disease in the bone or dura * Presence of more than 5 liver metastases or one liver metastasis measuring more than 3 cm * Oxygen requirement attributable to pleural effusion or other malignant process * Symptomatic ascites
  • History of other malignancy within the past 3 years with the following exceptions: * Malignancy treated with curative intent and with no known active disease present and has not received chemotherapy for > 3 years before randomization and felt to be at low risk for recurrence by the treating physician * Adequately treated non-melanoma skin cancer without evidence of disease at the time of randomization * Adequately treated cervical carcinoma in situ without evidence of disease at the time of randomization * Adequately treated breast ductal carcinoma in situ without evidence of disease at the time of randomization * Prostatic intraepithelial neoplasia without evidence of prostate cancer at the time of randomization * Adequately treated superficial or in situ carcinoma of the bladder without evidence of disease at the time of randomization
  • Pancreatitis that is active or within the preceding 3 months which in the judgment of the endoscopist would make tumor injection likely to trigger severe recurrent pancreatitis
  • Prior chemotherapy or radiotherapy within 14 days prior to first dose of therapy provided subject has received no growth factor support of any kind within 28 days prior to first dose of therapy, otherwise prior chemotherapy within 28 days prior to first dose of therapy
  • Radiation to the abdominal area within 28 days of first dose of therapy or prior radiotherapy in which the field does not overlap the injection sites or non-immunosuppressive targeted therapy within 14 days prior to enrollment or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or better from adverse event due to cancer therapy administered more than 14 days prior to enrollment
  • The patient has not recovered to CTCAE grade 1 or better from adverse event at time of enrollment due to cancer therapy administered more than 28 days prior to enrollment
  • Prior biological cancer therapy, targeted therapy, or major surgery within 28 days prior to first dose of therapy or major surgery within 28 days prior to enrollment or has not recovered to CTCAE grade 1 or better from adverse event due to cancer therapy administered more than 28 days prior to enrollment; adjuvant hormonal therapy is allowed
  • Unresolved grade 2 or greater toxicity from most recent treatment, including chemotherapy, hormonal therapy, or radiotherapy, at the time of study enrollment
  • The following ongoing treatments are permitted: * Hormone-replacement therapy or oral contraceptives * Hormone therapy for primary prevention of breast cancer
  • Patients may not receive Coumadin while on study; patients may receive low molecular weight heparin or novel oral anticoagulants (eg. dabigatran, apixaban, rivaroxaban) provided that the dose is held 1-2 days before injections are given and biopsies are performed per the protocol; anti-platelet agents and herbal substances are allowed at the discretion of the treating endoscopist
  • Active herpetic skin lesions or prior complications of herpetic infection (e.g., herpetic keratitis or encephalitis) or requires intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (e.g., acyclovir), other than intermittent topical use
  • Previous treatment with talimogene laherparepvec or any other oncolytic virus
  • Prior therapy with tumor vaccine
  • Received live vaccine within 28 days of tumor enrollment
  • Currently receiving treatment with another investigational device or drug study, or < 28 days since ending treatment with another investigational device or drug study(s); other investigational procedures while participating in this study are excluded
  • Known to have acute or chronic active hepatitis B infection, hepatitis C infection, or known to have human immunodeficiency virus (HIV) infection
  • Subject has known sensitivity to talimogene laherparepvec or any of its components to be administered during dosing
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection including tuberculosis (TB) and C. difficile, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; this includes known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
  • Severe infections within 4 weeks prior to cycle 1, day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
  • Major surgical procedure within 28 days prior to cycle 1, day 1 or anticipation of need for a major surgical procedure during the course of the study
  • Female subject of childbearing potential who is unwilling to use acceptable method(s) of effective contraception during study treatment and through 3 months after the last dose of talimogene laherparepvec; (note: women not of childbearing potential are defined as: any female who is post-menopausal [age >= 55 years with cessation of menses for 12 or more months or less than 55 years but not spontaneous menses for at least 2 years or less than 55 years and spontaneous menses within the past 1 year, but currently amenorrheic (eg, spontaneous or secondary to hysterectomy), and with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating hormone levels > 40 IU/L) or postmenopausal estradiol levels (< 5 ng/dL) or according to the definition of "postmenopausal range" for the laboratory involved] or who have had a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy)
  • Sexually active subjects and their partners unwilling to use male or female latex condom to avoid potential viral transmission during sexual contact while on treatment and within 30 days after treatment with talimogene laherparepvec
  • Nursing patients are not allowed on the study and women must commit to no lactation during the course of the study
  • Subject who is unwilling to minimize exposure with his/her blood or other body fluids to individuals who are at higher risks for herpes simplex virus (HSV)-1 induced complications such as immunosuppressed individuals, individuals known to have HIV infection, pregnant women, or children under the age of 1 year, during talimogene laherparepvec treatment and through 30 days after the last dose of talimogene laherparepvec
  • IMMUNOTHERAPY-RELATED EXCLUSION CRITERIA
  • History or evidence of active autoimmune disease that requires systemic treatment (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment for patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation * The use of inhaled or oral corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
  • Received live vaccine within 28 days prior to enrollment
  • Evidence of clinically significant immunosuppression such as the following: * Primary immunodeficiency state such as severe combined immunodeficiency disease * HIV positive * Receiving systemic immunosuppressive therapy (> 2 weeks) including oral steroid doses > 10 mg/day of prednisone or equivalent within 2 months prior to enrollment * Concurrent opportunistic infection

Locations & Contacts

New York

New York
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: Active
Contact: Yvonne Saenger
Phone: 212-305-0455
Email: yms4@columbia.edu

Trial Objectives and Outline

PRIMARY OBJECTIVE:

I. To determine the rate of dose limiting toxicity at tested doses of talimogene laherparepvec administered endoscopically to pancreatic tumors, and to identify a maximum tolerated dose (MTD).

SECONDARY EXPLORATORY OBJECTIVES

I. To determine the activity of talimogene laherparepvec in pancreatic cancer, as measured by change in size of the injected lesion(s), overall response rate by immune related response criteria and Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1, and progression free survival (PFS) and overall survival (OS) at 6, 12, and 24 months.

II. To explore the immune effects of talimogene laherparepvec and predictors of response as determined by immunohistochemistry (IHC), flow cytometry, and genomic analysis of tumor and immune cells.

OUTLINE: This is a dose-escalation study.

Patients receive talimogene laherparepvec endoscopically at weeks 1, 4, 7, and 10 in absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year, and then annually for 5 years.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center

Principal Investigator
Yvonne Saenger

Trial IDs

Primary ID AAAQ9966
Secondary IDs NCI-2017-01528
Clinicaltrials.gov ID NCT03086642