TLR8 Agonist VTX-2337 and Cyclophosphamide in Treating Patients With Metastatic, Persistent, Recurrent, or Progressive Solid Tumors

NCT02650635 | Terminated Phase 1 DMC

• 3 other identifiers: MC1245NCI-2015-02150P30CA015083
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trial studies the best way of TLR8 Agonist VTX-2337 and cyclophosphamide in treating patients with a solid tumor that has spread from the primary site (place where it started) to other places in the body (metastatic), progressed for a long time (persistent), come back (recurrent), or is growing, spreading, or getting worse (progressed). TLR8 Agonist VTX-2337 may stimulate the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving TLR8 Agonist VTX-2337 together with cyclophosphamide may be a better treatment for solid tumors.

Conditions

Colorectal Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma; Recurrent Breast Carcinoma; Recurrent Colorectal Carcinoma; Recurrent Melanoma of the Skin; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Renal Cell Carcinoma; Solid Neoplasm; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma; Stage IVA Colorectal Cancer; Stage IVA Pancreatic Cancer; Stage IVB Colorectal Cancer; Stage IVB Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Change in pharmacodynamics after TLR8 agonist VTX-2337 alone vs TLR8 agonist VTX-2337+cyclophosphamide

  The pharmacodynamics after TLR8 agonist VTX-2337 alone will be compared to TLR8 agonist VTX-2337+cyclophosphamide to test the hypothesis that TLR8 agonist VTX-2337+cyclophosphamide (course 2) will be significantly more immunomodulatory than TLR8 agonist VTX-2337 alone (course 1 run in dose) in regards to (1) reducing % and absolute numbers of Tregs compared to total lymphocytes; (2) reducing absolute numbers of MDSCs; (3) increasing % of total peripheral T cells activatable to produce IFNg; and (4) increasing % of total peripheral monocytes activatable to produce nitric oxide or express induci

  Up to end of course 2 (42 days)

Secondary Outcomes (5)

• Duration of response, assessed by irDOR, defined for all evaluable patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented

  Up to 36 months

• Incidence of adverse events of cyclophosphamide and TLR8 agonist VTX-2337, using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  Up to 36 months

• Overall response rate assessed by irBORR

  Up to 36 months

• Overall survival (OS)

  Time from study entry to death due to any cause, assessed up to 36 months

• PFS as measured by serial imaging studies and assessed by irRECIST

  Time from study entry to the first of either progression or death due to any cause, assessed up to 36 months

Other Outcomes (1)

• Changes in immunomodulation

  Baseline to up to day 1 of course 3 (day 63)

Study Arms (1)

Treatment (CTX, pegfilgrastim, TLR8 agonist VTX-2337)

EXPERIMENTAL

Patients receive cyclophosphamide IV over 30 minutes on day 1, pegfilgrastim SC on day 2, and TLR8 agonist VTX-2337 SC on day -6 of course 1 only and on days 9 and 16. Patients achieving CR, PR, or SD may continue therapy every 21 days for 3 additional courses. Treatment may then continue in the absence of disease progression or unacceptable toxicity.

Drug: Cyclophosphamide; Other: Laboratory Biomarker Analysis; Biological: Pegfilgrastim; Other: Pharmacological Study; Drug: TLR8 Agonist VTX-2337

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (CTX, pegfilgrastim, TLR8 agonist VTX-2337)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (CTX, pegfilgrastim, TLR8 agonist VTX-2337)

Pegfilgrastim BIOLOGICAL

Given SC

Also known as: Filgrastim SD-01, filgrastim-SD/01, HSP-130, Neulasta, Pegfilgrastim Biosimilar HSP-130, SD-01, SD-01 sustained duration G-CSF

Treatment (CTX, pegfilgrastim, TLR8 agonist VTX-2337)

Pharmacological Study OTHER

Correlative studies

Treatment (CTX, pegfilgrastim, TLR8 agonist VTX-2337)

TLR8 Agonist VTX-2337 DRUG

Given SC

Also known as: Toll-like Receptor 8 Agonist VTX-2337, VTX-2337

Treatment (CTX, pegfilgrastim, TLR8 agonist VTX-2337)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed metastatic solid tumor, including but not limited to pancreatic adenocarcinoma, breast cancer, melanoma, renal cell carcinoma (RCC), colorectal adenocarcinoma, non-small cell lung cancer, and others approved by the principal investigator
• Persistent, recurrent or progressive disease following at least one prior line of systemic therapy and there is no available therapy likely to improve survival
• Measurable disease with \>= 1 target lesion
• White blood cells (WBC) \>= 4200/mm\^3
• Absolute neutrophil count (ANC) \>= 1400/mm\^3
• Platelets (PLT) \>= 100,000/mm\^3
• Lymphocytes \>= 700/mm\^3
• Hemoglobin \>= 10 g/dL
• Total bilirubin =\< 1.5 X upper limit of normal (ULN) unless history of Gilbert's syndrome documented prior to first-line treatment of cancer and other liver function tests are within normal limits
• Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) =\< 1.2 x ULN unless on anticoagulation medication with stable dosing for at least one month; in addition, patient must be able to stop taking medication for up to a week in order to have percutaneous biopsies of tumor tissue performed
• Aspartate transaminase (AST) and alanine aminotransferase (ALT) =\< 1.5 x ULN (=\< 5 x ULN for patients with liver involvement)
• Creatinine =\< ULN or a calculated creatinine clearance of \>= 45 ml/min if creatinine is greater than the ULN
• Alkaline phosphatase =\< 3 x ULN (=\< 5 x ULN if liver or bone involvement)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Willing and able to provide informed written consent

You may not qualify if:

• Is pregnant, breastfeeding, or planning a pregnancy
• Known standard therapy for the patient's disease that is potentially curative
• Treatment with any systemic anticancer treatment or an investigational agent within 4 weeks and any radiation within 2 weeks of registration
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit subject safety or compliance with study requirements
• Active autoimmune disease, defined as any autoimmune condition currently requiring therapy (e.g., systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis)
• History of other invasive malignancy, with the exception of non-melanoma skin cancer and well-excised cervical carcinoma in situ, =\< 3 years prior to enrollment unless assessed by the principal investigator as unlikely to compromise subject safety or to interfere with the study's objectives
• Treatment with oral or parenteral corticosteroids dosed greater than 40 mg hydrocortisone daily or its equivalent (e.g., prednisone 10 mg, prednisolone 8 mg, or decadron 3 mg) =\< 2 weeks of treatment initiation; or a clinical requirement for ongoing systemic immunosuppressive therapy
• History of central nervous system (CNS) metastases unless previously treated and stable for \> 8 weeks prior to study initiation
• Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive
• Hypersensitivity to pegfilgrastim or Escherichia (E.) coli derived proteins

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Colorectal Neoplasms; Melanoma; Carcinoma, Non-Small-Cell Lung; Pancreatic Neoplasms; Carcinoma, Renal Cell

Interventions

Cyclophosphamide; pegfilgrastim; VTX-2337

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Peter Cohen

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2015
• First Posted: January 8, 2016
• Study Start: February 5, 2016
• Primary Completion: September 26, 2016
• Study Completion: June 1, 2017
• Last Updated: September 5, 2018

Record last verified: 2018-08

Locations

US (1)