Immunotherapy Study of Evofosfamide in Combination With Ipilimumab

NCT03098160 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: TH-CR-417
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

An immunotherapy study combining ipilimumab and evofosfamide for the treatment of patients with confirmed metastatic or locally advanced prostate cancer, metastatic pancreatic cancer, melanoma or human papillomavirus (HPV) negative squamous cell carcinoma of head and neck that have failed to respond to standard therapy, progressed despite standard therapy, for which standard therapy does not offer the potential for increased survival.

Conditions

Pancreatic Cancer; Melanoma; Squamous Cell Carcinoma of the Head and Neck; Prostate Cancer

Keywords

Immunotherapy; Hypoxia; Evofosfamide; Ipilimumab; TH-302

Outcome Measures

Primary Outcomes (1)

• Recommended phase 2 dose (RP2D) determined after maximally tolerated dose is set and four dose expansion cohorts have evaluable data

  Threshold and MD Anderson Cancer Center to evaluate patient safety data to determine proper dose

  Approximately 8-12 months

Secondary Outcomes (3)

• Maximum tolerated dose (MTD) of this therapy based on number of dose limiting toxicities that occur during the dose escalation phase

  Approximately 4-6 months

• Number of participants with treatment related adverse events

  Approximately 2 years

• Change from tumor diameter baseline

  Approximately 2 years

Study Arms (1)

Evofosfamide plus Ipilimumab

EXPERIMENTAL

Ipilimumab to be administered at same dose. Evofosfamide dose to be determined during duration of trial

Drug: Evofosfamide; Drug: Ipilimumab

Interventions

Evofosfamide DRUG

Evofosfamide given on day one and in combination with Ipilimumab on day 8 of the first two cycles, Ipilimumab given alone on day 8 of last two cycles for a total of four 21 day dosing cycles.

Evofosfamide plus Ipilimumab

Ipilimumab DRUG

Evofosfamide given on day one and in combination with Ipilimumab on day 8 of the first two cycles, Ipilimumab given alone on day 8 of last two cycles for a total of four 21 day dosing cycles.

Evofosfamide plus Ipilimumab

Eligibility Criteria

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

You may qualify if:

• Patients must be willing and able to review, understand, and provide written consent before study enrollment
• Patients must have either a histologically-confirmed metastatic or locally advanced prostate cancer, metastatic pancreatic cancer, melanoma or human papillomavirus (HPV) negative squamous cell carcinoma of head and neck.
• At least 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Karnofsky \> 60 %)
• Measurable disease as defined by irRECIST. Patients with castrate-resistant prostate cancer can have measurable or evaluable disease. Patients with evaluable disease must have documented evidence of progressive disease as defined by any of the following:
• Prostate-specific antigen (PSA) progression: minimum of 2 rising values (3 measurements) obtained a minimum of 7 days apart with the last result being at least \>/= 1.0 ng/mL;
• New or increasing non-bone disease (RECIST 1.1 criteria);
• Positive bone scan with 2 or more new lesions (PCWG3)
• Adequate bone marrow function within 7 days and defined as:
• White Blood Cell (WBC) ≥ 2500 cells/mm3
• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3cells
• Absolute lymphocyte count (ALC) \>1000 cells/mm3
• Hemoglobin ≥ 9 g/dL
• Platelets (PLT) ≥ 75,000 cells/mm3
• Acceptable renal function within 7 days defined as serum creatinine ≤ 2.0 times the institutional upper limit of normal (ULN) or calculated creatinine clearance ≥ 50 mL/min (by the Cockcroft Gault formula).

You may not qualify if:

• Active/uncontrolled autoimmune disease: patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], Systemic Lupus Erythematosus or autoimmune vasculitis \[e.g., Wegener's Granulomatosis\] are excluded from this study.
• Patients with history of any Grade 3 or Grade 4 adverse events from prior ipilimumab therapy, if administered in the past.
• Patients with history of mild autoimmune disorders - including but not limited to - mild psoriasis or Hashimoto's hypothyroidism, may be included at the discretion of the principle investigator.
• History of acute diverticulitis, intra-abdominal abscess, GI obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation.
• Patients on long term systemic steroids (\>10 mg daily prednisone equivalent). Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, or conditions not expected to recur in the absence of an external trigger are permitted to enroll at the discretion of the principle investigator. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.
• Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of AEs: e.g. a condition associated with frequent diarrhea or chronic skin conditions, recent surgery or colonic biopsy from which the patient has not recovered, or partial endocrine organ deficiencies.
• History of risk factors for TdP, including family history of long QT syndrome.
• Sustained systolic blood pressure (BP) \>140 mm Hg or \<90 mm Hg, diastolic BP \>100 mm Hg or \<60 mm Hg
• Patients with newly diagnosed, uncontrolled and or untreated cancer; related central nervous system diseases are excluded.
• Uncontrolled intercurrent illness, including, but not limited to, myocardial infarction within 6 months, unstable symptomatic ischemic heart disease, active uncontrolled infection requiring systemic therapy, or psychiatric illness/social situations that would limit compliance with study requirements.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days of day 1 of therapy.
• Current evidence of active and uncontrolled infection, NYHA Class III-IV CHF, documented Child's class B and C cirrhosis, active pancreatitis or uncontrolled medical disease which in the opinion of the investigator could compromise assessment of efficacy.
• Known human immunodeficiency virus (HIV)-positive unless on highly active antiretroviral therapy (HAART), and/or known Hepatitis B or C on treatment. Drug interactions between those agents and these experimental agents are wholly unknown (screening not required).
• Known hypersensitivity to the components of study drugs, its analogs, or drugs of similar chemical or biologic composition.
• Any live vaccine or non-oncology vaccine therapy used for prevention of infectious diseases (for up to one month prior to or after any dose of ipilimumab).

Sponsors & Collaborators

• Threshold Pharmaceuticals: lead
• M.D. Anderson Cancer Center: collaborator

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms; Melanoma; Squamous Cell Carcinoma of Head and Neck; Prostatic Neoplasms; Hypoxia

Interventions

TH 302; Ipilimumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• David Hong, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kristen L. Quigley

CONTACT

650-455-9622; kquigley@thresholdpharm.com

Thomas F. Wilson

CONTACT

302-359-0565; twilson@thresholdpharm.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: During the initial phase of the study a maximum tolerated dose will be determined based on the dose escalation scheme in the protocol. Once this dose is established, enrollment will be expanded for each of the 4 disease cohorts at that dose level.

Study Record Dates

• First Submitted: March 22, 2017
• First Posted: March 31, 2017
• Study Start: May 10, 2017
• Primary Completion: January 1, 2019
• Study Completion: April 1, 2019
• Last Updated: October 30, 2017

Record last verified: 2017-10

Locations

US (1)