Pancreatic CancerPhase 1NCT03098160
Immunotherapy Study of Evofosfamide in Combination With Ipilimumab
A Phase 1 study testing Evofosfamide and Ipilimumab in people with Pancreatic Cancer and Melanoma, run by Threshold Pharmaceuticals at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cancer, Melanoma, Squamous Cell Carcinoma of the Head and Neck
- What is being tested?
- Evofosfamide and Ipilimumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 69 participants
- Where
- 1 siteUnited States
- Study dates
- 10 May 2017to Apr 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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).
- Acceptable liver function within 7 days of day 1 of therapy defined as:
- • Bilirubin ≤ 1.5 times institutional ULN; does not apply to patients diagnosed with Gilbert's syndrome.
- • AST (SGOT) and ALT (SGPT) ≤ 3 times institutional ULN; if liver metastases are present, then ≤ 5 times ULN is allowed.
- QTc interval of ≤ 450 msec (males) or 470 msec (females) calculated according to Fridericia's formula (QTc = QT/RR0.33; RR=RR interval)
- Ability and availability to complete all prescribed biopsies (prior to the first evofosfamide dose and between day 15 of Cycle 2 and day 8 of Cycle 3)
- At least 3 weeks from previous cytotoxic chemotherapy or radiation therapy and at least 5 half-lives or 6 weeks, whichever is shorter, after targeted or biologic therapy excepting prior treatment with CTLA 4, PD-1, or PD-L1 blocking antibodies for which only a 2 week interval is required. Patients with prostate cancer, unless orchiectomy has been performed in them, may continue to receive androgen deprivation therapy (ADT), anti-androgen therapy or therapy that interferes with androgenic stimulation.
- Patients must have recovered from toxicity related to prior therapy to at least grade 1 (defined by CTCAE 4.0) or baseline level. Chronic stable grade 2 peripheral neuropathy secondary to neurotoxicity from prior therapies may be considered on a case by case basis by the Principal Investigator.
- Female patients of childbearing age must have a negative serum HCG test within 7 days of study enrollment, unless prior hysterectomy or menopause (defined as age ≥ 55 years and twelve consecutive months without menstrual activity). Female patients should not become pregnant or breast-feed while on this study.
- Sexually active male and female patients should use effective birth control (abstinence; hormonal or barrier method) for the duration of the study and at least 2 months from last dose.
Who cannot join
- 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.
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- Receiving QT-prolonging drugs with a risk of causing torsades de pointes (See Appendix E), unless ECG meets inclusion criteria on a stable dose of the drug and with discussion and agreement with the project clinician
- 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).
- Concomitant therapy with any of the following: IL-2, interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; or other investigational therapies.
- Receiving medications that are strong inhibitors or inducers of CYP3A4 (Appendix D).
- Use of any other concurrent investigational agents or anticancer agents including hormonal therapy, except in the case of prostate cancer patients who are being treated anti-androgen or bone targeting therapies.
- Female patients who have been on hormone replacement therapy (HRT) for menopausal symptoms for a period of at least 2 months will not be excluded from the study provided the HRT regimen remains unchanged during the conduct of the study.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Ly Nguyen, 713-563-2169, LMNguyen1@mdanderson.org
Dwana Sanders, dwsanders@mdanderson.org
About this study
Official title: A Phase 1 Immunotherapy Study of Evofosfamide in Combination With Ipilimumab in Patients With Advanced Solid Malignancies
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.
Read the detailed description
Tumor hypoxia can lead to poor effector T cell penetration and immunosuppressive signaling via myeloid-derived suppressor, myofibroblast and regulatory T cells. Disruption of these hypoxic regions within the tumor microenvironment by the hypoxia-directed cytotoxic agent evofosfamide may enhance the ability of the CTLA-4 checkpoint inhibitor ipilimumab to reject otherwise resistant solid tumors. Additionally, induction of immunogenic cell death of tumor cells by evofosfamide may enhance dendritic cell presentation of tumor antigens to lymphocytes in draining lymph nodes, leading to clonal expansion of tumor-specific T cells, especially in combination with ipilimumab.
- Conditions
- Pancreatic Cancer, Melanoma, Squamous Cell Carcinoma of the Head and Neck, Prostate Cancer
- Being tested
- Evofosfamide, Ipilimumab
- Keywords
- Immunotherapy, Hypoxia, Evofosfamide, Ipilimumab, TH-302
- Medical subject headings
- Pancreatic Neoplasms, Melanoma, Squamous Cell Carcinoma of Head and Neck, Prostatic Neoplasms, Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EvofosfamideDrug
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.
IpilimumabDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Evofosfamide plus Ipilimumab | Experimental | Ipilimumab to be administered at same dose. Evofosfamide dose to be determined during duration of trial Receives: Drug: Evofosfamide; Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Threshold and MD Anderson Cancer Center to evaluate patient safety data to determine proper dose
Measured: Approximately 4-6 months
Number of participants with treatment related adverse events
Safety grading based on CTCAE guidelines
Measured: Approximately 2 years
Change from tumor diameter baseline
Antitumor efficacy based on irRECIST
Measured: Approximately 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2017
- Study start10 May 2017
- Primary completionJan 2019 (estimated)
- Study completionApr 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 69 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Threshold Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- M.D. Anderson Cancer Center
- Responsible party
- Sponsor
- Investigators
- David Hong, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03098160
- Sponsor's protocol ID
- TH-CR-417
- Status last verified
- Oct 2017
- First submitted
- 22 Mar 2017
- Last updated
- 30 Oct 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Safety and efficacy data may be shared in the form of a paper or trials in progress poster at a conference. Additionally, data may be shared via the clinical study report.
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Immunotherapy Study of Evofosfamide in Combination With Ipilimumab in Patients With Advanced Solid Malignancies
- ClinicalTrials.gov ID
- NCT03098160
- Acronym / sponsor ID
- TH-CR-417
- Conditions
- Pancreatic Cancer, Melanoma, Squamous Cell Carcinoma of the Head and Neck, Prostate Cancer
- Keywords
- Immunotherapy, Hypoxia, Evofosfamide, Ipilimumab, TH-302
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 69 participants (estimated)
- Lead sponsor
- Threshold PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- M.D. Anderson Cancer Center
- Study start
- 10 May 2017 (actual)
- Primary completion
- Jan 2019 (estimated)
- Study completion
- Apr 2019 (estimated)
- First posted
- 31 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Tumor hypoxia can lead to poor effector T cell penetration and immunosuppressive signaling via myeloid-derived suppressor, myofibroblast and regulatory T cells. Disruption of these hypoxic regions within the tumor microenvironment by the hypoxia-directed cytotoxic agent evofosfamide may enhance the ability of the CTLA-4 checkpoint inhibitor ipilimumab to reject otherwise resistant solid tumors. Additionally, induction of immunogenic cell death of tumor cells by evofosfamide may enhance dendritic cell presentation of tumor antigens to lymphocytes in draining lymph nodes, leading to clonal expansion of tumor-specific T cells, especially in combination with ipilimumab.
Study design
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Evofosfamide plus Ipilimumab | Experimental | Drug: Evofosfamide, Drug: IpilimumabIpilimumab to be administered at same dose. Evofosfamide dose to be determined during duration of trial |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 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:
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EvofosfamideEvofosfamide 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. | Drug | Evofosfamide plus Ipilimumab |
| IpilimumabEvofosfamide 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. | Drug | Evofosfamide plus Ipilimumab |
Primary outcome
Recommended phase 2 dose (RP2D) determined after maximally tolerated dose is set and four dose expansion cohorts have evaluable data
Time frame: Approximately 8-12 months
Threshold and MD Anderson Cancer Center to evaluate patient safety data to determine proper dose
3 secondary outcomes
Maximum tolerated dose (MTD) of this therapy based on number of dose limiting toxicities that occur during the dose escalation phase
Time frame: Approximately 4-6 months
Number of participants with treatment related adverse events
Time frame: Approximately 2 years
Change from tumor diameter baseline
Time frame: Approximately 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2017.
- Individual participant dataSharing planned: Undecided. Safety and efficacy data may be shared in the form of a paper or trials in progress poster at a conference. Additionally, data may be shared via the clinical study report.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Hong, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Evofosfamide and Ipilimumab in people with Pancreatic Cancer and Melanoma, run by Threshold Pharmaceuticals at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kristen L. Quigley (650-455-9622, kquigley@thresholdpharm.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recommended phase 2 dose (RP2D) determined after maximally tolerated dose is set and four dose expansion cohorts have evaluable data (time frame: Approximately 8-12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2017.