Pancreatic Ductal AdenocarcinomaEarly Phase 1NCT03481920
A Trial of PEGPH20 in Combination With Avelumab in Chemotherapy Resistant Pancreatic Cancer
A Early Phase 1 study testing PEGylated Recombinant Human Hyaluronidase (PEGPH20) and Avelumab in people with Pancreatic Ductal Adenocarcinoma and Pancreatic Cancer, run by PH Research, S.L. at 3 sites in Spain.
Trial summary
The purpose of this study is to evaluate the pharmacodynamics, safety and efficacy of PEGPH20 in combination with Avelumab in adult patients with chemotherapy resistant advanced or locally advanced pancreatic ductal adenocarcinoma (PDAC). This is a multi-center, open-label, non-randomized trial. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Ductal Adenocarcinoma, Pancreatic Cancer
- What is being tested?
- PEGylated Recombinant Human Hyaluronidase (PEGPH20) and Avelumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 3 sitesSpain
- Study dates
- 10 Jan 2018to 10 Jun 2019
- Phase
- Early 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
- Signed, written IRB/IEC-approved Informed Consent Form
- Histologically or cytologically-confirmed pancreatic ductal adenocarcinoma (PDAC).
- Accessible tumor for two repeated tumor biopsies.
- Progression to first line treatment for locally advanced or advanced disease. Prior adjuvant chemotherapy or chemoradiation therapy for early disease is allowed.
- Age ≥18 years.
- Radiologically measurable disease per RECIST v1.1.
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- Performance-status ECOG 0 -2.
- Life expectancy ≥ 3 months.
- Resolved acute effects of any prior therapy to baseline or Grade ≤1 severity
- Screening laboratory:
- Hematologic: ANC ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL
- Hepatic: Total bilirubin level ≤ 1.5 × the ULN range and AST and ALT levels ≤ 2.5 × ULN or AST and ALT levels ≤ 5 X ULN (for subjects with documented metastatic disease to the liver)
- Renal: Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula or serum creatinine ≤ 2.0 mg/dL.
- Albumin ≥2.5 g/dL.
- Coagulation: PT time and INR within normal limits (+/-15%). PTT within normal limits (+/-15%).
- If a subject requires anticoagulation, treatment must be modified to enoxaparin.
- Negative serum pregnancy test if female subject is of childbearing potential.
- Patients who are willing and able to comply with scheduled visits, treatment plans, laboratory tests, biopsies when required, and other procedures.
Who cannot join
- Clinical evidence of DVT, PE, prior history of CVA or history of TIA within 12 months or other known TE event present during the screening period
- Current use of megestrol acetate (use within 10 days of Day 1).
- Contraindication to heparin as per institutional guidelines.
- Another primary cancer within the last 3 years currently requiring antineoplastic treatment within the exception of non-melanoma skin cancer, early-stage prostate cancer, or curatively treated cervical carcinoma in-situ.
- Current use of immunosuppressive medication within 2 weeks of study participation, EXCEPT for those listed in protocol
- Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent: Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
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- Prior organ transplantation including allogenic stem-cell transplantation.
- Active infection requiring systemic therapy.
- Known infection with human immunodeficiency virus, Hepatitis B, or Hepatitis C
- Known prior severe hypersensitivity to investigational product, hyaluronidase, or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3).
- Any history of anaphylaxis or uncontrolled asthma (that is, 3 or more features of partially controlled asthma).
- Clinically significant (i.e., active) cardiovascular disease: myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
- Prior cerebrovascular accident/stroke.
- Clinically significant carotid artery disease (e.g. prior carotid surgery, symptomatic and/or requires treatment)
- Inability to comply with study and follow-up procedures as judged by the Investigator.
- Known alcohol or drug abuse.
Trial locations and contacts
3 sites in 1 country.
Spain3 sites
Hospital Universitario Fuenlabrada
Fuenlabrada, Madrid
Hospital Universitario La Paz
Madrid, 28046
Hospital Ramon y Cajal
Madrid
About this study
Official title: A Pilot Trial of PEGPH20 (Pegylated Hyaluronidase) in Combination With Avelumab (Anti-PD-L1 MSB0010718C) in Chemotherapy Resistant Pancreatic Cancer
The purpose of this study is to evaluate the pharmacodynamics, safety and efficacy of PEGPH20 in combination with Avelumab in adult patients with chemotherapy resistant advanced or locally advanced pancreatic ductal adenocarcinoma (PDAC). This is a multi-center, open-label, non-randomized trial.
Read the detailed description
The reported response rate with check-point inhibitors in PDAC is 0 %. This study tests the hypothesis that elimination of HA in pancreas tumor microenvironment mediated by PEG PH20 will result in increased tumor vascularization and vessel patency as well as stromal remodeling with increase immune infiltrate. These effects may facilitate the activity of check-point inhibitors like avelumab by at least two mechanisms including increase in drug delivery and increasing immune infiltrate.
The purpose of this study is to evaluate the pharmacodynamics, safety and efficacy of PEGPH20 in combination with Avelumab in adult patients with chemotherapy resistant advanced or locally advanced pancreatic ductal adenocarcinoma (PDAC). This is a multi-center, open-label, non-randomized trial.
- Being tested
- PEGylated Recombinant Human Hyaluronidase (PEGPH20), Avelumab
- Keywords
- pancreatic cancer, inmunotherapy
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PEGylated Recombinant Human Hyaluronidase (PEGPH20)Drug
PEGPH20 will be administered at a dose of 3.0 micrograms per kilogram (μg/kg) as an intravenous (IV) infusion.
AvelumabDrug
Also called MSB0010718C
Avelumab will be administered as at a dose of 10 milligrams per kilogram (mg/kg) as an intravenous (IV) infusion once every 2 weeks.
| Study group | Role | What they receive |
|---|---|---|
| PEGPH20 + Avelumab | Experimental | PEGPH20, a multi-site PEGylated enzyme generated by conjugating N-hydroxysuccinimidyl ester of methoxypoly(ethylene glycol)-butanoic acid (MSBA30K/B or PEG) and recombinant human hyaluronidase (rHuPH20). PEGPH20 has a half-life of approximately 2 days, thereby enabling systemic activity and sustained duration of action to degrade HA. In many different tumor types tested in murine xenograft models, response to PEGPH20 has been shown to be more robust for tumors characterized by higher HA expression. Receives: Drug: PEGylated Recombinant Human Hyaluronidase (PEGPH20); Drug: Avelumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine ORR as per RECIST v1.1 criteria
Determine ORR as per RECIST v1.1 criteria
Measured: 6 months from trial treatment initiation cycle 1/day 1. Each treatment cycle is 14 days
To assess the safety of this combination in patients with PDAC.
graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03
Measured: Initiation of trial treatment cycle 1/day 1 through 30 days after last dose of trial treatment
Secondary outcomes (3)
Determine OS (OVERALL SURVIVAL)
The length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that patients diagnosed with the disease are still alive
Measured: From date of treatment initiation cycle 1/day 1 until death from any cause, assessed up to 36 months
Determine PFS (PROGRESSION FREE SURVIVAL)
The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse.
Measured: From date of treatment initiation cycle 1/day 1 until progression, assessed up to 24 months
Changes in CA 19,9 leves
Measured in UI/ML
Measured: Up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2018
- Study start10 Jan 2018
- Primary completion10 Jan 2019
- Study completion10 Jun 2019
Why it stopped: Stopped Enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreatic Ductal AdenocarcinomaStudies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- PH Research, S.L.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03481920
- Sponsor's protocol ID
- PH1603
- Status last verified
- Jan 2019
- First submitted
- 10 Feb 2018
- Last updated
- 22 Aug 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Trial of PEGPH20 (Pegylated Hyaluronidase) in Combination With Avelumab (Anti-PD-L1 MSB0010718C) in Chemotherapy Resistant Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT03481920
- Acronym / sponsor ID
- PH1603
- Keywords
- pancreatic cancer, inmunotherapy
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Stopped Enrollment
- Enrolment
- 7 participants (actual)
- Lead sponsor
- PH Research, S.L.University, hospital or other
- Study start
- 10 Jan 2018 (actual)
- Primary completion
- 10 Jan 2019 (actual)
- Study completion
- 10 Jun 2019 (actual)
- First posted
- 29 Mar 2018 (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.
The purpose of this study is to evaluate the pharmacodynamics, safety and efficacy of PEGPH20 in combination with Avelumab in adult patients with chemotherapy resistant advanced or locally advanced pancreatic ductal adenocarcinoma (PDAC). This is a multi-center, open-label, non-randomized trial.
Detailed description
The reported response rate with check-point inhibitors in PDAC is 0 %. This study tests the hypothesis that elimination of HA in pancreas tumor microenvironment mediated by PEG PH20 will result in increased tumor vascularization and vessel patency as well as stromal remodeling with increase immune infiltrate. These effects may facilitate the activity of check-point inhibitors like avelumab by at least two mechanisms including increase in drug delivery and increasing immune infiltrate.
The purpose of this study is to evaluate the pharmacodynamics, safety and efficacy of PEGPH20 in combination with Avelumab in adult patients with chemotherapy resistant advanced or locally advanced pancreatic ductal adenocarcinoma (PDAC). This is a multi-center, open-label, non-randomized trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PEGPH20 + Avelumab | Experimental | Drug: PEGylated Recombinant Human Hyaluronidase (PEGPH20), Drug: AvelumabPEGPH20, a multi-site PEGylated enzyme generated by conjugating N-hydroxysuccinimidyl ester of methoxypoly(ethylene glycol)-butanoic acid (MSBA30K/B or PEG) and recombinant human hyaluronidase (rHuPH20). PEGPH20 has a half-life of approximately 2 days, thereby enabling systemic activity and sustained duration of action to degrade HA. In many different tumor types tested in murine xenograft models, response to PEGPH20 has been shown to be more robust for tumors characterized by higher HA expression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Signed, written IRB/IEC-approved Informed Consent Form
- Histologically or cytologically-confirmed pancreatic ductal adenocarcinoma (PDAC).
- Accessible tumor for two repeated tumor biopsies.
- Progression to first line treatment for locally advanced or advanced disease. Prior adjuvant chemotherapy or chemoradiation therapy for early disease is allowed.
- Age ≥18 years.
Key exclusion criteria (16 listed)
- Clinical evidence of DVT, PE, prior history of CVA or history of TIA within 12 months or other known TE event present during the screening period
- Current use of megestrol acetate (use within 10 days of Day 1).
- Contraindication to heparin as per institutional guidelines.
- Another primary cancer within the last 3 years currently requiring antineoplastic treatment within the exception of non-melanoma skin cancer, early-stage prostate cancer, or curatively treated cervical carcinoma in-situ.
- Current use of immunosuppressive medication within 2 weeks of study participation, EXCEPT for those listed in protocol
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 |
|---|---|---|
| PEGylated Recombinant Human Hyaluronidase (PEGPH20)PEGPH20 will be administered at a dose of 3.0 micrograms per kilogram (μg/kg) as an intravenous (IV) infusion. | Drug | PEGPH20 + Avelumab |
| AvelumabAlso: MSB0010718CAvelumab will be administered as at a dose of 10 milligrams per kilogram (mg/kg) as an intravenous (IV) infusion once every 2 weeks. | Drug | PEGPH20 + Avelumab |
Primary outcome
Determine ORR as per RECIST v1.1 criteria
Time frame: 6 months from trial treatment initiation cycle 1/day 1. Each treatment cycle is 14 days
Determine ORR as per RECIST v1.1 criteria
To assess the safety of this combination in patients with PDAC.
Time frame: Initiation of trial treatment cycle 1/day 1 through 30 days after last dose of trial treatment
graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03
3 secondary outcomes
Determine OS (OVERALL SURVIVAL)
Time frame: From date of treatment initiation cycle 1/day 1 until death from any cause, assessed up to 36 months
Determine PFS (PROGRESSION FREE SURVIVAL)
Time frame: From date of treatment initiation cycle 1/day 1 until progression, assessed up to 24 months
Changes in CA 19,9 leves
Time frame: Up to 4 weeks
Results and safety
The study was stopped early (reason given: Stopped Enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2019.
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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.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing PEGylated Recombinant Human Hyaluronidase (PEGPH20) and Avelumab in people with Pancreatic Ductal Adenocarcinoma and Pancreatic Cancer, run by PH Research, S.L. at 3 sites in Spain.
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 18 inclusion and 16 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: stopped early, as of the sponsor's last update on 22 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Spain. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Stopped Enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine ORR as per RECIST v1.1 criteria (time frame: 6 months from trial treatment initiation cycle 1/day 1. Each treatment cycle is 14 days). The study lists 2 primary outcomes in all. 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 22 Aug 2019.