CYP3A InhibitorPhase 1IntenSifyNCT05494866
A Trial of Cobicistat and Gemcitabine and Nab-Paclitaxel in Patients with Advanced Stage or Metastatic Pancreatic Ductal Adenocarcinoma
A Phase 1 study testing Cobicistat Oral Tablet, Gemcitabin and Nab paclitaxel in people with CYP3A Inhibitor and Advanced Stage or Metastatic Pancreatic Ductal Adenocarcinoma, run by German Cancer Research Center at 1 site in Germany.
Trial summary
To explore the possibility to overcome CYP3A-mediated resistance to anticancer drugs in pancreatic cancer, we will investigate the pharmacokinetics, safety, tolerability, and efficacy of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in combination with gemcitabine and the CYP3A inhibitor cobicistat in a phase… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CYP3A Inhibitor, Advanced Stage or Metastatic Pancreatic Ductal Adenocarcinoma, Pancreatic Cancer
- What is being tested?
- Cobicistat Oral Tablet, Gemcitabin and Nab paclitaxel
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteGermany
- Study dates
- 7 Dec 2022to 15 Mar 2024
- 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
- Age ≥18 years
- Histologically or cytologically confirmed ductal adenocarcinoma of the pancreas.
- Metastatic disease. Advanced stage locally advanced, unresectable (patients that are resectable but refuse the operation are not eligible) may be eligible after discussion with the medical representative of the sponsor
- Eligible for therapy with gemcitabine / nab-paclitaxel according to standard of care / local therapeutic standard (in any palliative therapy line)
- Performance score ECOG 0-2
- Adequate organ function defined as:
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- Adequate hematologic function (WBC ≥3000/µL, absolute neutrophil count ≥1500/µL, platelets ≥100.000/µL, hemoglobin ≥8 g/dL)
- Adequate renal function (estimated glomerular filtration rate ≥30 mL/min)
- Adequate liver function (serum bilirubin ≤1.5 x ULN, AST/ALT ≤2.5 x ULN, or 5 x ULN if hepatic metastases are present)
- Prothrombintime (PT) <1.1 ULN, partial thromboplastin time <1.1 ULN, INR <1.1 ULN.
- Use of reliable contraception with a Pearl Index <1% (i.e. two independent effective contraceptive methods) during the trial and for two weeks after the last administration of trial medication in men or women of child bearing potential (WOCBP).
- Measurable disease according to RECIST 1.1 criteria.
- Patient willing to undergo tumor biopsy. This requires a tumor lesion accessible for a biopsy. In patients without an accessible tumor lesion the patient may be enrolled and tumor biopsy waived after discussion with the sponsor's medical representative.
- Available CT scan of thorax and abdomen not older than 30 days before start of treatment (day 1 of cycle 1). Patients that cannot have a CT scan because of medical reasons (e.g. allergy to contrast dye) may be eligible after MRIs as per standard of care to stage the patient and after documented consultation with the sponsor.
- Ability to understand character, consequences and requirements of the clinical trial and to comply with the study protocol and dosing regimen.
Who cannot join
- Presence of brain metastases, unless previously treated and well-controlled for at least 3 months (defined as clinically stable, no edema, no steroids and stable in 2 scans at least 4 weeks apart).
- Testing positive against human immunodeficiency virus (HIV) or history thereof
- Active hepatitis C virus (HCV) infection (patients with status post-infection after eradication through antiviral therapy are eligible)
- Uncontrolled hepatitis B virus (HBV) infection (<3 months of treatment with a nucleotide analogue and/or >100 HBV-DNA particles)
- Pre-existing, clinically significant peripheral neuropathy, defined as CTCAE grade 2 or higher neurosensory or neuromotor toxicity, regardless of etiology
- History of malignancy other than pancreatic cancer in the last 5 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Patients with other malignancies are eligible if they were cured by surgery alone or surgery plus radiotherapy and have been continuously disease-free for at least 5 years.
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- Present treatment with phenprocoumon, warfarin or another coumadine-based anticoagulant.
- Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
- Major surgery, other than for diagnostic purposes ((done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 of treatment in this study.
- History of allergy or hypersensitivity to any of the study drugs or any of their excipients.
- Serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders, which could compromise patient's safety or study data integrity.
- Participation in any other interventional clinical protocol or investigational trial.
- Unwillingness or inability to comply with study procedures.
- Therapy with a narrow therapeutic index drug that is substrate of CYP3A, CYP2D6, or CYP2C9 whose dose cannot be appropriately adjusted.
- Therapy with any medications or substances that are inhibitors or inducers of CYP450 3A enzyme(s) or therapy with medication that is contraindicated when taking Tybost
- Pregnancy or lactating
Trial locations and contacts
1 site in 1 country.
Germany1 site
University Hospital Heidelberg
Heidelberg, Baden-Wurttemberg, 69120
About this study
Official title: IntenSify: an Open-label Phase I Trial of the CYP3A Inhibitor Cobicistat and the Cytostatics Gemcitabine and Nab-Paclitaxel in Patients with Advanced Stage or Metastatic Pancreatic Ductal Adenocarcinoma to Evaluate the Combination's Pharmacokinetics, Safety and Efficacy
To explore the possibility to overcome CYP3A-mediated resistance to anticancer drugs in pancreatic cancer, we will investigate the pharmacokinetics, safety, tolerability, and efficacy of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in combination with gemcitabine and the CYP3A inhibitor cobicistat in a phase I proof-of-concept trial to determine the safety profile, the recommended dose of nab-paclitaxel in combination with gemcitabine and cobicistat, and to determine whether there is an early efficacy signal warranting a larger scale trial.
The present trial is an open-label trial consisting of a dose-escalation part and an expansion part. The dose escalation part is designed to determine the safety, tolerability, and pharmacokinetics of nab-paclitaxel in combination with gemcitabine and cobicistat and will guide the dosing in the expansion part of the trial.
Read more
The trial enrolls patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma and adequate performance score (ECOG PS 0-2) who would usually receive gemcitabine and nab-paclitaxel according to standard of care.
Primary endpoint for the phase I trial is the safety of the combination. Overall survival (OS), disease control rate (DCR), overall response rate (ORR), duration of response (DoR) and progression free survival (PFS) are secondary efficacy endpoints. Further secondary endpoints are tolerability, pharmacokinetics, pharmacodynamics, and pharmacogenomics.
- Conditions
- CYP3A Inhibitor, Advanced Stage or Metastatic Pancreatic Ductal Adenocarcinoma, Pancreatic Cancer, Pancreatic Adenocarcinoma, Pancreatic Neoplasm
- Being tested
- Cobicistat Oral Tablet, Gemcitabin, Nab paclitaxel
- Keywords
- CYP3A Inhibitor, Pancreatic Ductal Adenocarcinoma, Adenocarcinoma, Carcinoma, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Neoplasms, Cobicistat, Anti-HIV Agents, Anti-Retroviral Agents, Antiviral Agents, Anti-Infective Agents, Cytochrome P-450 CYP3A Inhibitors, Cytochrome P-450 Enzyme Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action
- Medical subject headings
- Pancreatic Neoplasms, Adenocarcinoma, Carcinoma, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cobicistat Oral TabletDrug
Cobicistat Oral Tablet
GemcitabinDrug
Gemcitabin
Nab paclitaxelDrug
nab-Paclitaxel
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | CYP3A Inhibitor Cobicistat and the cytostatics Gemcitabine and nab-Paclitaxel Receives: Drug: Cobicistat Oral Tablet; Drug: Gemcitabin; Drug: Nab paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
occurrence of DLTs
occurrence of DLTs within treatment cycle 1
Measured: Day 1 to day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2022
- Study start7 Dec 2022
- Primary completion15 Mar 2024
- Study completion15 Mar 2024
Why it stopped: lack of efficacy paired with high toxicity
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CYP3A InhibitorStudies 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
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- German Cancer Research Center
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital Heidelberg
- Responsible party
- Sponsor
- Investigators
- Nicolas Hohmann, PD Dr. med., Principal investigator, University Hospital Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05494866
- Sponsor's protocol ID
- NH21
- Other IDs
- 2019-001439-29, 2019
- Acronym
- IntenSify
- Status last verified
- Mar 2025
- First submitted
- 8 Aug 2022
- Last updated
- 25 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Hohmann N, Sprick MR, Pohl M, Ahmed A, Burhenne J, Kirchner M, Le Cornet L, Kratzmann M, Hajda J, Stenzinger A, Steindorf K, Delorme S, Schlemmer HP, Riethdorf S, van Schaik R, Pantel K, Siveke J, Seufferlein T, Jager D, Haefeli WE, Trumpp A, Springfeld C. Protocol of the IntenSify-Trial: An open-label phase I trial of the CYP3A inhibitor cobicistat and the cytostatics gemcitabine and nab-paclitaxel in patients with advanced stage or metastatic pancreatic ductal adenocarcinoma to evaluate the combination's pharmacokinetics, safety, and efficacy. Clin Transl Sci. 2023 Dec;16(12):2483-2493. doi: 10.1111/cts.13661. Epub 2023 Nov 3.
PubMed 37920921
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- IntenSify: an Open-label Phase I Trial of the CYP3A Inhibitor Cobicistat and the Cytostatics Gemcitabine and Nab-Paclitaxel in Patients with Advanced Stage or Metastatic Pancreatic Ductal Adenocarcinoma to Evaluate the Combination's Pharmacokinetics, Safety and Efficacy
- ClinicalTrials.gov ID
- NCT05494866
- Acronym / sponsor ID
- IntenSify / NH21
- Conditions
- CYP3A Inhibitor, Advanced Stage or Metastatic Pancreatic Ductal Adenocarcinoma, Pancreatic Cancer, Pancreatic Adenocarcinoma, Pancreatic Neoplasm
- Keywords
- CYP3A Inhibitor, Pancreatic Ductal Adenocarcinoma, Adenocarcinoma, Carcinoma, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Neoplasms, Cobicistat
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: lack of efficacy paired with high toxicity
- Enrolment
- 6 participants (actual)
- Lead sponsor
- German Cancer Research CenterUniversity, hospital or other
- Collaborators
- University Hospital Heidelberg
- Study start
- 7 Dec 2022 (actual)
- Primary completion
- 15 Mar 2024 (actual)
- Study completion
- 15 Mar 2024 (actual)
- First posted
- 10 Aug 2022 (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.
To explore the possibility to overcome CYP3A-mediated resistance to anticancer drugs in pancreatic cancer, we will investigate the pharmacokinetics, safety, tolerability, and efficacy of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in combination with gemcitabine and the CYP3A inhibitor cobicistat in a phase I proof-of-concept trial to determine the safety profile, the recommended dose of nab-paclitaxel in combination with gemcitabine and cobicistat, and to determine whether there is an early efficacy signal warranting a larger scale trial.
The present trial is an open-label trial consisting of a dose-escalation part and an expansion part. The dose escalation part is designed to determine the safety, tolerability, and pharmacokinetics of nab-paclitaxel in combination with gemcitabine and cobicistat and will guide the dosing in the expansion part of the trial.
The trial enrolls patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma and adequate performance score (ECOG PS 0-2) who would usually receive gemcitabine and nab-paclitaxel according to standard of care.
Primary endpoint for the phase I trial is the safety of the combination. Overall survival (OS), disease control rate (DCR), overall response rate (ORR), duration of response (DoR) and progression free survival (PFS) are secondary efficacy endpoints. Further secondary endpoints are tolerability, pharmacokinetics, pharmacodynamics, and pharmacogenomics.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Cobicistat Oral Tablet, Drug: Gemcitabin, Drug: Nab paclitaxelCYP3A Inhibitor Cobicistat and the cytostatics Gemcitabine and nab-Paclitaxel |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Age ≥18 years
- Histologically or cytologically confirmed ductal adenocarcinoma of the pancreas.
- Metastatic disease. Advanced stage locally advanced, unresectable (patients that are resectable but refuse the operation are not eligible) may be eligible after discussion with the medical representative of the sponsor
- Eligible for therapy with gemcitabine / nab-paclitaxel according to standard of care / local therapeutic standard (in any palliative therapy line)
- Performance score ECOG 0-2
Key exclusion criteria (16 listed)
- Presence of brain metastases, unless previously treated and well-controlled for at least 3 months (defined as clinically stable, no edema, no steroids and stable in 2 scans at least 4 weeks apart).
- Testing positive against human immunodeficiency virus (HIV) or history thereof
- Active hepatitis C virus (HCV) infection (patients with status post-infection after eradication through antiviral therapy are eligible)
- Uncontrolled hepatitis B virus (HBV) infection (<3 months of treatment with a nucleotide analogue and/or >100 HBV-DNA particles)
- Pre-existing, clinically significant peripheral neuropathy, defined as CTCAE grade 2 or higher neurosensory or neuromotor toxicity, regardless of etiology
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 |
|---|---|---|
| Cobicistat Oral TabletCobicistat Oral Tablet | Drug | Arm 1 |
| GemcitabinGemcitabin | Drug | Arm 1 |
| Nab paclitaxelnab-Paclitaxel | Drug | Arm 1 |
Primary outcome
occurrence of DLTs
Time frame: Day 1 to day 28
occurrence of DLTs within treatment cycle 1
Results and safety
The study was stopped early (reason given: lack of efficacy paired with high toxicity). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2025.
- Derived from this study: PubMed 37920921Hohmann N, Sprick MR, Pohl M, Ahmed A, Burhenne J, Kirchner M, Le Cornet L, Kratzmann M, Hajda J, Stenzinger A, Steindorf K, Delorme S, Schlemmer HP, Riethdorf S, van Schaik R, Pantel K, Siveke J, Seufferlein T, Jager D, Haefeli WE, Trumpp A, Springfeld C. Protocol of the IntenSify-Trial: An open-label phase I trial of the CYP3A inhibitor cobicistat and the cytostatics gemcitabine and nab-paclitaxel in patients with advanced stage or metastatic pancreatic ductal adenocarcinoma to evaluate the combination's pharmacokinetics, safety, and efficacy. Clin Transl Sci. 2023 Dec;16(12):2483-2493. doi: 10.1111/cts.13661. Epub 2023 Nov 3.
- Individual participant dataSharing planned: Undecided
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.
Nicolas Hohmann, PD Dr. med. principal investigator
University Hospital Heidelberg
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 Cobicistat Oral Tablet, Gemcitabin and Nab paclitaxel in people with CYP3A Inhibitor and Advanced Stage or Metastatic Pancreatic Ductal Adenocarcinoma, run by German Cancer Research Center at 1 site in Germany.
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 15 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 25 Mar 2025. 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 Germany. 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?
The study was stopped early (reason given: lack of efficacy paired with high toxicity). 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?
occurrence of DLTs (time frame: Day 1 to day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05494866, which also lists 1 linked publication.
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 25 Mar 2025.