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Pancreatic CancerPhase 1/2NCT02352831

Tosedostat With Capecitabine in Patients With Metastatic Pancreatic Adenocarcinoma

A Phase 1/2 study testing Tosedostat, Capecitabine and Fresh tissue biopsy in people with Pancreatic Cancer and Cancer of Pancreas, run by Washington University School of Medicine at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

There are two parts to this study: the goal of the first part of the study is to find the best dose of tosedostat when given in combination with capecitabine. The goal of the second part of the study is to look at how participants respond to treatment with tosedostat and capecitabine. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Tosedostat, Capecitabine and Fresh tissue biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
1 siteUnited States
Study dates
31 Aug 2015to 19 Oct 2018
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Histologically or cytologically proven metastatic or inoperable pancreatic adenocarcinoma.
  • Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >10 mm with CT scan or MRI, as >20 mm by chest x-ray, or >10 mm with calipers by clinical exam.
  • Must have progressed on, been intolerant to, or refused gemcitabine-based therapy.
  • At least 18 years of age.
  • ECOG performance status ≤ 2
  • Normal bone marrow and organ function as defined below:
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  • Absolute neutrophil count ≥ 1,000/mcl
  • Platelets ≥ 100,000/mcl
  • Total bilirubin ≤ 2.0 mg/dL
  • Creatinine ≤ 2.0 mg/dL
  • AST or ALT ≤2.5 IULN (≤5X IULN if liver metastases are present)
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Who cannot join

  • Chemotherapy < 2 weeks prior to the first planned dose of study treatment.
  • Radiotherapy < 3 weeks prior to the first planned dose of study treatment.
  • A history of other malignancy ≤ 2 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
  • Currently receiving any other investigational agents.
  • Known brain metastases. Patients with known brain metastases must be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to tosedostat or capecitabine or other agents used in the study.
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  • Previous treatment with any aminopeptidase inhibitor.
  • Previous exposure to either 5-FU or capecitabine at a systemic dose except for use in concurrent chemoradiation.
  • Known dihydropyrimidine dehydrogenase (DPD) deficiency or severe renal impairment (creatinine clearance < 30 mL/min by Cockcroft-Gault formula), as this would preclude use of capecitabine.
  • Significant cardiovascular disease defined as:
  • Myocardial infarction within 6 months of screening.
  • Unstable angina pectoris
  • Uncontrolled or clinically significant arrhythmia Grade ≥ 2
  • LVEF ≤ below institutional limits at screening
  • Congestive heart failure NYHA class III or IV
  • Presence of clinically significant valvular heart disease
  • Baseline troponin I or T > IULN and b-type natriuretic peptide > IULN.
  • Prior exposure to cardiotoxic agent, such as anthracyclines, within 3 months of enrollment.
  • Patient must have a QTc interval on ECG ≤ 0.48 seconds by Bazett's calculation at screening.
  • Patient may not be taking any drugs that prolong the QT/QTc interval. If patient is on any of these drugs, patient may enroll in the study if the drugs can be discontinued for at least 5 half-lives prior to the first dose of tosedostat and capecitabine.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant and/or breastfeeding. Patients that are of childbearing age must have a negative pregnancy test at screening and agree on using contraception during the duration of the study.
  • Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with tosedostat or capecitabine. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: Phase I/II Study Combining Tosedostat With Capecitabine in Patients With Metastatic Pancreatic Adenocarcinoma

There are two parts to this study: the goal of the first part of the study is to find the best dose of tosedostat when given in combination with capecitabine. The goal of the second part of the study is to look at how participants respond to treatment with tosedostat and capecitabine.

Being tested
Tosedostat, Capecitabine, Fresh tissue biopsy
Medical subject headings
Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TosedostatDrug

  • CapecitabineDrug

    Also called Xeloda

  • Fresh tissue biopsyProcedure or surgery

    Patients who have a partial response at the end of cycle 2 will be required to undergo biopsy if deemed safe for the patient and tissue is feasible to obtain.

Study groups in NCT02352831
Study groupRoleWhat they receive
Phase I (tosedostat + capecitabine)Experimental* The phase I study will be conducted in the standard 6-patient-per-cohort dose de-escalation fashion. * Tosedostat by mouth daily Days 1-21 of each 21-day cycle. Dose Level 0 (starting dose) = 120 mg PO daily and Dose Level -1 = 60 mg PO daily. All 6 patients in the Phase 1 received 120 mg starting dose of tosedostat. * Capecitabine 1000 mg/m^2 by mouth BID Days 1-14 of each 21-day cycle * Fresh tissue biopsy: Patients who have a partial response at the end of cycle 2 will be required to undergo biopsy if deemed safe for the patient and tissue is feasible to obtain.
Receives: Drug: Tosedostat; Drug: Capecitabine; Procedure: Fresh tissue biopsy
Phase II (tosedostat + capecitabine)Experimental* Tosedostat (dose determined by Phase I portion of study) by mouth daily Days 1-21 of each 21-day cycle * Capecitabine by mouth BID Days 1-14 of each 21-day cycle
Receives: Drug: Tosedostat; Drug: Capecitabine; Procedure: Fresh tissue biopsy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I Only: Recommended Phase II Dose of Tosedostat

    The recommended phase 2 dose (RP2D) is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle. If 0 or 1 of 6 patients in Dose Level 1 experience DLT during the first cycle, Dose Level 1 will be presumed to be the RP2D.

    DLTs are followed through completion of the first cycle.

    Measured: Completion of cycle 1 of all participants in Phase I portion of study (approximately 14 months)

  2. Phase I Only: Number of Participants Who Experience Dose-limiting Toxicities (DLTs)

    • Possibly/probably/definitely related to study treatment in 1st cycle (cyc) *Grade (Gr) 4 neutropenia >7 day, Febrile neutropenia of any duration with temperature ≥ 38.5 °C, Gr 4 anemia requires transfusion therapy on more than 2 occasions in 7 days, Gr 4 thrombocytopenia
    • Possibly/probably/definitely related gr. 3/4 non-hematologic toxicity that occurs 1st cyc with the following EXCEPTIONS:
    • Gr 3 nausea/vomiting/diarrhea/anorexia <72 hours that returns to Gr 1 prior to the start of cyc 2, Gr 3 hand-foot syndrome will only be considered a DLT for patients who have received 1 week of supportive care treatment with no improvement, Gr 3 fatigue that returns to Gr 1 prior to the start of cyc 2, Gr 3 flu-like symptoms <72 hours that returns to Gr 1 prior to start of cyc 2, Gr 3 arthralgia or myalgias <72 hours that return to Gr 1 prior to the start of cyc 2, Gr 3 potassium/phosphorus/magnesium that is asymptomatic or of non-clinical significance <72 hours, Gr 3 hypoalbuminemia

    Measured: Completion of cycle 1 of all participants in Phase I portion of study (approximately 14 months)

  3. Progression-free Survival (PFS) Rate

    • PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
    • Progressive disease (PD)
    • Target lesions: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
    • Non target lesions: Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.

    Measured: 3 months

Secondary outcomes (4)

  1. Overall Response Rate (ORR)

    • ORR = Complete response + partial response
    • Target lesions
    • Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
    • Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
    • Non target lesions *Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis).

    Measured: Up to 18 months

  2. Time-to-progression (TTP)

    -Progressive disease (PD)

    • Target lesions: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
    • Non target lesions: Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase

    Measured: Up to 24 months

  3. Overall Survival Rate (OS)

    Measured: Up to 1 year from completion of treatment (median treatment length 81.50 days (28.00-346.00)

  4. Number of Participants With a CA19-9 Response

    • CA19-9 is a tumor marker that is used in the management of pancreatic cancer. Rising CA19-9 levels may mean the tumor is growing and decreasing CA19-9 levels may mean the tumor is shrinking or the amount of cancer in the body is decreasing
    • A CA19-9 response means that the tumor marker has decreased over baseline (before treatment started) levels

    Measured: Completion of treatment (median treatment length 81.50 days (28.00-346.00)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Feb 2015 (estimated)
  2. Study start31 Aug 2015
  3. Primary completion20 Oct 2017
  4. Study completion19 Oct 2018

Why it stopped: Insufficient funding and drug supply from manufacturer

Resources

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02352831
Sponsor's protocol ID
201503074
Status last verified
Aug 2019
First submitted
28 Jan 2015
Last updated
28 Aug 2019
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tosedostat, Capecitabine and Fresh tissue biopsy in people with Pancreatic Cancer and Cancer of Pancreas, run by Washington University School of Medicine 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 13 inclusion and 23 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 28 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 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Phase I Only: Recommended Phase II Dose of Tosedostat (time frame: Completion of cycle 1 of all participants in Phase I portion of study (approximately 14 months)). The study lists 3 primary outcomes in all. 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 NCT02352831.

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 28 Aug 2019.

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