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Transitional Cell Carcinoma of BladderPhase 2NCT01620970

PF-03446962 in Relapsed or Refractory Urothelial Cancer

A Phase 2 study testing PF03446962 in people with Transitional Cell Carcinoma of Bladder, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Salvage chemotherapy for advanced urothelial cancer (UC) yields suboptimal response rates of 15-40%, a median progression-free survival of 2-4 months and a median overall survival of 6 months. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Transitional Cell Carcinoma of Bladder
What is being tested?
PF03446962
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
1 siteItaly
Study dates
1 Mar 2012to 1 Jun 2013
Phase
Phase 2
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.
  • ECOG Performance status of 0 or 1.
  • Life expectancy of at least 12 weeks.
  • Measurable disease criteria (RECIST v1.1).
  • Histological diagnosis of urothelial cancer.
  • Locally advanced or metastatic disease.
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  • Failure of at least 1 prior chemotherapy regimen for metastatic disease.
  • Neoadjuvant/adjuvant therapy considered if relapse occurred within 6 months of the last cycle of chemotherapy.
  • Adequate bone marrow, liver and renal function requirements, to be conducted within 7 days prior to screening.

Who cannot join

  • Cardiovascular or CNS disease.
  • Previously untreated CNS metastases.
  • Active Hepatitis B, C, HIV infection.
  • Pregnant or breast-feeding patients.
  • GI abnormalities and any other clinical condition at high risk of bleeding.
  • Substance abuse and any other condition which may interfere with patient's participation in the study or evaluation of study results.

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan, 20133

Other trials in Italy

About this study

Official title: Phase II Study of the Fully Human Monoclonal Antibody Against Transforming Growth Factor-beta (TGFβ) Receptor ALK1 (PF-03446962) in Relapsed or Refractory Urothelial Cancer (UC) Failing First-line Treatment.

Salvage chemotherapy for advanced urothelial cancer (UC) yields suboptimal response rates of 15-40%, a median progression-free survival of 2-4 months and a median overall survival of 6 months. A rationale for targeting angiogenesis in UC is supported by preclinical evidences and early signals of clinical activity of anti-VEGF TKI as demonstrated by our group with the use of pazopanib.

Despite this activity, progression inevitably occurs and mechanisms determining resistance to conventional anti-angiogenic agents are under investigation.

PF-03446962 (Pfizer Inc) is a novel fully human monoclonal antibody (mAb) against ALK1 with dose-dependent antiangiogenic activity as demonstrated in nonclinical studies in a chimera mouse model bearing human tumor xenograft. The investigators suggest that PF-03446962 may increase current results for patients with advanced urothelial cancer failing upfront chemotherapy due to its mechanisms of action. Due to the lack of reliable and reproducible predictors of response as well as of imaging tools to assess tumor response, the trial will provide incorporation of 18FDG-PET/CT and contrast-enhanced ultrasound to stage and evaluate response of urothelial cancers, together with standard imaging modalities (RECIST criteria). Blood and tissue samples will be collected for translational purposes.

Read the detailed description

This is an open-label, single arm, non randomised, phase II proof-of-concept study of the monoclonal antibody against TGF-beta receptor ALK1 (PF03446962) for patients with urothelial cancer relapsing/progressing after first line chemotherapy.

The study is planned according to Simon's Optimal two-stage design. The primary endpoint is the proportion of patients who are progression-free at 2-months. A 2-month PFS rate of 50% is not promising, while a 70% rate will be promising. In stage 1, 21 evaluable patients will be accrued. If 12 patients at least will be progression-free at 2 months, enrollment will be extended to the 2nd stage for further 24 patients. If, out of the total of 45 patients, 27 at least will be progression-free at 2 months, treatment will be declared worthy for further investigations.

Maximum overall accrual is 45 patients. Type I and type II error rates will be set both at the 10% level.

Being tested
PF03446962
Keywords
Transitional Cell Carcinoma, Metastatic disease, Bladder tumors, Recurrent, Angiogenesis, PF03446962, Transforming growth factor beta, Activin receptor like kinase 1, Monoclonal Antibody, Locally advanced or metastatic disease, Failure of one platinum-based chemotherapy, Measurable disease
Medical subject headings
Carcinoma, Transitional Cell, Neoplasm Metastasis, Urinary Bladder Neoplasms, Recurrence, Camurati-Engelmann Syndrome

What participants receive

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

  • PF03446962Drug

    PF-03446962 will be administered in 1hr intravenously at a dose of 10 mg/Kg on day 1, then every 2 weeks until the evidence of disease progression or onset of unacceptable toxicity.

Study groups in NCT01620970
Study groupRoleWhat they receive
PF03446962ExperimentalInvestigational study drug, administered intravenously every 2 weeks until disease progression or unacceptable toxicity.
Receives: Drug: PF03446962

What is being measured

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

  1. Progression-free survival.

    Progression-free survival (PFS) is defined as the interval from the first dose of study drug to the date of the first documented disease progression or death for any reason, with censoring at the date of last contact for alive patients. A patient who has not progressed or died by the date of the analysis cut-off or when the patient received any further anticancer therapy would have the PFS censored at the time of last adequate tumor assessment before either cut-off date or the commencement of further anticancer therapy date, respectively.

    Measured: 2-month

Secondary outcomes (4)

  1. Safety (CTCAE v.4.03)

    Incidence of adverse events (AEs), defined as any new untoward medical conditions occurrence or worsening of a pre-existing medical condition that does not necessarily have a causal relationship with the study drugs. AEs will be graded according to the NCI-CTC version 4.03 and the relationship of each AEs to study drugs will be assessed by the investigator.

    Measured: 2-month

  2. RECIST response-rate

    Assessment of response-rate by RECIST v1.1 criteria. RR (%) = CR + PR

    Measured: 2-month

  3. Overall Survival

    Overall Survival (OS) will be calculated as the interval from the date of the first dose of study drug to the date of death for any cause, with censoring at the date of last contact for patients alive. The Kaplan-Meier method will be used to estimate the OS curve (median and 95% confidence interval).

    Measured: 6-month

  4. Circulating and Tissue Biomarkers

    Tissue will be examined in terms of genotyping by high-resolution array comparative genome hybridization (aCGH) and expression of VEGFR, PDGFR, KIT, EGFR, HER2/neu, PTEN on tissue microarrays (TMAs).

    Circulating VEGF, soluble VEGFR-1, 2 and -3, soluble c-Kit, IL-6, 8, 12 and HGF will be evaluated by using multiplex ELISA plates.

    Circulating tumor cells will be evaluated as a potential response biomarkers.

    Measured: Baseline and 2 months

Timeline

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

  1. First posted15 Jun 2012 (estimated)
  2. Study start1 Mar 2012
  3. Primary completion1 Jun 2013
  4. Study completion1 Jun 2013

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01620970
Sponsor's protocol ID
INT01/12
Other IDs
2011-005983-12
Status last verified
May 2021
First submitted
11 Jun 2012
Last updated
14 May 2021
Results posted
No
Data monitoring committee
Yes

Publications

  • Hu-Lowe DD, Chen E, Zhang L, Watson KD, Mancuso P, Lappin P, Wickman G, Chen JH, Wang J, Jiang X, Amundson K, Simon R, Erbersdobler A, Bergqvist S, Feng Z, Swanson TA, Simmons BH, Lippincott J, Casperson GF, Levin WJ, Stampino CG, Shalinsky DR, Ferrara KW, Fiedler W, Bertolini F. Targeting activin receptor-like kinase 1 inhibits angiogenesis and tumorigenesis through a mechanism of action complementary to anti-VEGF therapies. Cancer Res. 2011 Feb 15;71(4):1362-73. doi: 10.1158/0008-5472.CAN-10-1451. Epub 2011 Jan 6.

    PubMed 21212415

  • Necchi A, Giannatempo P, Mariani L, Fare E, Raggi D, Pennati M, Zaffaroni N, Crippa F, Marchiano A, Nicolai N, Maffezzini M, Togliardi E, Daidone MG, Gianni AM, Salvioni R, De Braud F. PF-03446962, a fully-human monoclonal antibody against transforming growth-factor beta (TGFbeta) receptor ALK1, in pre-treated patients with urothelial cancer: an open label, single-group, phase 2 trial. Invest New Drugs. 2014 Jun;32(3):555-60. doi: 10.1007/s10637-014-0074-9. Epub 2014 Feb 26.

    PubMed 24566706

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PF03446962 in people with Transitional Cell Carcinoma of Bladder, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.

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 9 inclusion and 6 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: finished, as of the sponsor's last update on 14 May 2021. 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 Italy. 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 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Progression-free survival. (time frame: 2-month). 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 NCT01620970, which also lists 2 linked publications.

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 14 May 2021.

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