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Advanced Cervical CancerPhase 1/2NCT01088347

Mapatumumab, Cisplatin and Radiotherapy for Advanced Cervical Cancer

A Phase 1/2 study testing mapatumumab, cisplatin and radiotherapy in people with Advanced Cervical Cancer, run by University Medical Center Groningen at 1 site in Netherlands.

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

Chemoradiotherapy has become the standard of care for women with locally advanced cervical cancer. The available data support a 30 to 50% reduction in the risk of death from cervical cancer for women with locally advanced disease undergoing radiotherapy (RT) and concomitant cisplatin-based chemotherapy compared to RT… Read more about this study

Who is it for?
Ages 18 to 99 years, women only
Conditions the study is for
Advanced Cervical Cancer
What is being tested?
mapatumumab, cisplatin and radiotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteNetherlands
Study dates
Mar 2010to Mar 2014
Phase
Phase 1/2
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 to 99 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with histologically or cytologically confirmed stage IB2, IIA2, IIB, III, and IVA cervical cancer, according to the FIGO classification
  • Adequate bone marrow, renal and liver function:
  • Absolute neutrophil count ≥ 1.5 x 109 /L.
  • Platelet count ≥ 100 x 109 /L.
  • Serum creatinine level ≤ 1.5 x upper limit of normal (ULN).
  • Total bilirubin < 1.25 x ULN.
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  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN.
  • Performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) Scale.
  • Age 18 years or older.
  • Life expectancy of ≥ 12 weeks.
  • Have the ability to understand the requirements of the study, provide written informed consent (including consent for the use and disclosure of research-related health information), and comply with the study and follow-up procedures.

Who cannot join

  • Any co-morbid condition that in the judgment of the investigator renders the subject at high risk of treatment complications or reduces the possibility of assessing clinical effect.
  • Cytotoxic agent, hormonal therapy, or radiation therapy within 3 weeks (6 weeks for nitrosoureas or mitomycin-C) prior to day 1, cycle 1; investigational agent within 4 weeks prior to day 1, cycle 1.
  • Need for concomitant anticancer therapy (surgery, radiation therapy, chemotherapy, immunotherapy, radiofrequency ablation) or other investigational agents during the study treatment period.
  • Major surgery within 4 weeks before enrollment; minor surgery (except for insertion of vascular access device) within 2 weeks before enrollment; or not yet recovered from the effects of the surgery.
  • Systemic steroids within 1 week before enrollment except steroids used as part of an antiemetic regimen or maintenance-dose steroids for non-cancerous disease.
  • History of any infection requiring hospitalization or antibiotics within 2 weeks before enrollment.
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  • Known brain or spinal cord metastases unless adequately treated (surgery or radiotherapy) with no evidence of progression and neurologically stable off anticonvulsants and steroids.
  • Known human immunodeficiency virus infection.
  • Unstable angina, myocardial infarction, cerebrovascular accident, > Class II congestive heart failure according to the New York Heart Association Classification for Congestive Heart Failure within 6 months before enrollment.
  • Pregnant female or nursing mother.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • University Medical Center Groningen

    Groningen, 9700 RB

Other trials in Netherlands

About this study

Official title: A Phase 1b/2 Study With the Agonistic TRAIL-R1 Antibody, Mapatumumab, in Combination With Cisplatin and Radiotherapy as a First Line Therapy in Patients With Advanced Cervical Cancer.

Chemoradiotherapy has become the standard of care for women with locally advanced cervical cancer. The available data support a 30 to 50% reduction in the risk of death from cervical cancer for women with locally advanced disease undergoing radiotherapy (RT) and concomitant cisplatin-based chemotherapy compared to RT alone. Despite the fact that this is currently the best treatment of locally advanced cervical cancer, 5-year overall survival is still only 52%.

The fully human, agonist monoclonal antibody mapatumumab binds to the Tumor necrosis factor-Related Apoptosis-Inducing Ligand Receptor 1 (TRAIL-R1, DR4) and induces cytotoxicity in multiple tumor cell lines in vitro and in vivo. In multiple phase I and phase II studies, mapatumumab appeared to be safe both as single agent and in combination with chemotherapy, including cisplatin.

Read more

In cervical cancer cell lines, mapatumumab induced apoptosis in 51% of the cells. Mapatumumab in combination with irradiation increased apoptosis to 83%.

In this phase 1b/2 study, the investigators will evaluate the safety, tolerability and efficacy of mapatumumab in combination with cisplatin and radiotherapy in patients with locally advanced cervical cancer.

Being tested
mapatumumab, cisplatin, radiotherapy
Keywords
TRAIL, TRM1, advanced cervical cancer, mapatumumab, Uterine cervical neoplasm, Radiotherapy, Cisplatin
Medical subject headings
Uterine Cervical Neoplasms

What participants receive

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

  • mapatumumabDrug

    Mapatumumab (10 or 30 mg/kg) intravenously on days 1, 22, and 45. In phase 2 the MTD established in phase 1 will be used.

  • cisplatinDrug

    Cisplatin 40 mg/m2 intravenously on days 8, 15, 22, 29, 36, and 45

  • radiotherapyRadiation

    Radiotherapy: a total dose of 45 Gy will be given in fractions of 1.8 Gy, five fractions per week (days 8-12, 15-19, 22-26, 29-33, and 36-40), by external beam irradiation by photon beam of at least 6 MV. After completing the five weeks of external beam irradiation, evaluation will take place to determine whether the boost can be given by brachytherapy. If brachytherapy is not feasible, the boost will be given by external beam irradiation to a total dose of 70.2 Gy in fractions of 1.8 Gy.

Study groups in NCT01088347
Study groupRoleWhat they receive
Advanced cervical cancer patientsExperimentalNot described
Receives: Drug: mapatumumab; Drug: cisplatin; Radiation: radiotherapy

What is being measured

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

  1. Phase 1b: safety and tolerability of mapatumumab in combination with cisplatin and radiotherapy Phase 2: efficacy of mapatumumab in combination with cisplatin and radiotherapy

    Phase 2: pathological complete response rate

    Measured: 5 months

Secondary outcomes (2)

  1. Disease free survival, overall survival

    Measured: From enrollment until recurrence of disease, from enrollment until death

  2. Apoptotic pathway biomarkers, PK parameters

    Measured: During the study, until 5 months after enrollment

Timeline

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

  1. First posted17 Mar 2010 (estimated)
  2. Study startMar 2010
  3. Primary completionMar 2014
  4. Study completionMar 2014

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01088347
Sponsor's protocol ID
24-11-2009 (versions 2.0)
Other IDs
2009-015941-22, 2009
Status last verified
Apr 2024
First submitted
10 Mar 2010
Last updated
19 Apr 2024
Results posted
No
Data monitoring committee
Yes

Publications

  • Maduro JH, de Vries EG, Meersma GJ, Hougardy BM, van der Zee AG, de Jong S. Targeting pro-apoptotic trail receptors sensitizes HeLa cervical cancer cells to irradiation-induced apoptosis. Int J Radiat Oncol Biol Phys. 2008 Oct 1;72(2):543-52. doi: 10.1016/j.ijrobp.2008.06.1902.

    PubMed 18793956

  • Mom CH, Verweij J, Oldenhuis CN, Gietema JA, Fox NL, Miceli R, Eskens FA, Loos WJ, de Vries EG, Sleijfer S. Mapatumumab, a fully human agonistic monoclonal antibody that targets TRAIL-R1, in combination with gemcitabine and cisplatin: a phase I study. Clin Cancer Res. 2009 Sep 1;15(17):5584-90. doi: 10.1158/1078-0432.CCR-09-0996. Epub 2009 Aug 18.

    PubMed 19690193

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing mapatumumab, cisplatin and radiotherapy in people with Advanced Cervical Cancer, run by University Medical Center Groningen at 1 site in Netherlands.

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 11 inclusion and 10 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 19 Apr 2024. 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 Netherlands. 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?

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?

Phase 1b: safety and tolerability of mapatumumab in combination with cisplatin and radiotherapy Phase 2: efficacy of mapatumumab in combination with cisplatin and radiotherapy (time frame: 5 months). 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 NCT01088347, 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 19 Apr 2024.

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