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Ovarian CancerNCT01881451

Imaging Tumor Hypoxia With 18F-EF5 PET in Recurrent or Metastatic Clear Cell Ovarian Cancer

An observational study of Ovarian Cancer and Ovarian Neoplasms, run by British Columbia Cancer Agency at 1 site in Canada.

Terminated

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

Official record
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Trial summary

The purpose of this study is to use 18F-EF5 PET/CT scans to locate areas with low oxygen levels (hypoxia) in patients with recurrent and/or metastatic cancer. Read more about this study

Who is it for?
Ages 19 years and older
Conditions the study is for
Ovarian Cancer, Ovarian Neoplasms
What is being tested?
18F-EF5 PET/CT scan and Optional biopsy
Type of treatment
Surgery or procedure
How many people
5 participants
Where
1 siteCanada
Study dates
Aug 2013to May 2020
Phase
Observational
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 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Eligible participants with recurrent or metastatic clear cell ovarian cancer will be approached for study participation at the time of their visit with their treating oncologist (medical oncologist, radiation oncologist or gynecologic oncologist).

Who may be able to join

  • Histologically confirmed, advanced metastatic or recurrent clear cell cancer of the ovary
  • At least one index lesion measuring 2 cm in diameter
  • Must be able to provide written informed consent, and willing to comply with protocol procedures of the study
  • Off all active therapy for at least 4 weeks (cytotoxic chemotherapy, radiation, immune therapy, hormone therapy, clinical trials or new agents)

Who cannot join

  • Renal failure (eGFR < 50mls/min)
  • Patients with unknown primaries
  • Previous history of cancer, except treated non-melanoma skin cancer, non-invasive breast cancer, non-invasive cervical cancer; or curatively treated solid cancer with no evidence of recurrence for more than 5 years.
  • Receiving or had received active therapy in the form or chemotherapy or radiation within 4 weeks of the PET scan
  • ECOG status ≥ 3
  • Unable to tolerate a PET scan which involves an injection of radiopharmaceutical and lying flat and still for 30 minutes.
  • Weight more than 204.5 kg (Physical Limitation of Imaging and Radiotherapy Couches) or cannot fit through the PET/CT machine (diameter 70cm).
  • Patient is pregnant or breastfeeding

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • BC Cancer Agency - Vancouver Centre

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

About this study

The purpose of this study is to use 18F-EF5 PET/CT scans to locate areas with low oxygen levels (hypoxia) in patients with recurrent and/or metastatic cancer.

Read the detailed description

This study involves one visit to the BCCA - Vancouver Centre to undergo one EF5-PET/CT scan. The visit will take about 4 hours to complete and no follow-up visits are required.

  • Participants will fill out a short medical questionnaire asking routine information (treatment history, previous surgeries, medications, allergies, etc.) that will take about 5-10 minutes to complete.
  • Next they will be weighed and vital signs measured (blood pressure, heart rate and blood oxygen saturation).
  • An IV is inserted into a vein in the participant's arm. At the same, a small amount of blood will be taken to measure their blood glucose level.
  • The participant will receive an IV dose of 18F-EF5.
  • Five minutes after the injection, blood pressure and heart rate will be checked again.
  • Participants will then be free to leave the functional imaging department for a period of 180 minutes while the 18F-EF5 circulates throughout their body. Participants are free to eat as normal during this period.
  • Participants will undergo the 18F-EF5 PET scan, which will take about 20 minutes. The participant will need to lie still on the scanner bed during the entire scan.
  • The 18F-EF5 PET scan will be reviewed by a BC Cancer Agency doctor specialized in PET and the results will be sent to their referring doctor.

Optional Biopsy Procedure:

Participants will have the opportunity of participating in an optional biopsy procedure for the purposes of further studying contemporaneous tumour tissue (contemporaneous with the EF5-PET) for markers of hypoxia, apoptosis, angiogenesis etc. The tissue will also be compared to archival material, and this will allow researchers to study the evolving changes in tumours following treatment.

Patients who consent to undergo a biopsy will be booked to the Diagnostic Imaging Department at the Vancouver Centre. Ultrasound guidance will be used to obtain up to 5 core biopsies from an accessible lesion(s). Up to 2 distinct tumour areas may be sampled. The standard procedure required for a core biopsy will be followed, which will include pre-biopsy lab tests, sterile technique, and when needed, post biopsy observation.

The core biopsies will be formalin fixed and paraffin embedded (FFPE). A BCCA pathologist will review representative slides of each paraffin block to ensure the presence of tumour tissue. The FFPE block will then be sent to the laboratory for immunohistochemistry staining and further interpretation.

Being tested
18F-EF5 PET/CT scan, Optional biopsy
Keywords
Tumour hypoxia, Clear Cell Ovarian Cancer, Recurrent, Metastatic
Medical subject headings
Ovarian Neoplasms, Recurrence, Neoplasm Metastasis

What participants receive

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

  • 18F-EF5 PET/CT scanDrug

    Patients will undergo an investigations 18F-EF5 PET/CT scan.

  • Optional biopsyProcedure or surgery

    Patients who choose to participate, will undergo a tissue biopsy.

What is being measured

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

  1. Ability of 18F-EF5 to detect areas of tumour hypoxia in clear cell tumours of the ovary

    18F-EF5 uptake will be evaluated semi-quantitatively by determining the tumor-to-muscle activity ratio (T/M). Standardized uptake values (SUV) will be calculated for suspicious areas using a region of interest drawn around the target area on the PET images where SUV = (peak activity/mL in region of interest) / (injected activity/g of body weight). A Tumor-to-muscle ratio of >1.5 is considered positive.

    Measured: Baseline

Secondary outcomes (1)

  1. Correlate cellular markers of hypoxia and autophagy to the results of the 18F-EF5 PET/CT scans.

    Archival tumour tissue will be obtained with consent when possible/available. New biopsies will be obtained as part of the optional consent process, when safe. Archival and new tumour tissue will be assessed using multi-parameter staining for LC3A/B (autophagy), EF5 (hypoxia) and cleaved caspase 3 (apoptosis). Whenever tumour availability is not limited, we will comprehensively assess gene expression involved in hypoxia, angiogenesis, autophagy, apoptosis, and chemotherapy resistance.

    Measured: Baseline

Timeline

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

  1. First posted19 Jun 2013 (estimated)
  2. Study startAug 2013
  3. Primary completionMar 2016
  4. Study completionMay 2020

Why it stopped: Due to slow accrual and access to the study drug.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case only
Time perspective
Prospective
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01881451
Sponsor's protocol ID
H13-00921
Status last verified
Dec 2018
First submitted
14 Jun 2013
Last updated
17 Feb 2022
Results posted
No
Data monitoring committee
No

Publications

  • GRAY LH, CONGER AD, EBERT M, HORNSEY S, SCOTT OC. The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radiol. 1953 Dec;26(312):638-48. doi: 10.1259/0007-1285-26-312-638. No abstract available.

    PubMed 13106296

  • Fyles AW, Milosevic M, Wong R, Kavanagh MC, Pintilie M, Sun A, Chapman W, Levin W, Manchul L, Keane TJ, Hill RP. Oxygenation predicts radiation response and survival in patients with cervix cancer. Radiother Oncol. 1998 Aug;48(2):149-56. doi: 10.1016/s0167-8140(98)00044-9.

    PubMed 9783886

  • Hockel M, Schlenger K, Knoop C, Vaupel P. Oxygenation of carcinomas of the uterine cervix: evaluation by computerized O2 tension measurements. Cancer Res. 1991 Nov 15;51(22):6098-102.

    PubMed 1933873

  • Evans SM, Hahn SM, Magarelli DP, Zhang PJ, Jenkins WT, Fraker DL, Hsi RA, McKenna WG, Koch CJ. Hypoxia in human intraperitoneal and extremity sarcomas. Int J Radiat Oncol Biol Phys. 2001 Feb 1;49(2):587-96. doi: 10.1016/s0360-3016(00)01494-2.

    PubMed 11173159

  • Nordsmark M, Loncaster J, Aquino-Parsons C, Chou SC, Ladekarl M, Havsteen H, Lindegaard JC, Davidson SE, Varia M, West C, Hunter R, Overgaard J, Raleigh JA. Measurements of hypoxia using pimonidazole and polarographic oxygen-sensitive electrodes in human cervix carcinomas. Radiother Oncol. 2003 Apr;67(1):35-44. doi: 10.1016/s0167-8140(03)00010-0.

    PubMed 12758238

  • Koch CJ, Scheuermann JS, Divgi C, Judy KD, Kachur AV, Freifelder R, Reddin JS, Karp J, Stubbs JB, Hahn SM, Driesbaugh J, Smith D, Prendergast S, Evans SM. Biodistribution and dosimetry of (18)F-EF5 in cancer patients with preliminary comparison of (18)F-EF5 uptake versus EF5 binding in human glioblastoma. Eur J Nucl Med Mol Imaging. 2010 Nov;37(11):2048-59. doi: 10.1007/s00259-010-1517-y. Epub 2010 Jun 29.

    PubMed 20585774

  • Evans SM, Fraker D, Hahn SM, Gleason K, Jenkins WT, Jenkins K, Hwang WT, Zhang P, Mick R, Koch CJ. EF5 binding and clinical outcome in human soft tissue sarcomas. Int J Radiat Oncol Biol Phys. 2006 Mar 1;64(3):922-7. doi: 10.1016/j.ijrobp.2005.05.068.

    PubMed 16458778

  • Evans SM, Judy KD, Dunphy I, Jenkins WT, Hwang WT, Nelson PT, Lustig RA, Jenkins K, Magarelli DP, Hahn SM, Collins RA, Grady MS, Koch CJ. Hypoxia is important in the biology and aggression of human glial brain tumors. Clin Cancer Res. 2004 Dec 15;10(24):8177-84. doi: 10.1158/1078-0432.CCR-04-1081.

    PubMed 15623592

  • Yapp DT, Woo J, Kartono A, Sy J, Oliver T, Skov KA, Koch CJ, Adomat H, Dragowska WH, Fazli L, Ruth T, Adam MJ, Green D, Gleave M. Non-invasive evaluation of tumour hypoxia in the Shionogi tumour model for prostate cancer with 18F-EF5 and positron emission tomography. BJU Int. 2007 May;99(5):1154-60. doi: 10.1111/j.1464-410X.2007.06761.x. Epub 2007 Feb 19.

    PubMed 17309552

  • Komar G, Seppanen M, Eskola O, Lindholm P, Gronroos TJ, Forsback S, Sipila H, Evans SM, Solin O, Minn H. 18F-EF5: a new PET tracer for imaging hypoxia in head and neck cancer. J Nucl Med. 2008 Dec;49(12):1944-51. doi: 10.2967/jnumed.108.053785. Epub 2008 Nov 7.

    PubMed 18997048

  • Mackay HJ, Brady MF, Oza AM, Reuss A, Pujade-Lauraine E, Swart AM, Siddiqui N, Colombo N, Bookman MA, Pfisterer J, du Bois A; Gynecologic Cancer InterGroup. Prognostic relevance of uncommon ovarian histology in women with stage III/IV epithelial ovarian cancer. Int J Gynecol Cancer. 2010 Aug;20(6):945-52. doi: 10.1111/IGC.0b013e3181dd0110.

    PubMed 20683400

  • Spowart JE, Townsend KN, Huwait H, Eshragh S, West NR, Ries JN, Kalloger S, Anglesio M, Gorski SM, Watson PH, Gilks CB, Huntsman DG, Lum JJ. The autophagy protein LC3A correlates with hypoxia and is a prognostic marker of patient survival in clear cell ovarian cancer. J Pathol. 2012 Dec;228(4):437-47. doi: 10.1002/path.4090.

    PubMed 22926683

  • Yamaguchi K, Mandai M, Oura T, Matsumura N, Hamanishi J, Baba T, Matsui S, Murphy SK, Konishi I. Identification of an ovarian clear cell carcinoma gene signature that reflects inherent disease biology and the carcinogenic processes. Oncogene. 2010 Mar 25;29(12):1741-52. doi: 10.1038/onc.2009.470. Epub 2010 Jan 11.

    PubMed 20062075

  • Anglesio MS, George J, Kulbe H, Friedlander M, Rischin D, Lemech C, Power J, Coward J, Cowin PA, House CM, Chakravarty P, Gorringe KL, Campbell IG; Australian Ovarian Cancer Study Group; Okamoto A, Birrer MJ, Huntsman DG, de Fazio A, Kalloger SE, Balkwill F, Gilks CB, Bowtell DD. IL6-STAT3-HIF signaling and therapeutic response to the angiogenesis inhibitor sunitinib in ovarian clear cell cancer. Clin Cancer Res. 2011 Apr 15;17(8):2538-48. doi: 10.1158/1078-0432.CCR-10-3314. Epub 2011 Feb 22.

    PubMed 21343371

  • Stany MP, Vathipadiekal V, Ozbun L, Stone RL, Mok SC, Xue H, Kagami T, Wang Y, McAlpine JN, Bowtell D, Gout PW, Miller DM, Gilks CB, Huntsman DG, Ellard SL, Wang YZ, Vivas-Mejia P, Lopez-Berestein G, Sood AK, Birrer MJ. Identification of novel therapeutic targets in microdissected clear cell ovarian cancers. PLoS One. 2011;6(7):e21121. doi: 10.1371/journal.pone.0021121. Epub 2011 Jul 6.

    PubMed 21754983

Questions about this trial

What is this clinical trial studying?

An observational study of Ovarian Cancer and Ovarian Neoplasms, run by British Columbia Cancer Agency at 1 site in Canada.

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 4 inclusion and 8 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 17 Feb 2022. 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 Canada. 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.

Are results available for this study?

The study was stopped early (reason given: Due to slow accrual and access to the study drug.). 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?

Ability of 18F-EF5 to detect areas of tumour hypoxia in clear cell tumours of the ovary (time frame: Baseline). 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 NCT01881451, which also lists 18 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 17 Feb 2022.

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