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

NCT01881451 | Terminated

• 1 other identifier: H13-00921
• Study Type: observational
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Ovarian Cancer; Ovarian Neoplasms

Keywords

Tumour hypoxia; Clear Cell Ovarian Cancer; Recurrent; Metastatic

Outcome Measures

Primary Outcomes (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.

  Baseline

Secondary Outcomes (1)

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

  Baseline

Interventions

18F-EF5 PET/CT scan DRUG

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

Optional biopsy PROCEDURE

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

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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).

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• British Columbia Cancer Agency: lead
• Carraressi Foundation OVCARE: collaborator

Study Sites (1)

BC Cancer Agency - Vancouver Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Related Publications (18)

• 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.

  PMID: 13106296 BACKGROUND

• 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.

  PMID: 9783886 BACKGROUND

• 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.

  PMID: 1933873 BACKGROUND

• 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.

  PMID: 11173159 BACKGROUND

• 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.

  PMID: 12758238 BACKGROUND

• 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.

  PMID: 20585774 BACKGROUND

• 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.

  PMID: 16458778 BACKGROUND

• 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.

  PMID: 15623592 BACKGROUND

• 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.

  PMID: 17309552 BACKGROUND

• 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.

  PMID: 18997048 BACKGROUND

• 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.

  PMID: 20683400 BACKGROUND

• 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.

  PMID: 22926683 BACKGROUND

• 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.

  PMID: 20062075 BACKGROUND

• 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.

  PMID: 21343371 BACKGROUND

• 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.

  PMID: 21754983 BACKGROUND

• Cheong H, Lu C, Lindsten T, Thompson CB. Therapeutic targets in cancer cell metabolism and autophagy. Nat Biotechnol. 2012 Jul 10;30(7):671-8. doi: 10.1038/nbt.2285.

  PMID: 22781696 BACKGROUND

• Amaravadi RK, Yu D, Lum JJ, Bui T, Christophorou MA, Evan GI, Thomas-Tikhonenko A, Thompson CB. Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma. J Clin Invest. 2007 Feb;117(2):326-36. doi: 10.1172/JCI28833. Epub 2007 Jan 18.

  PMID: 17235397 BACKGROUND

• Hu YL, DeLay M, Jahangiri A, Molinaro AM, Rose SD, Carbonell WS, Aghi MK. Hypoxia-induced autophagy promotes tumor cell survival and adaptation to antiangiogenic treatment in glioblastoma. Cancer Res. 2012 Apr 1;72(7):1773-83. doi: 10.1158/0008-5472.CAN-11-3831. Epub 2012 Mar 23.

  PMID: 22447568 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

The collection of archival tumour blocks from the time of prior surgery/biopsy and any newly obtained biopsies (newly obtained biopsies are optional) will be used to construct a tumour tissue microarray (TMA). The TMA will be assessed using multi-parameter staining for LC3A/B (autophagy), EF5 (hypoxia) and cleaved caspase 3 (apoptosis).

MeSH Terms

Conditions

Ovarian Neoplasms; Recurrence; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Study Officials

• Anna Tinker, MD, FRCPC

  British Columbia Cancer Agency

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2013
• First Posted: June 19, 2013
• Study Start: August 1, 2013
• Primary Completion: March 1, 2016
• Study Completion: May 1, 2020
• Last Updated: February 17, 2022

Record last verified: 2018-12

Locations

CA (1)