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

Ovarian Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01881451
• Other study ID #: H13-00921
• Status: Terminated
• Start date: August 2013
• Est. completion date: May 2020

Study information

• Verified date: December 2018
• Source: British Columbia Cancer Agency
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: May 2020
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Hypoxia
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

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

Procedure:
• Optional biopsy
Patients who choose to participate, will undergo a tissue biopsy.

Locations

Country	Name	City	State
Canada	BC Cancer Agency - Vancouver Centre	Vancouver	British Columbia

Sponsors (2)

Lead Sponsor	Collaborator
British Columbia Cancer Agency	Carraressi Foundation OVCARE

Country where clinical trial is conducted

Canada, 

References & Publications (18)

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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. — View Citation

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. — View Citation

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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. — View Citation

Komar G, Seppänen M, Eskola O, Lindholm P, Grönroos TJ, Forsback S, Sipilä 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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Baseline