No Surgery Trial / Two Dose-escalation Strategies (Morpheus)

Sir Mortimer B. Davis - Jewish General Hospital

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Stage II Rectal Cancer

Treatments: Radiation: Chemoradiation + HDRBT Boost; Radiation: Chemoradiation + EBRT Boost; Procedure: Complete responders and Non-complete responders

Study type: Interventional

Funder types: Other

Identifiers

NCT03051464

16-301

Details and patient eligibility

About

A randomized study of 131 patients. Patients with a clinical T2-3 N0 rectal cancer will be randomized to two arms (arm A: standard chemoradiation (45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and an external beam boost of 9 Gy compared to arm B: standard chemoradiation (45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and followed by a brachytherapy boost of 30 Gy in 3 fractions).

Full description

It is becoming clear that there is a now an international consensus that rectal cancer research efforts need to be more focused in optimizing a non-surgical approach. This concept is very relevant to an ageing patient population with multiple co-morbidities regularly seen at the Jewish General Hospital and across the province. After interim analysis on 40 patients of the pilot study a phase III study is proposed. We are therefore proposing a phase III multicentric study of 145 patients to compare the two best known radiation dose escalation strategies and to achieve a complete clinical response. Patients with a clinical T2-3 N0-1 rectal cancer will be randomized to two arms (arm A: standard chemoradiation (45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and an external beam boost of 9 Gy compared to arm B: standard chemoradiation (45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and followed by a brachytherapy boost of 30 Gy in 3 fractions). Patients that have a high risk of recurrence or with more advanced stages of the disease will be excluded from the study, as only the local disease is being treated. The primary outcome for this proposal is rectum preservation in treated patients.

Enrollment: 131 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Rectal cancer patients, clinically staged as T2-T3 by MRI or endoscopic/trans-rectal ultrasound
• Rectal cancer staged as N0 by MRI or EUS/TRUS
• No metastatic lesion
• Rectal tumor occupying less than half of the circumference
• Tumor less than 5 cm on its largest dimension
• Tumor located at less than 10 cm from the anal verge
• Tumor penetration less than 5 mm in the mesorectal fat
• Tumor accessible for brachytherapy
• Lumen accessible for colonoscopy
• Patient should be a suitable candidate for brachytherapy and chemotherapy
• Older than 18 years of age
• Adequate birth control measures in women of childbearing potential
• Written informed consent

Exclusion criteria

• Patients with previous pelvic radiation
• Evidence of distant metastasis
• Extension of malignant disease to the anal canal
• Tumors staged as T4
• Tumors larger than 5 cm in length

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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131 participants in 2 patient groups

Chemoradiation + EBRT Boost

Experimental group

Description:

standard chemoradiation (45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and an external beam boost of 9 Gy in 5; Complete responders and Non-complete responders

Treatment:

Procedure: Complete responders and Non-complete responders

Radiation: Chemoradiation + EBRT Boost

Chemoradiation + HDRBT Boost

Experimental group

Description:

standard chemoradiation (45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and followed by a brachytherapy boost of 30 Gy in 3 fractions; Complete responders and Non-complete responders

Treatment:

Procedure: Complete responders and Non-complete responders

Radiation: Chemoradiation + HDRBT Boost