Trial Outcomes & Findings for An Observational Study of Xeloda (Capecitabine) and Oxaliplatin Prior and Concurrent To Preoperative Pelvic Radiotherapy in Patients With Locally Advanced Rectal Cancer (NCT NCT01339832)

Last Updated: 2017-05-17

Results Overview

Progression free survival (PFS) was measured from the date of first administration of study medication in ML18280 study to the date of progression or death, whatever the cause. In participants with measurable disease, progression was defined according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.0. Participants with neither tumor recurrence nor death were censored at the last tumor assessment date they were known to have not progressed (last date of diagnostic procedure or diagnostic marker reported in the surveillance). PFS time in days was calculated as PFS \[days\]= date of tumor recurrence/death date of first intake + 1, if participant had tumor recurrence confirmed by diagnostic imaging or participant died, then PFS \[days\] =last diagnostic procedure/marker date- date of first intake+ 1, and if participant survived without tumor recurrence PFS time in months was calculated as PFS \[months\]= 12 \* PFS \[days\] /365.25

Recruitment status

COMPLETED

Target enrollment

51 participants

Primary outcome timeframe

Up to 5 years

Results posted on

2017-05-17

Participant Flow

All participants who were treated in ML18280 base study were followed-up two, three, four years and if necessary five years after the last surgery in Switzerland (5 centers) and data concerning to the adjuvant therapy, surveillance visit, tumor recurrence or second carcinoma and survival status were collected.

Of the 56 participants in the ML18280 base study, 51 were included in ML21875 study. Retrospective data was documented for 14 participants and prospective data was obtained for 37 participants.

Participant milestones

Participant milestones
Measure	Overall Participants with histologically proven local advanced T3/T4 rectal carcinoma with or without nodal involvement who had participated in study ML18280 were enrolled and no active treatment was given during this study
Overall Study STARTED	51
Overall Study COMPLETED	37
Overall Study NOT COMPLETED	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Overall Participants with histologically proven local advanced T3/T4 rectal carcinoma with or without nodal involvement who had participated in study ML18280 were enrolled and no active treatment was given during this study
Overall Study Lost to Follow-up	3
Overall Study Death	11

Baseline Characteristics

An Observational Study of Xeloda (Capecitabine) and Oxaliplatin Prior and Concurrent To Preoperative Pelvic Radiotherapy in Patients With Locally Advanced Rectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Overall n=51 Participants Participants with histologically proven local advanced T3/T4 rectal carcinoma with or without nodal involvement who had participated in study ML18280 were enrolled and no active treatment was given during this study
Age, Continuous	59.8 years STANDARD_DEVIATION 8.8 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	40 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 5 years

Population: Full Analysis Set (FAS) included all the participants who fulfilled the inclusion criteria for this study. This population includes participants who gave informed consent and also those who died or were lost to follow-up before start of ML21875 study.

Outcome measures

Outcome measures
Measure	Overall n=51 Participants Participants with histologically proven local advanced T3/T4 rectal carcinoma with or without nodal involvement who had participated in study ML18280 were enrolled and no active treatment was given during this study
Progression-free Survival	15.4 months Interval 7.3 to 60.0

SECONDARY outcome

Timeframe: Up to 5 years

Overall survival (OS) was defined as time from date of first administration of the study medication in ML18280 study to date of death from any cause. Participants without documented date of death were assumed to be alive and were censored at the latest of the following dates: last date alive on survival status pages, last date known to be alive on survival status pages, and last date of tumor assessment (diagnostic procedures or markers) on surveillance pages. OS time in days was calculated as OS \[days\] =date of death date of first intake+ 1, for participants who died, OS \[days\]= censoring date date of first intake+ 1, for participants alive, and OS time in months was calculated as OS \[months\]= 12 \*OS \[days\] /365.25

Outcome measures

Outcome measures
Measure	Overall n=51 Participants Participants with histologically proven local advanced T3/T4 rectal carcinoma with or without nodal involvement who had participated in study ML18280 were enrolled and no active treatment was given during this study
Overall Survival	22.51 months Interval 10.3 to 60.0

SECONDARY outcome

Timeframe: Up to 5 years

Participant with tumor recurrence were determined by the presence or absence of date of tumor recurrence detection. In case of absence of empty tumor recurrence date it was considered that the participant had not experienced tumor recurrence. Participants with local tumor recurrence ('Was it local to the primary tumor?' answered 'yes'.) compared to participants with distant tumor recurrence (specification for other tumor location given).

Outcome measures

Outcome measures
Measure	Overall n=51 Participants Participants with histologically proven local advanced T3/T4 rectal carcinoma with or without nodal involvement who had participated in study ML18280 were enrolled and no active treatment was given during this study
Tumor Recurrence Rate (Local and Distant) Participants with Tumor Recurrence	16 participants
Tumor Recurrence Rate (Local and Distant) Participants with Tumor Recurrence- Local	4 participants
Tumor Recurrence Rate (Local and Distant) Participants with Tumor Recurrence- Distant	12 participants

SECONDARY outcome

Timeframe: Up to 5 years

The type of therapies administered after primary treatments (chemotherapy, surgery or radiation) was reported

Outcome measures

Outcome measures
Measure	Overall n=51 Participants Participants with histologically proven local advanced T3/T4 rectal carcinoma with or without nodal involvement who had participated in study ML18280 were enrolled and no active treatment was given during this study
Type of Adjuvant Chemotherapy Folfox	2 participants
Type of Adjuvant Chemotherapy Xelox	10 participants
Type of Adjuvant Chemotherapy Xeloda mono or 5-FU mono	14 participants
Type of Adjuvant Chemotherapy Other (Biologics)	2 participants
Type of Adjuvant Chemotherapy Xeloda + Irinotecan	2 participants
Type of Adjuvant Chemotherapy No adjuvant chemotherapy	21 participants

SECONDARY outcome

Timeframe: Up to 5 years

The length of adjuvant chemotherapy was defined as time between first start date to last stop date of adjuvant chemotherapy regimen. Length of adjuvant chemotherapy was calculated as length \[days\] = last stop date - first start date + 1, missing day of start and stop date was replaced by 1.

Outcome measures

Outcome measures
Measure	Overall n=51 Participants Participants with histologically proven local advanced T3/T4 rectal carcinoma with or without nodal involvement who had participated in study ML18280 were enrolled and no active treatment was given during this study
Length of Adjuvant Chemotherapy	49.0 days Interval 0.0 to 1149.0

SECONDARY outcome

Timeframe: Up to 5 years

The surveillance compliance was calculated per participant in percent and frequencies for methods of diagnostic procedure adhered to, taking into account all expected procedures in the time span the participant participated and was based on the Swiss Society of Gastroenterology (SGG) follow-up care recommendations

Outcome measures

Outcome measures
Measure	Overall n=51 Participants Participants with histologically proven local advanced T3/T4 rectal carcinoma with or without nodal involvement who had participated in study ML18280 were enrolled and no active treatment was given during this study
Compliance to Diagnostic Procedures in Surveillance X-ray Chest	32 participants
Compliance to Diagnostic Procedures in Surveillance Colonoscopy	40 participants
Compliance to Diagnostic Procedures in Surveillance Computed Tomography (CT)	61 participants
Compliance to Diagnostic Procedures in Surveillance Endosonography	30 participants
Compliance to Diagnostic Procedures in Surveillance Magnetic resonance imaging	14 participants
Compliance to Diagnostic Procedures in Surveillance Unknown	1 participants
Compliance to Diagnostic Procedures in Surveillance Balloon Dilatation (BD) Ileostoma	1 participants
Compliance to Diagnostic Procedures in Surveillance BD Ileostoma+ Oesophagus-Gastroduodenum	1 participants
Compliance to Diagnostic Procedures in Surveillance Colon monocontrast	1 participants
Compliance to Diagnostic Procedures in Surveillance Colonoscopy Polypectomy	1 participants
Compliance to Diagnostic Procedures in Surveillance CT Abdomen	1 participants
Compliance to Diagnostic Procedures in Surveillance CT Thorax + Abdomen	1 participants
Compliance to Diagnostic Procedures in Surveillance Densitometry	1 participants
Compliance to Diagnostic Procedures in Surveillance Duplex Sonography	1 participants
Compliance to Diagnostic Procedures in Surveillance Enteroscopy	1 participants
Compliance to Diagnostic Procedures in Surveillance Ergometry	1 participants
Compliance to Diagnostic Procedures in Surveillance Oesophagus-gastroduodenoscopy	4 participants
Compliance to Diagnostic Procedures in Surveillance Fine Needle Puncture Lung	1 participants
Compliance to Diagnostic Procedures in Surveillance Gastroduodenoscopy	3 participants
Compliance to Diagnostic Procedures in Surveillance Gastrophinpassage	1 participants
Compliance to Diagnostic Procedures in Surveillance Gastroscopy	1 participants
Compliance to Diagnostic Procedures in Surveillance Ileocoloscopy	2 participants
Compliance to Diagnostic Procedures in Surveillance Ileoscopy	1 participants
Compliance to Diagnostic Procedures in Surveillance X-ray Lumbar Spine	1 participants
Compliance to Diagnostic Procedures in Surveillance Manometry	2 participants
Compliance to Diagnostic Procedures in Surveillance X-ray Pelvis	1 participants
Compliance to Diagnostic Procedures in Surveillance Positron emission tomography (PET)	1 participants
Compliance to Diagnostic Procedures in Surveillance PET-CT	11 participants
Compliance to Diagnostic Procedures in Surveillance Proctoscopy	2 participants
Compliance to Diagnostic Procedures in Surveillance Rectoproctoscopy	3 participants
Compliance to Diagnostic Procedures in Surveillance Rectoscopy	7 participants
Compliance to Diagnostic Procedures in Surveillance Rectosigmoidoscopy	4 participants
Compliance to Diagnostic Procedures in Surveillance Scintigraphy	1 participants
Compliance to Diagnostic Procedures in Surveillance Scintigraphy Lung	1 participants
Compliance to Diagnostic Procedures in Surveillance Sigmoidoscopy	2 participants
Compliance to Diagnostic Procedures in Surveillance Sonography	6 participants
Compliance to Diagnostic Procedures in Surveillance Starre Rectoscopy	1 participants
Compliance to Diagnostic Procedures in Surveillance Scintigraphy Bone Scan	1 participants
Compliance to Diagnostic Procedures in Surveillance Ultrasound	6 participants
Compliance to Diagnostic Procedures in Surveillance Ultrasound Abdomen	5 participants
Compliance to Diagnostic Procedures in Surveillance Video Bronchoscopy	1 participants
Compliance to Diagnostic Procedures in Surveillance X-ray Abdomen	3 participants
Compliance to Diagnostic Procedures in Surveillance X-ray Barium Swallow	1 participants
Compliance to Diagnostic Procedures in Surveillance X-ray Spine	1 participants

SECONDARY outcome

Timeframe: Up to 5 years

Long term side effects for bowel and urinary function was assessed. Bowel function was assessed in terms of mean bowel frequency, regular use of constipating agents as well as fecal incontinence. Urinary function was evaluated according to the presence (YES or NO) of incontinence. Overall participant satisfaction was assessed in terms of satisfaction with bowel, stoma and urinary function on a 4-stage scale (very good, good, poor, and very poor). In case of different assessment(s) of bowel or urinary function within the same surveillance period, the assessment with worst grade was documented and reported.

Outcome measures

Outcome measures
Measure	Overall n=51 Participants Participants with histologically proven local advanced T3/T4 rectal carcinoma with or without nodal involvement who had participated in study ML18280 were enrolled and no active treatment was given during this study
Long Term Side Effects Bowel frequency, <3	13 participants
Long Term Side Effects Bowel frequency, 3-5	8 participants
Long Term Side Effects Bowel frequency, 6-9	5 participants
Long Term Side Effects Bowel frequency, >9	1 participants
Long Term Side Effects Use of constipating agents	16 participants
Long Term Side Effects Fecal incontinence	17 participants
Long Term Side Effects Urinary incontinence	2 participants
Long Term Side Effects Overall participant satisfaction, very good	2 participants
Long Term Side Effects Overall participant satisfaction, good	10 participants
Long Term Side Effects Overall participant satisfaction, poor	8 participants
Long Term Side Effects Overall participant satisfaction, very poor	6 participants

SECONDARY outcome

Timeframe: Up to 5 years

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event in the investigator's judgment or requires intervention to prevent one or other of these outcomes

Outcome measures

Outcome measures
Measure	Overall n=51 Participants Participants with histologically proven local advanced T3/T4 rectal carcinoma with or without nodal involvement who had participated in study ML18280 were enrolled and no active treatment was given during this study
Incidence of Adverse Event (AE) and Serious Adverse Event (SAE) Number of participants with AE	4 participants
Incidence of Adverse Event (AE) and Serious Adverse Event (SAE) Number of participants with SAE	1 participants

Adverse Events

Overall

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Overall n=51 participants at risk Participants with histologically proven local advanced T3/T4 rectal carcinoma with or without nodal involvement who had participated in study ML18280 were enrolled and no active treatment was given during this study
Nervous system disorders Polyneuropathy	2.0% 1/51 • Up to 5 years An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	2.0% 1/51 • Up to 5 years An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Other adverse events

Other adverse events
Measure	Overall n=51 participants at risk Participants with histologically proven local advanced T3/T4 rectal carcinoma with or without nodal involvement who had participated in study ML18280 were enrolled and no active treatment was given during this study
Gastrointestinal disorders Constipation	2.0% 1/51 • Up to 5 years An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Gastrointestinal disorders Nausea	2.0% 1/51 • Up to 5 years An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	3.9% 2/51 • Up to 5 years An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Immune system disorders Hypersensitivity	2.0% 1/51 • Up to 5 years An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Additional Information

Roche Trial Information Hotline

F. Hoffmann-La Roche AG

Phone: +41 61 6878333

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER