A Study of Capecitabine [Xeloda] in Combination With Trastuzumab [Herceptin] and Oxaliplatine in Patients With Resectable Gastric Cancer

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01130337
• Collaborator: (none)
• Enrollment: 36
• Locations: 30
• Arm: 1
• Duration (Months): 47
• Patients Per Site: 1.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study will evaluate the disease free survival rate of a combination of capecitabine [Xeloda] and oxaliplatin (XELOX) with trastuzumab [Herceptin] in patients with resectable gastric cancer. The combination of Xeloda (orally, 1000 mg/m2 on day 1-14 of every cycle) and Herceptin (intravenously, 8 mg/kg loading dose, then 6 mg/kg on days 1-14 of every cycle) will be administered for three cycles prior to surgery to resect the tumor. If complete resection, R0 or microscopic residual tumor R1 is achieved, patients will continue with three cycles of XELOX and Herceptin and then for completion of 12 months treatment with Herceptin alone. Oxaliplatin will be administered intravenously at a dose of 130 mg/m2 on day 1 in every cycle. The anticipated time on study drug will be 12 months.

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer	Drug: Capecitabine [Xeloda]; Drug: Oxaliplatin; Drug: Trastuzumab [Herceptin]	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Multi-center Study to Evaluate the Disease Free Survival Rate of a Perioperative Combination of Capecitabine (Xeloda), Trastuzumab (Herceptin) and Oxaliplatin (XELOX- Trastuzumab) in Patients With Resectable Gastric or Gastro-esophageal Junction Adenocarcinoma
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Capecitabine [Xeloda]; 1.000 mg/m2 orally every 12 hours from day 1 to day 14 of every cycle for 6 cycles; Drug: Oxaliplatin; 130 mg/m2 intravenous infusion day 1 of every cycle; Drug: Trastuzumab [Herceptin]; First dose 8 mg/kg, subsequent cycles 6 mg/kg, intravenously, day of every cycle for 15 cycles

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Disease-free Survival (DFS) at Month 18 [Month 18]

   DFS was the time elapsed from the time of surgery (for complete resection [R0] participants) until the date on which progression or death from any cause was documented (whichever occured first). Progression was defined as target lesions greater than (>) 20 percent (%) increase in the sum of the longest diameter (SLD) taking as reference the smallest SLD recorded since the treatment started (nadir) and minimum 5 millimeter (mm) increase over the nadir. When the sum becomes very small, increases within the measurement error (2-3 mm) can lead to a 20% increase. Participants who did not present progression and who had not died were censored on the last date on which it was known that there was no progression (last response assessment).

Secondary Outcome Measures

1. Percentage of Participants With Pathological Complete Response (pCR) [Between Days 7 and 21 of the 3rd cycle of neoadjuvant treatment, thereafter, every 9 weeks during adjuvant treatment and then after adjuvant treatment every 3 months until Month 25]

   pCR was defined as an absence of any invasive cancer cell of the primary tumor after the time of major neoadjuvant chemotherapy, with or without surgery.

2. Percentage of Participants With Complete Tumor Resection (R0) [Between Days 7 and 21 of the 3rd cycle of neoadjuvant treatment, thereafter, every 9 weeks during adjuvant treatment and then after adjuvant treatment every 3 months until Month 25]

   R0 resection was defined as having performed a complete resection of the tumor with adequate tumor-free margins and regional lymph node extirpation.

3. Percentage of Participants With Objective Response [Between Days 7 and 21 of the 3rd cycle of neoadjuvant treatment, thereafter, every 9 weeks during adjuvant treatment and then after adjuvant treatment every 3 months until Month 25]

   An objective response was defined as either a complete response (CR) or a partial response (PR). Using the Response Evaluation Criteria in Solid Tumors (RECIST), CR was defined as the disappearance of all target lesions and all non-target lesions, normalization of tumor marker level, and no new lesions. PR was defined as the disappearance of all target lesions and persistence of greater than or equal to (≥) 1 non-target lesions and/or the maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diameter of target lesions, and no new lesions or unequivocal progression of existing non-target lesions.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult patients over 18 years of age

• Locally advanced resectable HER2-positive gastric or esophagogastric junction adenocarcinoma (Sievert types I, II, III)

• Measurable (RECIST criteria) or assessable disease

• ECOG performance 0-2

• Life expectancy of 12 weeks or more

Exclusion Criteria:

• Immeasurable lesion as the only evidence of disease

• Previous chemotherapy or radiotherapy for gastric neoplasm or some kind of previous surgical resection of the tumor (except diagnostic laparoscopy)

• Concomitant heart disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Elche	Alicante	Spain	03203
2		Oviedo	Asturias	Spain	33006
3		Santander	Cantabria	Spain	39008
4		San Sebastian	Guipuzcoa	Spain	20014
5		Palma de Mallorca	Islas Baleares	Spain	07198
6		Vigo	Pontevedra	Spain	36204
7		La Laguna	Tenerife	Spain	38320
8		Barakaldo	Vizcaya	Spain	48903
9		Barcelona		Spain	08003
10		Barcelona		Spain	08035
11		Barcelona		Spain	08036
12		Barcelona		Spain	08907
13		Barcelona		Spain	08916
14		Burgos		Spain	09006
15		Cordoba		Spain	14004
16		Granada		Spain	18014
17		La Coruña		Spain	15006
18		Leon		Spain	24071
19		Lerida		Spain	25198
20		Lugo		Spain	27003
21		Madrid		Spain	28007
22		Madrid		Spain	28040
23		Madrid		Spain	28041
24		Orense		Spain	32005
25		Sevilla		Spain	41013
26		Sevilla		Spain	41014
27		Toledo		Spain	45004
28		Valencia		Spain	46009
29		Valencia		Spain	46014
30		Zaragoza		Spain	50009

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01130337
• Other Study ID Numbers: ML25189
• First Posted: May 26, 2010
• Last Update Posted: Oct 1, 2015
• Last Verified: Sep 1, 2015

• Additional relevant MeSH terms: Stomach Neoplasms; Capecitabine; Oxaliplatin; Trastuzumab

Study Results

Participant Flow

Pre-assignment Detail	Screening period comprised of 35 days. A total of 136 participants were included in the study, of which 36 participants were enrolled and 100 participants discontinued due to screening failures. Abbreviation of AE= adverse event.

Arm/Group Title	Capecitabine+Oxaliplatin+Trastuzumab
Arm/Group Description	Participants received 3 cycles of capecitabine (1,000 milligrams per meter squared [mg/m^2] tablet orally [p.o] twice daily, Days 1-14)/oxaliplatin (130 mg/m^2 as a 120-minute intravenous [IV] infusion, Day 1 of the cycle)/trastuzumab (8 milligrams per kilograms [mg/kg] on Day 1, followed by doses of 6 mg/kg as IV infusion) (XELOX-trastuzumab) as neoadjuvant treatment, every 3 weeks, thereafter, they were assessed for surgery. After surgery, participants received 3 cycles of XELOX-trastuzumab as treatment adjuvant to the surgery, thereafter, another 12 cycles of trastuzumab as monotherapy, was administered every 3 weeks, until disease progression or death.
Period Title: Overall Study
STARTED	36
COMPLETED	22
NOT COMPLETED	14

Baseline Characteristics

Arm/Group Title	Capecitabine+Oxaliplatin+Trastuzumab
Arm/Group Description	Participants received 3 cycles of capecitabine (1,000 mg/m^2 tablet p.o twice daily, Days 1-14)/oxaliplatin (130 mg/m^2 as a 120-minute IV infusion Day 1 of the cycle)/trastuzumab (8 mg/kg on Day 1, followed by doses of 6 mg/kg as IV infusion) (XELOX-trastuzumab) as neoadjuvant treatment, every 3 weeks, thereafter, they were assessed for surgery. After surgery, participants received 3 cycles of XELOX-trastuzumab as treatment adjuvant to the surgery, thereafter, another 12 cycles of trastuzumab as monotherapy, was administered every 3 weeks, until disease progression or death.
Overall Participants	36
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.44 (10.42)
Sex: Female, Male (Count of Participants)
Female	7 19.4%
Male	29 80.6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Disease-free Survival (DFS) at Month 18
Description	DFS was the time elapsed from the time of surgery (for complete resection [R0] participants) until the date on which progression or death from any cause was documented (whichever occured first). Progression was defined as target lesions greater than (>) 20 percent (%) increase in the sum of the longest diameter (SLD) taking as reference the smallest SLD recorded since the treatment started (nadir) and minimum 5 millimeter (mm) increase over the nadir. When the sum becomes very small, increases within the measurement error (2-3 mm) can lead to a 20% increase. Participants who did not present progression and who had not died were censored on the last date on which it was known that there was no progression (last response assessment).
Time Frame	Month 18

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Capecitabine+Oxaliplatin+Trastuzumab
Arm/Group Description	Participants received 3 cycles of capecitabine (1,000 mg/m^2 tablet p.o twice daily, Days 1-14)/oxaliplatin (130 mg/m^2 as a 120-minute IV infusion Day 1 of the cycle)/trastuzumab (8 mg/kg on Day 1, followed by doses of 6 mg/kg as IV infusion) (XELOX-trastuzumab) as neoadjuvant treatment, every 3 weeks, thereafter, they were assessed for surgery. After surgery, participants received 3 cycles of XELOX-trastuzumab as treatment adjuvant to the surgery, thereafter, another 12 cycles of trastuzumab as monotherapy, was administered every 3 weeks, until disease progression or death.
Measure Participants	36
Number (95% Confidence Interval) [percentage of participants]	76.12 211.4%

2. Secondary Outcome

Title	Percentage of Participants With Pathological Complete Response (pCR)
Description	pCR was defined as an absence of any invasive cancer cell of the primary tumor after the time of major neoadjuvant chemotherapy, with or without surgery.
Time Frame	Between Days 7 and 21 of the 3rd cycle of neoadjuvant treatment, thereafter, every 9 weeks during adjuvant treatment and then after adjuvant treatment every 3 months until Month 25

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Capecitabine+Oxaliplatin+Trastuzumab
Arm/Group Description	Participants received 3 cycles of capecitabine (1,000 mg/m^2 tablet p.o twice daily, Days 1-14)/oxaliplatin (130 mg/m^2 as a 120-minute IV infusion Day 1 of the cycle)/trastuzumab (8 mg/kg on Day 1, followed by doses of 6 mg/kg as IV infusion) (XELOX-trastuzumab) as neoadjuvant treatment, every 3 weeks, thereafter, they were assessed for surgery. After surgery, participants received 3 cycles of XELOX-trastuzumab as treatment adjuvant to the surgery, thereafter, another 12 cycles of trastuzumab as monotherapy, was administered every 3 weeks, until disease progression or death.
Measure Participants	36
Number (95% Confidence Interval) [percentage of participants]	8.33 23.1%

3. Secondary Outcome

Title	Percentage of Participants With Complete Tumor Resection (R0)
Description	R0 resection was defined as having performed a complete resection of the tumor with adequate tumor-free margins and regional lymph node extirpation.
Time Frame	Between Days 7 and 21 of the 3rd cycle of neoadjuvant treatment, thereafter, every 9 weeks during adjuvant treatment and then after adjuvant treatment every 3 months until Month 25

Outcome Measure Data

Analysis Population Description

ITT population. Here "number of participants analyzed" included those who underwent surgery.

Arm/Group Title	Capecitabine+Oxaliplatin+Trastuzumab
Arm/Group Description	Participants received 3 cycles of capecitabine (1,000 mg/m^2 tablet p.o twice daily, Days 1-14)/oxaliplatin (130 mg/m^2 as a 120-minute IV infusion Day 1 of the cycle)/trastuzumab (8 mg/kg on Day 1, followed by doses of 6 mg/kg as IV infusion) (XELOX-trastuzumab) as neoadjuvant treatment, every 3 weeks, thereafter, they were assessed for surgery. After surgery, participants received 3 cycles of XELOX-trastuzumab as treatment adjuvant to the surgery, thereafter, another 12 cycles of trastuzumab as monotherapy, was administered every 3 weeks, until disease progression or death.
Measure Participants	31
Number (95% Confidence Interval) [percentage of participants]	90.32 250.9%

4. Secondary Outcome

Title	Percentage of Participants With Objective Response
Description	An objective response was defined as either a complete response (CR) or a partial response (PR). Using the Response Evaluation Criteria in Solid Tumors (RECIST), CR was defined as the disappearance of all target lesions and all non-target lesions, normalization of tumor marker level, and no new lesions. PR was defined as the disappearance of all target lesions and persistence of greater than or equal to (≥) 1 non-target lesions and/or the maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diameter of target lesions, and no new lesions or unequivocal progression of existing non-target lesions.
Time Frame	Between Days 7 and 21 of the 3rd cycle of neoadjuvant treatment, thereafter, every 9 weeks during adjuvant treatment and then after adjuvant treatment every 3 months until Month 25

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Capecitabine+Oxaliplatin+Trastuzumab
Arm/Group Description	Participants received 3 cycles of capecitabine (1,000 mg/m^2 tablet p.o twice daily, Days 1-14)/oxaliplatin (130 mg/m^2 as a 120-minute IV infusion Day 1 of the cycle)/trastuzumab (8 mg/kg on Day 1, followed by doses of 6 mg/kg as IV infusion) (XELOX-trastuzumab) as neoadjuvant treatment, every 3 weeks, thereafter, they were assessed for surgery. After surgery, participants received 3 cycles of XELOX-trastuzumab as treatment adjuvant to the surgery, thereafter, another 12 cycles of trastuzumab as monotherapy, was administered every 3 weeks, until disease progression or death.
Measure Participants	36
Number [percentage of participants]	38.89 108%

Adverse Events

Time Frame	Before Day 1 of each cycle until Month 25
Adverse Event Reporting Description	The safety analysis included all participants in the ITT population who received at least 1 dose of the study drugs.
Arm/Group Title	Capecitabine+Oxaliplatin+Trastuzumab
Arm/Group Description	Participants received 3 cycles of capecitabine (1,000 mg/m^2 tablet p.o twice daily, Days 1-14)/oxaliplatin (130 mg/m^2 as a 120-minute IV infusion Day 1 of the cycle)/trastuzumab (8 mg/kg on Day 1, followed by doses of 6 mg/kg as IV infusion) (XELOX-trastuzumab) as neoadjuvant treatment, every 3 weeks, thereafter, they were assessed for surgery. After surgery, participants received 3 cycles of XELOX-trastuzumab as treatment adjuvant to the surgery, thereafter, another 12 cycles of trastuzumab as monotherapy, was administered every 3 weeks, until disease progression or death.
All Cause Mortality
	Capecitabine+Oxaliplatin+Trastuzumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Capecitabine+Oxaliplatin+Trastuzumab
	Affected / at Risk (%)	# Events
Total	22/36 (61.1%)
Cardiac disorders
Cardiogenic shock	1/36 (2.8%)	1
Gastrointestinal disorders
Diarrhoea	5/36 (13.9%)	6
Dysphagia	1/36 (2.8%)	1
Intestinal ischaemia	1/36 (2.8%)	1
Intestinal obstruction	1/36 (2.8%)	1
Localised intra-abdominal fluid collection	2/36 (5.6%)	2
Oesophageal perforation	1/36 (2.8%)	1
Vomiting	1/36 (2.8%)	1
General disorders
Mucosal inflammation	1/36 (2.8%)	1
Multi-organ failure	1/36 (2.8%)	1
Pyrexia	1/36 (2.8%)	1
Sudden death	1/36 (2.8%)	1
Infections and infestations
Abdominal sepsis	1/36 (2.8%)	1
Appendicitis	1/36 (2.8%)	1
Pneumonia	2/36 (5.6%)	2
Postoperative wound infection	1/36 (2.8%)	1
Sepsis	1/36 (2.8%)	1
Septic shock	1/36 (2.8%)	1
Injury, poisoning and procedural complications
Anastomotic leak	1/36 (2.8%)	1
Procedural complication	1/36 (2.8%)	1
Nervous system disorders
Encephalopathy	1/36 (2.8%)	1
Psychiatric disorders
Schizoaffective disorder	1/36 (2.8%)	1
Renal and urinary disorders
Renal failure acute	1/36 (2.8%)	1
Respiratory, thoracic and mediastinal disorders
Pleural effusion	1/36 (2.8%)	1
Pneumothorax	2/36 (5.6%)	2
Vascular disorders
Hypovolaemic shock	1/36 (2.8%)	1
Peripheral ischaemia	1/36 (2.8%)	1
Other (Not Including Serious) Adverse Events
	Capecitabine+Oxaliplatin+Trastuzumab
	Affected / at Risk (%)	# Events
Total	35/36 (97.2%)
Blood and lymphatic system disorders
Anaemia	11/36 (30.6%)	13
Neutropenia	7/36 (19.4%)	16
Thrombocytopenia	4/36 (11.1%)	16
Gastrointestinal disorders
Abdominal pain	9/36 (25%)	12
Abdominal pain upper	5/36 (13.9%)	8
Constipation	6/36 (16.7%)	6
Diarrhoea	29/36 (80.6%)	68
Dyspepsia	3/36 (8.3%)	3
Dysphagia	5/36 (13.9%)	13
Gastrooesophageal reflux disease	2/36 (5.6%)	2
Nausea	17/36 (47.2%)	29
Vomiting	15/36 (41.7%)	26
General disorders
Asthenia	24/36 (66.7%)	61
Mucosal inflammation	8/36 (22.2%)	9
Pyrexia	10/36 (27.8%)	13
Hepatobiliary disorders
Hyperbilirubinaemia	3/36 (8.3%)	3
Investigations
Alanine aminotransferase increased	3/36 (8.3%)	5
Aspartate aminotransferase increased	2/36 (5.6%)	4
Ejection fraction decreased	2/36 (5.6%)	2
Metabolism and nutrition disorders
Decreased appetite	15/36 (41.7%)	30
Hypokalaemia	2/36 (5.6%)	4
Musculoskeletal and connective tissue disorders
Arthralgia	3/36 (8.3%)	5
Muscle spasms	2/36 (5.6%)	2
Pain in extremity	2/36 (5.6%)	2
Nervous system disorders
Dysaesthesia	7/36 (19.4%)	18
Dysgeusia	3/36 (8.3%)	5
Neuropathy peripheral	6/36 (16.7%)	9
Neurotoxicity	10/36 (27.8%)	16
Paraesthesia	6/36 (16.7%)	11
Peripheral sensory neuropathy	2/36 (5.6%)	6
Psychiatric disorders
Anxiety	2/36 (5.6%)	2
Respiratory, thoracic and mediastinal disorders
Catarrh	3/36 (8.3%)	7
Dyspnoea	3/36 (8.3%)	4
Epistaxis	3/36 (8.3%)	13
Rhinorrhoea	3/36 (8.3%)	3
Skin and subcutaneous tissue disorders
Erythema	2/36 (5.6%)	2
Nail disorder	3/36 (8.3%)	4
Palmar-plantar erythrodysaesthesia syndrome	2/36 (5.6%)	4
Pruritus	2/36 (5.6%)	2
Rash	2/36 (5.6%)	2
Vascular disorders
Hypertension	2/36 (5.6%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.