A Study of Oxaliplatin and Capecitabine in Unresectable Metastatic Hepatocellular Cancer

• Sponsor: City of Hope Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03026803
• Collaborator: Sanofi (Industry)
• Enrollment: 4
• Location: 1
• Arm: 1
• Duration (Months): 95
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial is studying how well giving oxaliplatin and capecitabine together works in treating patients with liver cancer.

Condition or Disease	Intervention/Treatment	Phase
Liver Cancer; Hepatocellular Cancer	Drug: Oxaliplatin; Drug: Capecitabine	Phase 2

Detailed Description

Drugs used in chemotherapy, such as oxaliplatin and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving these drugs together may kill more tumor cells.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Oxaliplatin and Capecitabine in Unresectable Metastatic Hepatocellular Cancer
• Study Start Date: Nov 1, 2006
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oxaliplatin and Capecitabine 21 day cycle with Oxaliplatin 50mg/m2 day 1 and day 8 administered IV, Capecitabine 750 mg/m2 bid p.o. daily from day 1 to day 14	Drug: Oxaliplatin; Given IV; Other Names: Eloxatin ; Drug: Capecitabine; Given PO; Other Names: Xeloda

Outcome Measures

Primary Outcome Measures

1. Response Rate [Up to 2 years]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have histologically confirmed hepatocellular carcinoma which is recurrent, metastatic or unresectable.

• Patients may have up to two prior chemotherapy regimes. In addition, they may have had previous radiation, chemoembolization, and/or alcohol injections.

• Patients must have measurable disease, defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, and which has clearly progressed during the observation interval prior to participation in this study. Pleural effusions and ascites will not be considered measurable, but may be present in addition to the measurable lesion(s).

• Karnofsky performance status > 70%.

• Patients should have an expected survival of at least 2 months.

• Leukocytes >3,000/µl

• Absolute neutrophil count >1,500/µl

• Platelets >50,000/µl

• Total bilirubin < 3.0 g/dl

• AST (aspartate aminotransferase) (serum glutamic oxaloacetic transaminase(SGOT)/ALT (alanine aminotransferase) (serum glutamic pyruvic transaminase)(SGPT) < 5 times institutional upper limit of normal

• Creatinine < 2.0 OR measured or calculated creatinine clearance >60 mL/min for patients with creatinine levels above institutional normal

• Brain metastasis is not an exclusion, however, patients are only eligible if they have had successful control of the brain tumor(s) by surgery or stereotactic RT.

• Patients with no evidence of clinically significant neuropathy.

• All prior therapy must have been completed at least 4 weeks prior to the patient's entry on this trial.

• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

• Breastfeeding should be discontinued if the mother is treated with oxaliplatin.

• Subjects with chronic hepatitis B or C may be undergoing treatment with α interferon and/or ribavirin, as long as they meet the other criteria for entry on to this study.

• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Patients have prior oxaliplatin or xeloda treatment or undergoing therapy with other investigational agents.

• History of allergy to platinum compounds or to antiemetics appropriate for administration in conjunction with protocol-directed chemotherapy.

• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, or unstable angina pectoris, or cardiac arrhythmia.

• HIV-positive patients receiving anti-retroviral therapy (HAART) are excluded from the study because of possible pharmacokinetic interactions.

• Patients with a diagnosis of pulmonary fibrosis or a pulmonary interstitial process.

• Patients unable to swallow capecitabine will be excluded from this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Medical Center	Duarte	California	United States	91010

Sponsors and Collaborators

• City of Hope Medical Center
• Sanofi

Investigators

• Principal Investigator: Yun Yen, MD, City of Hope Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: City of Hope Medical Center
• ClinicalTrials.gov Identifier: NCT03026803
• Other Study ID Numbers: 05195
• First Posted: Jan 20, 2017
• Last Update Posted: Apr 13, 2017
• Last Verified: Mar 1, 2017

• Additional relevant MeSH terms: Liver Neoplasms; Carcinoma, Hepatocellular; Capecitabine; Oxaliplatin

Study Results

Participant Flow

Arm/Group Title	Oxaliplatin and Capecitabine
Arm/Group Description	21 day cycle with Oxaliplatin 50mg/m^2 day 1 and day 8 administered IV, Capecitabine 750 mg/m^2 bid p.o. daily from day 1 to day 14 Oxaliplatin: Given IV Capecitabine: Given PO
Period Title: Overall Study
STARTED	4
COMPLETED	4
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Oxaliplatin and Capecitabine
Arm/Group Description	21 day cycle with Oxaliplatin 50mg/m^2 day 1 and day 8 administered IV, Capecitabine 750 mg/m^2 bid p.o. daily from day 1 to day 14 Oxaliplatin: Given IV Capecitabine: Given PO
Overall Participants	4
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	71
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	4 100%
Region of Enrollment (participants) [Number]
United States	4 100%

Outcome Measures

1. Primary Outcome

Title	Response Rate
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxaliplatin and Capecitabine
Arm/Group Description	21 day cycle with Oxaliplatin 50mg/m^2 day 1 and day 8 administered IV, Capecitabine 750 mg/m^2 bid p.o. daily from day 1 to day 14 Oxaliplatin: Given IV Capecitabine: Given PO
Measure Participants	4
Number [percentage of participants]	0 0%

Adverse Events

Time Frame	Adverse events occurred over a period of 3 months.
Adverse Event Reporting Description	"Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Arm/Group Title	Oxaliplatin and Capecitabine
Arm/Group Description	21 day cycle with Oxaliplatin 50mg/m^2 day 1 and day 8 administered IV, Capecitabine 750 mg/m^2 bid p.o. daily from day 1 to day 14 Oxaliplatin: Given IV Capecitabine: Given PO
All Cause Mortality
	Oxaliplatin and Capecitabine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Oxaliplatin and Capecitabine
	Affected / at Risk (%)	# Events
Total	1/4 (25%)
Infections and infestations
Colitis, infectious (e.g., Clostridium difficile)	1/4 (25%)	1
Other (Not Including Serious) Adverse Events
	Oxaliplatin and Capecitabine
	Affected / at Risk (%)	# Events
Total	2/4 (50%)
Blood and lymphatic system disorders
Hemoglobin decreased	1/4 (25%)	1
Gastrointestinal disorders
Abdominal distension	1/4 (25%)	1
Abdominal pain	2/4 (50%)	3
Constipation	1/4 (25%)	2
Diarrhea	2/4 (50%)	3
Flatulence	1/4 (25%)	1
Gastrointestinal disorder	1/4 (25%)	1
Lower gastrointestinal hemorrhage	1/4 (25%)	1
Nausea	2/4 (50%)	2
Stomach pain	1/4 (25%)	1
General disorders
Chills	1/4 (25%)	1
Fatigue	2/4 (50%)	4
Fever	1/4 (25%)	1
Injection site reaction	1/4 (25%)	1
Pain	1/4 (25%)	1
Infections and infestations
Colitis, infectious (e.g., Clostridium difficile)	1/4 (25%)	1
Investigations
Alanine aminotransferase increased	2/4 (50%)	4
Alkaline phosphatase increased	2/4 (50%)	4
Aspartate aminotransferase increased	2/4 (50%)	4
Creatinine increased	2/4 (50%)	3
Leukocyte count decreased	1/4 (25%)	1
Lymphocyte count decreased	1/4 (25%)	1
Platelet count decreased	1/4 (25%)	3
Metabolism and nutrition disorders
Anorexia	2/4 (50%)	2
Blood glucose increased	2/4 (50%)	4
Blood uric acid increased	2/4 (50%)	4
Dehydration	1/4 (25%)	1
Serum albumin decreased	2/4 (50%)	4
Serum calcium decreased	1/4 (25%)	1
Serum calcium increased	1/4 (25%)	1
Serum magnesium decreased	2/4 (50%)	2
Serum phosphate decreased	1/4 (25%)	2
Serum potassium decreased	1/4 (25%)	1
Serum potassium increased	1/4 (25%)	2
Musculoskeletal and connective tissue disorders
Back pain	1/4 (25%)	1
Muscle weakness	1/4 (25%)	1
Pain in extremity	1/4 (25%)	1
Nervous system disorders
Dizziness	1/4 (25%)	2
Headache	2/4 (50%)	2
Peripheral sensory neuropathy	2/4 (50%)	6
Taste alteration	1/4 (25%)	1
Psychiatric disorders
Anxiety	1/4 (25%)	1
Insomnia	1/4 (25%)	1
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain	1/4 (25%)	1
Voice alteration	2/4 (50%)	2
Skin and subcutaneous tissue disorders
Pruritus	2/4 (50%)	3
Rash desquamating	2/4 (50%)	5
Vascular disorders
Flushing	1/4 (25%)	1

Limitations/Caveats

Due to Sorafenib becoming a first line treatment for HCC, the designed treatment became less competitive. The company Sanofi decided not to continue support. Study was terminated after accrual of 4 of the 32 planned patients.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.