Hydroxychloroquine, Capecitabine, Oxaliplatin, and Bevacizumab in Treating Patients With Metastatic Colorectal Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT01006369
• Date of registration: 30/10/2009
• Primary sponsor: University of Medicine and Dentistry New Jersey
• Public title: Hydroxychloroquine, Capecitabine, Oxaliplatin, and Bevacizumab in Treating Patients With Metastatic Colorectal Cancer
• Scientific title: Autophagy and Anti-Angiogenesis in Metastatic Colorectal Carcinoma: A Phase II Trial of Hydroxychloroquine to Augment Effectiveness of XELOX-Bevacizumab. A Study of the Cancer Institute of New Jersey Oncology Group (CINJOG)
• Date of first enrolment: May 2009
• Target sample size: 47
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT01006369
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Rebecca A. Moss, MD
• Affiliation: Cancer Institute of New Jersey

Key inclusion & exclusion criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed colorectal carcinoma

- Metastatic disease

- Measurable disease, defined as = 1 lesion that can be accurately measured in = 1
dimension (longest diameter to be recorded) as > 20 mm by conventional techniques or
> 10 mm by spiral CT scan

- Brain metastases allowed provided they have been treated and stable for > 4 weeks

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Life expectancy = 12 weeks

- ANC = 1,500/mm^3

- Platelet count = 100,000/mm^3

- AST/ALT = 3 times upper limit of normal (ULN)

- Total bilirubin = 1.5 times ULN

- PT (INR) = 1.5

- Creatinine < 1.5 times ULN

- Creatinine clearance = 30 mL/min

- Urine protein:creatinine ratio < 1.0 OR < 1 g protein by 24-hour urine collection

- Not on dialysis

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception before, during, and for 4 weeks
after completion of study treatment

- Prior non-colonic malignancies allowed provided there is no current clinical evidence
of persistent or recurrent disease AND the patient is not on active therapy,
including hormonal therapy

- No uncontrolled hypertension, defined as systolic BP > 150 mm Hg or diastolic BP > 90
mm Hg, despite antihypertensive medications

- No cardiac disease, including any of the following:

- NYHA class III-IV congestive heart failure

- Unstable angina (anginal symptoms at rest)

- New onset angina (began within the past 3 months)

- Myocardial infarction within the past 6 months

- Uncontrolled arrhythmia

- No thrombolic or embolic events (e.g., cerebrovascular accident including transient
ischemic attacks) within the past 6 months

- No serious non-healing wound, ulcer, or bone fracture

- No significant traumatic injury within the past 28 days

- No neuropathy = grade 2

- No evidence of bleeding diathesis or coagulopathy

- No condition that would impair the patient's ability to swallow whole pills

- No malabsorption problem

- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 6 months

- No known G-6PD deficiency

- No retinal or visual field changes from prior 4-aminoquinoline compound use

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to capecitabine or hydroxychloroquine

- No other concurrent serious systemic disorders (including active infections) that, in
the investigator's opinion, would compromise the safety of the patient or compromise
the patient's ability to complete the study

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior chemotherapy for metastatic disease, except for adjuvant therapy that was
completed = 6 months before the first evidence of metastasis

- More than 28 days since prior major surgical procedure or open biopsy

- No concurrent anticoagulation with warfarin

- Concurrent low molecular weight heparin (or an equivalent drug) allowed

- No concurrent hydroxychloroquine for treatment or prophylaxis of malaria

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent St. John wort

- No other concurrent investigational or anticancer agents or therapies



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Colorectal Cancer

Intervention(s)

Biological: bevacizumab

Drug: hydroxychloroquine

Drug: XELOX regimen

Primary Outcome(s)

Progression-free survival [Time Frame: 4 years]

Secondary Outcome(s)

Biological activity of hydroxychloroquine as evidenced by Beclin-1, p62, and LC3 biomarker response in peripheral blood mononuclear cells [Time Frame: 4 years]

Disease-control rate [Time Frame: 4 years]

Duration of response [Time Frame: 4 years]

Overall response rate [Time Frame: 4 years]

Safety and feasibility [Time Frame: 4 years]

Secondary ID(s)

070806

CINJ-070806

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Cancer Institute (NCI)