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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)

Phase 2
18 Years
Open (Enrolling)
Colorectal Cancer

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Trial Information

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)



- To assess the progression-free survival (PFS) of patients with metastatic colorectal
carcinoma treated with hydroxychloroquine in combination with capecitabine,
oxaliplatin, and bevacizumab and to compare this to a previously reported median PFS of
7.9 months.


- To measure the overall response rate.

- To measure the duration of response for responding patients.

- To measure the disease-control rate (complete response, partial response, or stable
disease for at least 2 courses).

- To document the safety and feasibility of this regimen in these patients.

- To develop surrogate biomarkers for autophagy detection in patient tissue specimens and
to characterize the effects of hydroxychloroquine on autophagy in patients in vivo.

OUTLINE: This is a multicenter study.

Patients receive bevacizumab IV over 30-90 minutes and oxaliplatin IV over 2 hours on day 1.
Patients also receive oral capecitabine twice daily on days 1-15 and oral hydroxychloroquine
twice daily on days 1-21. Courses repeat every 21 days in the absence of disease progression
or unacceptable toxicity.

Peripheral blood and tumor tissue samples may be collected for biomarker and other
laboratory studies.

After completion of study treatment, patients are followed up for 1 year.

Inclusion Criteria


- 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


- 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


- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival

Outcome Time Frame:

4 years

Safety Issue:


Principal Investigator

Rebecca A. Moss, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer Institute of New Jersey


United States: Institutional Review Board

Study ID:




Start Date:

May 2009

Completion Date:

May 2014

Related Keywords:

  • Colorectal Cancer
  • stage IV colon cancer
  • stage IV rectal cancer
  • recurrent colon cancer
  • recurrent rectal cancer
  • Colorectal Neoplasms



Cancer Institute of New Jersey at Hamilton Hamilton, New Jersey  08690
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School New Brunswick, New Jersey  08903
New Jersey Medical School/The University Hospital Cancer Center Newark, New Jersey  07103