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

NCT01006369 | Completed Phase 2 Results

• 4 other identifiers: 0220090022CINJ-070806P30CA072720070806
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 4

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as capecitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Hydroxychloroquine may help chemotherapy and bevacizumab work better and kill more tumor cells. PURPOSE: This phase II trial is studying how well giving hydroxychloroquine together with capecitabine, oxaliplatin, and bevacizumab works in treating patients with metastatic colorectal cancer.

Conditions

Colorectal Cancer

Keywords

stage IV colon cancer; stage IV rectal cancer; recurrent colon cancer; recurrent rectal cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Computed Kaplan-Meier survival curve estimates for progression free survival (PFS) and compared to historical controls of median PFS of 240 days. Evaluated response using RECIST criteria every 12 weeks.

  6 years

Secondary Outcomes (2)

• Overall Response Rate

  6 years

• Overall Survival

  6 years

Study Arms (2)

FOLFOX6 + Bevacizumab + Hydroxychloroquine

EXPERIMENTAL

Arm A: FOLFOX6 + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 5 mg/kg in 100 cc Normal Saline every 14 days on day one. Drug: hydroxychloroquine hydroxychloroquine 200 mg po BID daily

Drug: hydroxychloroquine

XELOX + Bevacizumab + Hydroxychloroquine

EXPERIMENTAL

Arm B: XELOX + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 7.5 mg/kg in 100 cc Normal Saline every 21 days. Drug: hydroxychloroquine hydroxychloroquine 200 mg po BID daily

Drug: hydroxychloroquine

Interventions

hydroxychloroquine DRUG

hydroxychloroquine 200 mg po BID daily

FOLFOX6 + Bevacizumab + Hydroxychloroquine; XELOX + Bevacizumab + Hydroxychloroquine

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

Cooper Hospital/University Medical Center

Camden, New Jersey, 08103, United States

Location

Cancer Institute of New Jersey at Hamilton

Hamilton, New Jersey, 08690, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

New Jersey Medical School/The University Hospital Cancer Center

Newark, New Jersey, 07103, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Elizabeth Poplin MD
• Organization: Rutgers Cancer Institute of New Jersey

poplinea@cinj.rutgers.edu

732-235-7620

Study Officials

• Rebecca A. Moss, MD

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: October 30, 2009
• First Posted: November 2, 2009
• Study Start: May 1, 2009
• Primary Completion: August 6, 2015
• Study Completion: April 27, 2016
• Last Updated: September 21, 2021
• Results First Posted: March 11, 2021

Record last verified: 2021-09

Locations

US (4)