Dose Dense Therapy and Bevacizumab in Solid Tumors and Colorectal Cancer

NCT00296062 | Terminated Phase 1 DMC

• 4 other identifiers: CASE1205U01CA062502P30CA043703NCI-7325
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as capecitabine, irinotecan, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Bevacizumab may also block blood flow to the tumor. Giving combination chemotherapy together with bevacizumab may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of capecitabine when given together with irinotecan and oxaliplatin with or without bevacizumab and to see how well they work in treating patients with metastatic or locally advanced colorectal cancer or other solid tumors that cannot be removed by surgery.

Conditions

Colorectal Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specific; stage III colon cancer; stage IV colon cancer; stage III rectal cancer; stage IV rectal cancer; recurrent colon cancer; recurrent rectal cancer

Outcome Measures

Primary Outcomes (2)

• Phase II: Bevacizumab plus dose-intense capecitabine in combination with alternating full-dose irinotecan hydrochloride and oxaliplatin as first-line treatment leads to an improved response rate in patients with metastatic colorectal cancer

  Courses repeat every 28 days in the absence of unacceptable toxicity.

• Phase II: Determine the toxicity of bevacizumab in combination with this regimen in patients with metastatic colorectal cancer.

  at end of course 2 (each course is 28 days)

Secondary Outcomes (1)

• Phase I: Maximum tolerated dose in patients ≥ 65 years of age measured by CTC version 3.0 at end of Safety in the Elderly component of study

  Receive escalating doses of capecitabine (during both odd- and even-numbered courses) until the maximum tolerated dose (MTD) is determined.

Interventions

bevacizumab BIOLOGICAL

Phase II: IV over 30-90 minutes on days 1 and 15 of each course.

capecitabine DRUG

Phase I: oral capecitabine twice daily on days 1-7 and 15-21.Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of capecitabine (during both odd- and even-numbered courses) until the maximum tolerated dose (MTD) is determined.Phase II:receive capecitabine (at the MTD determined in phase I(odd-numbered courses)

irinotecan hydrochloride DRUG

Phase I: irinotecan hydrochloride IV over 90 minutes on days 1 and 15 during course 1 and all subsequent odd-numbered courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.Phase II: receive capecitabine (at the MTD determined in phase I) in combination with irinotecan hydrochloride (during odd-numbered courses)

oxaliplatin DRUG

Phase I: oxaliplatin IV over 2 hours on days 1 and 15 during course 2 and all subsequent even-numbered courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Phase II: oxaliplatin (during even-numbered courses) as in phase I

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Phase I: * Histologically or cytologically confirmed solid tumor * Metastatic OR locally advanced unresectable disease * No curative therapy exists * Measurable or evaluable disease * Measurable disease is defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension as ≥ 20 mm with conventional techniques OR ≥ 10 mm with spiral CT scan * No known brain metastases * Phase II: * Histologically or cytologically confirmed colorectal cancer * Metastatic OR locally advanced unresectable disease * Measurable disease (as defined in phase I) * No tumor involving major blood vessels * No evidence of CNS disease, including primary brain tumor or brain metastases PATIENT CHARACTERISTICS: * Karnofsky performance status 70-100% * Life expectancy ≥ 12 weeks * Absolute neutrophil count (ANC) ≥ 1,500/mm\^3 * ANC \< 1,500/mm\^3 allowed, if in the opinion of the investigator, this represents an ethnic or racial variation of normal * Platelet count ≥ 100,000/mm\^3 * Hemoglobin \> 10.0 g/dL * Bilirubin ≤ 1.5 mg/dL * AST/ALT ≤ 2 times upper limit of normal (ULN) * Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min * Urine protein:creatinine ratio \< 1.0 OR protein \< 1 g by 24-hour urine collection (phase II) * PT/INR ≤ 1.5 unless on full-dose anticoagulants (phase II) * Not pregnant or nursing * Negative pregnancy test * Fertile female patients must use effective double-barrier contraception during and for 28 days (phase I) or 3 months (phase II) after completion of study treatment * Fertile male patients must use effective contraception during and for 6 months after completion of study treatment * No history of allergic reaction attributed to compounds of similar chemical or biologic composition to capecitabine, irinotecan hydrochloride, oxaliplatin, or bevacizumab * No other uncontrolled illness including, but not limited to, any of the following: * Ongoing or active infection * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia * Psychiatric illness or social situation that would preclude study compliance * No cardiac ischemia within the past 6 months (phase I) * No New York Heart Association class II-IV congestive heart failure or symptomatic arrhythmia (phase II) * No arterial thrombotic events within the past 6 months including, but not limited to, any of the following (phase II): * Transient ischemic attack * Cerebrovascular accident * Unstable angina or angina requiring surgical or medical intervention * Myocardial infarction * No clinically significant peripheral vascular disease (phase II) * No history of hypertension unless well controlled (\< 150/90 mm Hg) on an antihypertensive regimen (phase II) * No evidence of bleeding diathesis or coagulopathy (phase II) * No gastrointestinal (GI) perforation, abdominal fistula, or intra-abdominal abscess within the past 30 days (phase II) * No significant history of bleeding events (phase II) * Patients with a history of significant bleeding episodes (e.g., hemoptysis or upper or lower GI bleeding) within the past 6 months are not eligible unless the source of bleeding has been resected * No significant traumatic injury within the past 28 days (phase II) * No serious or nonhealing wound, ulcer, or bone fracture (phase II) * No peripheral neuropathy \> grade 1 PRIOR CONCURRENT THERAPY: * At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered (phase I) * At least 2 weeks since prior immunotherapy or biologic therapy and recovered (phase I) * No prior treatment for advanced or metastatic colorectal cancer (phase II) * More than 12 months since prior adjuvant chemotherapy and/or biologic therapy (e.g., bevacizumab or cetuximab) and recovered (phase II) * At least 4 weeks since prior radiotherapy and recovered * No prior radiotherapy to the only site of measurable disease unless there is measurable disease progression within the radiation port after completion of radiotherapy * No prior radiotherapy to ≥ 20% of the bone marrow * More than 28 days since prior major surgical procedure\* or open biopsy and recovered (phase II) * More than 14 days since prior minor surgery\* and recovered (phase II) * Concurrent full-dose anticoagulation (e.g., warfarin) allowed provided the following criteria are met (phase II): * Patient has an in-range INR (between 2 and 3) and is on a stable dose of oral anticoagulants or a stable dose of low molecular weight heparin * No active bleeding or pathological condition that carries a high risk of bleeding (e.g., known varices) * No concurrent combination antiretroviral therapy for HIV-positive patients * No other concurrent investigational agents * No concurrent sargramostim (GM-CSF) NOTE: \*Insertion of a vascular device is not considered major or minor surgery

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

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Bevacizumab; Capecitabine; Irinotecan; Oxaliplatin

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Camptothecin; Alkaloids; Coordination Complexes; Organic Chemicals

Study Officials

• Smitha Krishnamurthi, MD

  Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2006
• First Posted: February 24, 2006
• Study Start: March 1, 2006
• Primary Completion: October 1, 2009
• Study Completion: May 1, 2011
• Last Updated: January 16, 2012

Record last verified: 2012-01

Locations

US (1)