A Phase II Study of Ziv-aflibercept in Combination With Capecitabine/Oxaliplatin (XELOX) Chemotherapy in the Front-Line Treatment of Patients With Metastatic Colorectal Cancer

NCT02079220 | Withdrawn Phase 2 DMC

• 1 other identifier: 13-145
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, two-arm, phase II trial to evaluate the anti-tumor activity, safety, and tolerability of ziv-aflibercept in combination with XELOX chemotherapy in the first-line treatment of subjects with mCRC. Two different schedules of ziv-aflibercept in combination with XELOX will be evaluated in this study: every 2 week schedule (Arm A) and the every 3 week schedule (Arm B). The choice between arm A and arm B will depend on the investigator's preference. Arm A (every 2 week schedule) Dosage and dosage regimen for all study periods

• Capecitabine: will be administered 1,000 mg/m2 orally twice a day on Days 1 - 7 of each cycle, repeating every 14 days.
• Oxaliplatin: will be administered 85 mg/m2 IV on Day 1 of each cycle, repeating every 14 days.
• Ziv-aflibercept: will be administered 4 mg/kg IV on Day 1 of each cycle, repeating every 14 days. Arm B (every 3 week schedule): Dosage and dosage regimen for all study periods
• Capecitabine: will be administered 850 mg/m2 orally twice a day on Days 1 - 14 of each cycle, repeating every 21 days.
• Oxaliplatin: will be administered 130 mg/m2 IV on Day 1 of each cycle, repeating every 21 days.
• Ziv-aflibercept: will be administered 6 mg/kg IV on Day 1 of each cycle, repeating every 21 days.

Conditions

Metastatic Colorectal Cancer

Keywords

Colorectal Cancer; Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• anti-tumor activity of ziv-aflibercept in combination with XELOX in the first-line treatment of patients with metastatic colorectal cancer (mCRC)

  up to 6 years

Secondary Outcomes (1)

• Progression-free survival (PFS)

  Up to 6 years

Study Arms (2)

Arm A

EXPERIMENTAL

Arm A (every 2 week schedule) Dosage and dosage regimen for all study periods * Capecitabine: will be administered 1,000 mg/m2 orally twice a day on Days 1 - 7 of each cycle, repeating every 14 days. * Oxaliplatin: will be administered 85 mg/m2 IV on Day 1 of each cycle, repeating every 14 days. * Ziv-aflibercept: will be administered 4 mg/kg IV on Day 1 of each cycle, repeating every 14 days.

Drug: Arm A

Arm B

EXPERIMENTAL

Arm B (every 3 week schedule): Dosage and dosage regimen for all study periods * Capecitabine: will be administered 850 mg/m2 orally twice a day on Days 1 - 14 of each cycle, repeating every 21 days. * Oxaliplatin: will be administered 130 mg/m2 IV on Day 1 of each cycle, repeating every 21 days. * Ziv-aflibercept: will be administered 6 mg/kg IV on Day 1 of each cycle, repeating every 21 days.

Drug: Arm B

Interventions

Arm A DRUG

* Capecitabine * Oxaliplatin * Ziv-aflibercept

Also known as: Xeloda, ELOXATIN, ZALTRAP

Arm A

Arm B DRUG

Capecitabine Oxaliplatin Ziv-aflibercept

Also known as: Xeloda, ELOXATIN, ZALTRAP

Arm B

Eligibility Criteria

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

You may qualify if:

• The study will be limited to subjects with newly diagnosed mCRC without any prior systemic chemotherapy for metastatic disease.
• The diagnosis of metastatic colorectal cancer will be based on histologic or cytologic confirmation.
• Subjects must have the ability to swallow oral medication.
• Subjects must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan, MRI, or calipers by clinical exam.
• Any prior chemotherapy for mCRC is not allowed. Adjuvant chemotherapy with oxaliplatin-containing regimen CRC within the last 12 months is not allowed. Adjuvant chemotherapy with Fluorouracil (5-FU) or capecitabine alone within the last 6 months is allowed.
• Age ≥ 18 years.
• Both men and women of all races and ethnic groups are eligible for this trial.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 (Karnofsky ≥ 60%).
• Life expectancy of greater than 12 months.
• Patients must have normal organ and marrow function as defined below:
• Absolute Neutrophil Count ≥ 1,500/mm3
• Platelets ≥ 100,000/mm3
• Total Bilirubin 2 × institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and Alanine transaminase (ALT) 2.5 × institutional upper limit of normal (AST and ALT ≤ 5.0 x ULN is acceptable if liver has tumor involvement).
• Creatinine Clearance (CrCl) 30 mL/min.

You may not qualify if:

• Unwilling or unable to follow protocol requirements or to give informed consent.
• Any prior chemotherapy for mCRC.
• Adjuvant chemotherapy with oxaliplatin-containing regimen CRC within the last 12 months.
• Adjuvant chemotherapy with 5-FU or capecitabine alone within the last 6 months is allowed.
• CrCl \< 30 mL/min
• Any peripheral neuropathy of grade ≥ 2
• Patients with known dihydropyrimidine dehydrogenase (DPD) deficiency
• Patients with urine protein creatinine ration \> 1 or urine protein \> 500 mg/24 hours.
• Patients who have had radiotherapy within 4 weeks to entering the study or those who have not recovered from adverse events due to radiotherapy administered more than 4 weeks earlier.
• Patients with uncontrolled or symptomatic brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Presence of metastatic disease that, in the opinion of the investigator, would require palliative treatment within 4 weeks of enrollment.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because ziv-aflibercept, capecitabine, and oxaliplatin are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ziv-aflibercept, capecitabine, and oxaliplatin, breastfeeding should be discontinued if the mother is treated with ziv-aflibercept, capecitabine, and oxaliplatin.
• HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ziv-aflibercept, capecitabine, and oxaliplatin. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
• Malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, resection of the stomach or small bowel, or other disease or condition significantly affecting gastrointestinal function.

Sponsors & Collaborators

• James J Lee: lead
• Sanofi: collaborator

Study Sites (1)

Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Capecitabine; Oxaliplatin; aflibercept

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)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Study Design

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

Study Record Dates

• First Submitted: March 3, 2014
• First Posted: March 5, 2014
• Study Start: March 1, 2014
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2018
• Last Updated: July 31, 2017

Record last verified: 2017-07

Locations

US (1)