A Study of Picoplatin in Colorectal Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2009 by Poniard Pharmaceuticals.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Poniard Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00478946
First received: May 23, 2007
Last updated: January 20, 2009
Last verified: January 2009
  Purpose

Colorectal cancer is a type of cancer that begins in the large intestine (colon) or the rectum (end of the colon). Several drugs are often given in combination to treat colorectal cancer. One of the most active treatment combinations is known as FOLFOX, which is a combination of 5-fluorouracil (5-FU), leucovorin, and oxaliplatin. Oxaliplatin is a type of platinum drug and was approved by the FDA in 2004. While generally well-tolerated, oxaliplatin may cause toxicity to the nerves, such as sensory loss or cold sensitivity.

Picoplatin is a new type of platinum drug that has shown activity with 5-FU in pre-clinical studies and has undergone extensive Phase 1 and Phase 2 testing in a variety of cancers. No significant nerve toxicity has been seen in previous studies of picoplatin.

This study will review the safety and effectiveness of FOLPI, which is the combination of 5-FU and leucovorin with picoplatin in participants with colorectal cancer.


Condition Intervention Phase
Colorectal Cancer
Drug: (FOLPI) Picoplatin with 5-FU and Leucovorin
Drug: FOLPI
Drug: FOLFOX
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Open-Label Study of Picoplatin in Combination With 5-Fluorouracil and Leucovorin as Initial Therapy in Subjects With Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Poniard Pharmaceuticals:

Primary Outcome Measures:
  • dose-limiting toxicity [ Time Frame: within the first four weeks of treatment ] [ Designated as safety issue: Yes ]
  • maximum tolerated dose [ Time Frame: within the first two cycles of treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • safety and efficacy [ Time Frame: duration of the study ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 43
Study Start Date: April 2006
Estimated Study Completion Date: June 2010
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Picoplatin, 150 mg/m2, 5-FU and leucovorin (q 4 weeks, Schedule B). Leucovorin, 400 mg/m2 in D5W and leucovorin (± picoplatin) will be followed by a 5-FU bolus of 400 mg/m2 and then by 5-FU, 2,400 mg/m2 in D5W administered as a 46-hour continuous infusion.
Drug: (FOLPI) Picoplatin with 5-FU and Leucovorin
Picoplatin, 150 mg/m2, 5-FU and leucovorin (q 4 weeks, Schedule B). Leucovorin, 400 mg/m2 in D5W and leucovorin (± picoplatin) will be followed by a 5-FU bolus of 400 mg/m2 and then by 5-FU, 2,400 mg/m2 in D5W administered as a 46-hour continuous infusion.
Drug: FOLPI
Picoplatin, 150 mg/m2 to be administered with every alternate cycle of 5-FU and leucovorin (q 4 weeks, Schedule B). Leucovorin, 400 mg/m2 in D5W, will be administered as a 2-hour infusion, either alone or, if the patient is to receive picoplatin that cycle, at the same time as picoplatin, in separate bags using a Y-line. The leucovorin (± picoplatin) will be followed by a 5-FU bolus of 400 mg/m2 and then by 5-FU, 2,400 mg/m2 in D5W administered as a 46-hour continuous infusion.
Active Comparator: 2
FOLFOX Oxaliplatin 85 mg/m2, as a 2-hour infusion Leucovorin (400 mg/m2 in D5W) and Oxaliplatin. Leucovorin + oxaliplatin will be followed by a 5-FU bolus of 400 mg/m2 and then by 5-FU, 2400 mg/m2 in D5W administered as a 46-hour continuous infusion.
Drug: FOLFOX
Oxaliplatin 85 mg/m. Leucovorin (400 mg/m2 in D5W). Oxaliplatin and leucovorin Leucovorin + oxaliplatin 5-FU bolus of 400 mg/m2 and then by 5-FU, 2400 mg/m2 in D5W administered as a 46-hour continuous infusion.

Detailed Description:

Subjects will be randomized centrally to treatment with picoplatin administered either every two or every four weeks and will be assigned a dose of picoplatin dependent on the study results to date. Each patient will also receive therapy every two weeks with 5-FU and leucovorin. In each schedule, the cohort size will be 3 subjects, to be expanded to 6 subjects if a dose-limiting toxicity is observed. If not dose-limiting toxicity observed among the 3 subjects within a cohort, picoplatin dose escalation may proceed, until the maximum tolerated dose is established.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed adenocarcinoma of the colon or rectum.
  • Metastatic disease consistent with colorectal adenocarcinoma. Stage M1, and not amenable to curative surgery. Subjects with only locally persistent or only locally recurrent disease are not eligible.
  • No prior systemic therapy for metastatic cancer. Prior adjuvant chemotherapy with a 5-FU-based treatment regimen not containing oxaliplatin or irinotecan is acceptable after a treatment-free interval of at least 6 months.
  • ECOG performance score (PS) of 0 or 1.
  • Life expectancy more than 3 months.
  • Subject must have measurable disease, defined by the RECIST criteria.
  • At least 28 days must have elapsed since prior surgery except venous access device placement.
  • At least 28 days must have elapsed since prior radiotherapy.
  • At least 28 days must have elapsed since a prior investigational agent.
  • Absolute neutrophil count (ANC) equal to or greater than 1.5 x 10^9/L.
  • Platelet count equal to or greater than 100 x 10^9/L.
  • Hemoglobin equal or greater than 10g/dL (must be obtained at least 3 days after any transfusion).
  • Serum AST and ALT levels less than or equal to 2.5 times upper limit of normal (ULN) or less than 5 times ULN if liver involvement is present.
  • Serum bilirubin of less than or equal to 1.5 ULN.
  • Serum creatinine of less than or equal to ULN.
  • Women of childbearing potential must have a negative pregnancy test (serum or urine beta HCG).
  • All subjects must agree to use appropriate birth control methods while on study and for 1 month after completion of study chemotherapy.

Exclusion Criteria:

  • Concurrent use of EGFR inhibitors or anti-VEGF agents.
  • No clinically significant obstructive symptoms or intestinal bleeding.
  • Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom (e.g. Crohn's disease, ulcerative colitis, malabsorption syndrome, Grade 2+ diarrhea of any etiology at baseline).
  • History of serious cardiac disease, defined as myocardial infarction within six months of enrollment, congestive heart failure classified by the New York Heart Association as class III or IV, uncontrolled cardiac arrhythmias, poorly controlled or unstable angina, or electrocardiographic evidence of acute ischemia.
  • Clinical evidence of brain metastases or central nervous system disease.
  • Symptomatic peripheral neuropathy (equivalent to Grade 2 or higher CTCAE toxicity criteria).
  • Uncontrolled intercurrent illness (e.g. active infection).
  • Pregnant or nursing.
  • Serious medical or psychiatric illness that could potentially interfere with the completion of study treatment according to this protocol.
  • Malignancy other than colorectal carcinoma within the past 5 years, except, curatively treated, superficial skin cancer or carcinoma in situ of the cervix or breast.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00478946

Locations
Russian Federation
Leningrad Regional Oncology Center, Chemotherapy Department - Phase 2
Kuzmolovsky Village, Vsevolozhsk, Russian Federation, 188663
Regional Oncology Center - Phase 2
Astrakhan, Russian Federation, 414041
Chelyabinsk Regional Oncology Center - Phase 1
Chelyabinsk, Russian Federation, 454087
Regional Oncology Center, Chemotherapy Department - Phase 2
Engels, Russian Federation, 413115
Kazan Oncology Center
Kazan, Russian Federation, 420111
Semashko Central Clinical Hospital #2 - Phase 1
Moscow, Russian Federation, 129128
Blokhin Russian Oncology Research Center - Phase 1
Moscow, Russian Federation, 115478
Medical Radiology Research Center of Russian Academy of Medical Sciences- Phase 1
Obninsk, Russian Federation, 249036
Republic Oncology Center of the Ministry of Healthcare of Karelia Republic - Phase 2
Petrozavodsk, Russian Federation, 185007
Rostov Research Institute of Oncology- Phase 2
Rostov-na-Dony, Russian Federation, 350086
St. Petersburg City Oncology Center - Phase 1
St. Petersburg, Russian Federation, 198255
St. Petersburg Academy of Postgraduate Education - Phase 2
St. Petersburg, Russian Federation, 194291
St. Petersburg Mechnikov State Medical Academy - Phase 2
St. Petersburg, Russian Federation, 195067
Regional Clinical Oncology Center - Phase 2
Ulyanovsk, Russian Federation, 432063
Voronezh Regional Clinical Oncology Center - Phase 2
Voronezh, Russian Federation, 394000
Yaroslavl Regional Oncology Center - Phase 1
Yaroslavl, Russian Federation, 150054
Sponsors and Collaborators
Poniard Pharmaceuticals
Investigators
Study Director: Robert Earhart, MD, PhD Poniard Pharmaceuticals
  More Information

Publications:

Responsible Party: Robert Earhart, MD, PhD, Poniard Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00478946     History of Changes
Other Study ID Numbers: 0501
Study First Received: May 23, 2007
Last Updated: January 20, 2009
Health Authority: Russia: Pharmacological Committee, Ministry of Health
United States: Food and Drug Administration

Keywords provided by Poniard Pharmaceuticals:
colorectal cancer
picoplatin
FOLFOX
FOLPI
chemotherapy

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on September 18, 2014