A Study of Picoplatin in Colorectal Cancer

NCT00478946 | Unknown Phase 1

• 1 other identifier: 0501
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 16

Brief Summary

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.

Conditions

Colorectal Cancer

Keywords

colorectal cancer; picoplatin; FOLFOX; FOLPI; chemotherapy

Outcome Measures

Primary Outcomes (2)

• dose-limiting toxicity

  within the first four weeks of treatment

• maximum tolerated dose

  within the first two cycles of treatment

Secondary Outcomes (1)

• safety and efficacy

  duration of the study

Study Arms (2)

1

EXPERIMENTAL

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; Drug: FOLPI

2

ACTIVE COMPARATOR

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

Interventions

(FOLPI) Picoplatin with 5-FU and Leucovorin DRUG

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.

1

FOLPI DRUG

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.

1

FOLFOX DRUG

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.

2

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Poniard Pharmaceuticals: lead

Study Sites (16)

Leningrad Regional Oncology Center, Chemotherapy Department - Phase 2

Kuzmolovsky Village, Vsevolozhsk, 188663, Russia

Location

Regional Oncology Center - Phase 2

Astrakhan, 414041, Russia

Location

Chelyabinsk Regional Oncology Center - Phase 1

Chelyabinsk, 454087, Russia

Location

Regional Oncology Center, Chemotherapy Department - Phase 2

Engel's, 413115, Russia

Location

Kazan Oncology Center

Kazan', 420111, Russia

Location

Blokhin Russian Oncology Research Center - Phase 1

Moscow, 115478, Russia

Location

Semashko Central Clinical Hospital #2 - Phase 1

Moscow, 129128, Russia

Location

Medical Radiology Research Center of Russian Academy of Medical Sciences- Phase 1

Obninsk, 249036, Russia

Location

Republic Oncology Center of the Ministry of Healthcare of Karelia Republic - Phase 2

Petrozavodsk, 185007, Russia

Location

Rostov Research Institute of Oncology- Phase 2

Rostov-na-Dony, 350086, Russia

Location

St. Petersburg Academy of Postgraduate Education - Phase 2

Saint Petersburg, 194291, Russia

Location

St. Petersburg Mechnikov State Medical Academy - Phase 2

Saint Petersburg, 195067, Russia

Location

St. Petersburg City Oncology Center - Phase 1

Saint Petersburg, 198255, Russia

Location

Regional Clinical Oncology Center - Phase 2

Ulyanovsk, 432063, Russia

Location

Voronezh Regional Clinical Oncology Center - Phase 2

Voronezh, 394000, Russia

Location

Yaroslavl Regional Oncology Center - Phase 1

Yaroslavl, 150054, Russia

Location

Related Publications (9)

• Douillard JY, Schiller J. ZD0473 combined with other chemotherapeutic agents for the treatment of solid malignancies. Eur J Cancer. 2002 Dec;38 Suppl 8:S25-31. doi: 10.1016/s0959-8049(02)80020-x.

  PMID: 12645909 BACKGROUND

• Beale P, Judson I, O'Donnell A, Trigo J, Rees C, Raynaud F, Turner A, Simmons L, Etterley L. A Phase I clinical and pharmacological study of cis-diamminedichloro(2-methylpyridine) platinum II (AMD473). Br J Cancer. 2003 Apr 7;88(7):1128-34. doi: 10.1038/sj.bjc.6600854.

  PMID: 12671715 BACKGROUND

• Raynaud FI, Boxall FE, Goddard PM, Valenti M, Jones M, Murrer BA, Abrams M, Kelland LR. cis-Amminedichloro(2-methylpyridine) platinum(II) (AMD473), a novel sterically hindered platinum complex: in vivo activity, toxicology, and pharmacokinetics in mice. Clin Cancer Res. 1997 Nov;3(11):2063-74.

  PMID: 9815598 BACKGROUND

• Holford J, Raynaud F, Murrer BA, Grimaldi K, Hartley JA, Abrams M, Kelland LR. Chemical, biochemical and pharmacological activity of the novel sterically hindered platinum co-ordination complex, cis-[amminedichloro(2-methylpyridine)] platinum(II) (AMD473). Anticancer Drug Des. 1998 Jan;13(1):1-18.

  PMID: 9474239 BACKGROUND

• Holford J, Sharp SY, Murrer BA, Abrams M, Kelland LR. In vitro circumvention of cisplatin resistance by the novel sterically hindered platinum complex AMD473. Br J Cancer. 1998;77(3):366-73. doi: 10.1038/bjc.1998.59.

  PMID: 9472630 BACKGROUND

• Rogers P, Boxall FE, Allott CP, Stephens TC, Kelland LR. Sequence-dependent synergism between the new generation platinum agent ZD0473 and paclitaxel in cisplatin-sensitive and -resistant human ovarian carcinoma cell lines. Eur J Cancer. 2002 Aug;38(12):1653-60. doi: 10.1016/s0959-8049(02)00107-7.

  PMID: 12142057 BACKGROUND

• Sharp SY, O'Neill CF, Rogers P, Boxall FE, Kelland LR. Retention of activity by the new generation platinum agent AMD0473 in four human tumour cell lines possessing acquired resistance to oxaliplatin. Eur J Cancer. 2002 Nov;38(17):2309-15. doi: 10.1016/s0959-8049(02)00244-7.

  PMID: 12441268 BACKGROUND

• Plasencia C, Abad A, Martinez-Balibrea E, Taron M. Antiproliferative effects of ZD0473 (AMD473) in combination with 5-fluorouracil or SN38 in human colorectal cancer cell lines. Invest New Drugs. 2004 Nov;22(4):399-409. doi: 10.1023/B:DRUG.0000036682.99818.71.

  PMID: 15292710 BACKGROUND

• Murakami H, Tamura T, Yamada Y, Yamamoto N, Ueda Y, Shimoyama T, Saijo N. ZD0473 pharmacokinetics in Japanese patients: a Phase I dose-escalation study. Eur J Cancer. 2002 Dec;38 Suppl 8:S1-5. doi: 10.1016/s0959-8049(02)80012-0.

  PMID: 12645906 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

amminedichloro(2-methylpyridine)platinum(II); Fluorouracil; Leucovorin; Folfox protocol

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)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Robert Earhart, MD, PhD

  Poniard Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: May 23, 2007
• First Posted: May 25, 2007
• Study Start: April 1, 2006
• Primary Completion: December 1, 2009
• Study Completion: June 1, 2010
• Last Updated: January 21, 2009

Record last verified: 2009-01

Locations

RU (16)