Safety of ON 01910.Na and Irinotecan or ON 01910.Na and Oxaliplatin in Patients With Hepatoma

June 22, 2017 updated by: Onconova Therapeutics, Inc.

A Phase 1 Dose-Escalation Study of the Safety and Clinical Effects of ON 01910.Na in Combination With Either Irinotecan or Oxaliplatin in Patients With Hepatoma and Other Advanced Solid Tumors

Studies done in the laboratory have demonstrated beneficial effects of ON 01910.Na, a new, unapproved drug, when it is used in combination either irinotecan and oxaliplatin, two approved, extensively used anti-cancer drugs. In these laboratory studies, mice implanted with cells (Bel-7402 cells) that came from a human tumor were used as a model of liver cancer. In mice that were not treated, the Bel-7402 cells formed very large tumors. In mice that were treated with ON 01910.Na, irinotecan or oxaliplatin alone, growth of tumors was reduced compared to the untreated group. When a combination of ON 01910.Na and irinotecan or of ON 01910.Na and oxaliplatin was used to treat the mice, tumor growth was completely inhibited. Another observation in these studies was that toxicity did not increase when the combinations were used. These results and similar results from other studies support the hypothesis that a combination of ON 01910.Na and irinotecan or of ON 01910.Na and oxaliplatin would be an effective and tolerable treatment for liver and other types of cancer.

The primary objective of this phase 1 study is to find out what doses of ON 01910.Na in combination with either irinotecan or oxaliplatin are safe and tolerable in patients with liver and other types of cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is an open-label, 2-arm, dose-escalation combination-therapy study in which patients with hepatoma and other advanced malignancies will be assigned by the Investigator to dosing with either irinotecan plus ON 01910.Na (Group A), or oxaliplatin plus ON 01910.Na (Group B). Note: As of Amendment 2 of this protocol, treatment in the irinotecan arm of the study (Group A) is closed to enrollment and patients will be enrolled only in Group B, the oxaliplatin treatment arm. Patients will be enrolled in 1 of 4 Cohorts (4 sequential Cohorts in Group B) of 3 patients each. Up to 6 additional patients will be tested at the MTD.

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10029
        • Mount Sinai Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male and female patients ≥18 years of age with histologically or cytologically confirmed hepatoma and other solid tumors that are metastatic or progressive, for whom no standard therapy holds curative potential and for whom irinotecan or oxaliplatin are reasonable treatment options.
  • Patients must have evaluable disease, either measurable on imaging or with informative tumor marker(s).
  • Eastern Collaborative Oncology Group (ECOG) Performance Status of ≤2.
  • Life expectancy >12 weeks.
  • Any acute or chronic adverse effects of prior chemotherapy have resolved to <Grade 2 as determined by CTCAE v3 criteria.
  • Existing or planned central venous access with a 2-channel infusion catheter system.
  • Laboratory values meet the following criteria: Absolute neutrophil count ≥1,500 cells/µL; Platelets ≥100,000 cells/µL; Total bilirubin ≤1.5 times the upper limit of normal; AST (SGOT) ≤2.5 times the upper limit of normal; ALT (SGPT) ≤2.5 times the upper limit of normal; Serum creatinine ≤1.5 mg/dL or a measured creatinine clearance ≥50 mL/min; Negative βhCG test in women of childbearing potential (defined as women ≤50 years of age or history of amenorrhea for ≤12 months prior to study entry).
  • Patients with primary liver cancer or hepatic metastasis are eligible to enroll, provided they meet the following: Total bilirubin is ≤2 mg/dL; AST and ALT are each ≤5 times the institutional upper limit of normal; Ascites, if present, is manageable with diuretic agents alone.
  • If there is a history of treated brain metastases, these must have been clinically stable for ≥4 weeks prior to enrollment.

Exclusion Criteria:

  • Women who are pregnant or lactating.
  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
  • Severe liver dysfunction (Child-Pugh Class C or uncompensated Class B with persistent encephalopathy, persistent ascites, or prothrombin time >1.5 times the upper limit of normal) is present.
  • Patients with a history of esophageal bleeding are excluded unless arices have been sclerosed or banded and bleeding episodes have not occurred during the prior 6 months.
  • Contraindications, including known hypersensitivity, to the assigned chemotherapy agent (i.e., irinotecan or oxaliplatin).
  • Prior receipt of ON 01910.Na or prior participation in this protocol.
  • Use of any investigational agents within 4 weeks of study enrollment.
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements, as determined by the Investigator.
  • Patients with ascites requiring active medical management including paracentesis, peripheral bilateral edema or hyponatremia (defined as serum sodium value of <134 Meq/L).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group A - irinotecan

Note: As of Amendment 2 (March 2009), treatment in the irinotecan arm of the study (Group A) is closed to enrollment.

Treatment with escalating doses of ON 01910.Na in combination with irinotecan.
Drug: irinotecan and ON 01910.Na

ON 01910.Na will be administered by IV infusion over 24 hours once per week in a 6-week cycle (6 doses per cycle). The dose of ON 01910.Na will start at 250 mg/m2 and will proceed to higher levels based on safety of the combination regimen in the previous cohort.

Irinotecan 180 mg/m2 will initially be administered by IV infusion over 90 minutes q2 weeks of a 6-week cycle (3 doses per cycle). Dose modifications due to toxicity will be instituted according to approved labelling.

Other Names:
  • Camptosar
  • rigosertib sodium
  • CPT-11
  • camptothecin-11
  • diaminocyclohexane oxalatoplatinum
  • irinotecan HCl
Experimental: Group B - oxaliplatin
Treatment with escalating doses of ON 01910.Na in combination with oxaliplatin.
Drug: oxaliplatin and ON 01910.Na

ON 01910.Na will be administered by IV infusion over 24 hours once per week in a 6-week cycle (6 doses per cycle). The dose of ON 01910.Na will start at 250 mg/m2 and will proceed to higher levels based on safety of the combination regimen in the previous cohort.

Oxaliplatin 85 mg/m2 will initially be administered by IV infusion over 120 minutes every 2 weeks of a 6-week cycle (3 doses per cycle). Dose modifications due to toxicity will be instituted according to approved labeling.

Other Names:
  • Eloxatin
  • rigosertib sodium
  • oxalatoplatin
  • oxaloplatinum

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
maximum tolerated dose
Time Frame: 6 - 12 months
6 - 12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
pharmacokinetics
Time Frame: 6 - 12 months
6 - 12 months
tumor measurement
Time Frame: 6 - 12 months
6 - 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Onconova Therapeutics, Inc.

Investigators

  • Principal Investigator: Takao Ohnuma, M.D., Icahn School of Medicine at Mount Sinai

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2008

Primary Completion (Actual)

July 1, 2011

Study Completion (Actual)

July 1, 2011

Study Registration Dates

First Submitted

March 12, 2009

First Submitted That Met QC Criteria

March 12, 2009

First Posted (Estimate)

March 13, 2009

Study Record Updates

Last Update Posted (Actual)

June 23, 2017

Last Update Submitted That Met QC Criteria

June 22, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Onconova 04-08

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Advanced Solid Tumor

Clinical Trials on irinotecan and ON 01910.Na

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Morocco

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe