Advanced Solid TumorsPhase 1NCT00861328

Safety Study of ON 01910.Na in Combination With Irinotecan or Oxaliplatin

A Phase 1 study testing ON 01910.Na and irinotecan and ON 01910.Na and oxaliplatin in people with Advanced Solid Tumors, run by Traws Pharma, Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Advanced Solid Tumors
What is being tested?: ON 01910.Na and irinotecan and ON 01910.Na and oxaliplatin
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: 1 siteUnited States
Study dates: Feb 2008to Jul 2011
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male and female patients ≥18 years of age with histologically or cytologically confirmed 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.

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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.
UGT1A1 genotype of patient must be known or a UGT1A1 genotype test must be done for patients being considered for treatment in Group A.

Who cannot join

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 varices 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.

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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 who are homozygous for the UGT1A1*28 allele will be excluded from participating in Group A of this protocol.
Patients with ascites requiring active medical management including paracentesis, peripheral bilateral edema or hyponatremia (defined as serum sodium value of <134 Meq/L).

Trial locations and contacts

1 site in 1 country.

United States1 site

Albert Einstein Cancer Center
The Bronx, New York, 10461

Other trials in United States

About this study

Official title: 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 Advanced Solid Tumors

Treatment of cancer is often improved if two or more drugs are used in combination. In animal studies, the use of the combination of ON 01910.Na (a new, unapproved drug) and irinotecan or oxaliplatin (two approved and extensively used anti-cancer drugs) gave better results against tumor cells than the use of any of the single drugs alone. In addition, the use of the combinations did not result in an increase of side effects. This clinical trial will determine what is the highest dose of ON 01910.Na that can be given safely in combination with either irinotecan or oxaliplatin in human patients.

Read the detailed description

This is an open-label, 2-arm, dose-escalation combination-therapy study in which patients with 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). The Investigator will make this assignment using clinical judgment, taking into consideration the patient's tumor type, UGT1A1 genotype when applicable (i.e., patients considered for treatment in Group A will be tested for UGT1A1 genotype, if not already known, and patients homozygous for the UGT1A1*28 allele will be excluded from Group A), prior treatment, and current clinical condition. Patients will be enrolled in 1 of 8 Cohorts (4 sequential Cohorts in Group A and 4 in Group B) of 3 patients each. Up to 6 additional patients will be tested at the MTD. Groups A and B will enroll and proceed simultaneously.

Conditions: Advanced Solid Tumors
Being tested: ON 01910.Na and irinotecan, ON 01910.Na and oxaliplatin
Keywords: Phase 1, maximum tolerated dose, oxaliplatin, irinotecan, ON 01910.Na

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ON 01910.Na and irinotecanDrug
Also called Campostar, camptothecin-11, irinotecan, irinotecan HCl
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 dose levels after safety evaluation.
The suggested starting dose of Irinotecan is 180 mg/m2 administered by intravenous (IV) infusion over 90 minutes every 2 weeks of a 6-week cycle (3 doses per cycle). Reductions in the starting doses according to recommendations of current approved prescribing information may be considered after review of patients' medical histories and potential tolerances to treatment with the chemotherapy agent.
ON 01910.Na and oxaliplatinDrug
Also called diaminocyclohexane oxalatoplatinum, oxalatoplatin, oxalatoplatinum, Eloxatin
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 dose levels after safety review of the combination regimen in the previous cohort.
The suggested starting dose of Oxaliplatin is 85 mg/m2 administered by IV infusion over 120 minutes every 2 weeks of a 6-week cycle (3 doses per cycle). Reductions in the starting doses according to recommendations of current approved prescribing information may be considered after review of patients' medical histories and potential tolerances to treatment with the chemotherapy agent.

Study groups in NCT00861328
Study group	Role	What they receive
A	Experimental	Treatment of escalating doses of ON 01910.Na in combination with irinotecan Receives: Drug: ON 01910.Na and irinotecan
B	Experimental	Treatment of escalating doses of ON 01910.Na in combination with oxaliplatin Receives: Drug: ON 01910.Na and oxaliplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

maximum tolerated dose
Measured: 1 - 3 months

Secondary outcomes (3)

Pharmacokinetic parameters
Measured: 1 month
tumor measurements
Measured: 1 - 3 months
tumor markers
Measured: 1 - 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2008Jul 2011

First posted13 Mar 2009 (estimated)
Study startFeb 2008
Primary completionJul 2011
Study completionJul 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (5)Papers the sponsor has linked to this study.
Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00861328
Sponsor's protocol ID: Onconova 04-06
Status last verified: Jun 2017
First submitted: 12 Mar 2009
Last updated: 23 Jun 2017
Results posted: No
Data monitoring committee: No

Publications

Jimeno A, Chan A, Cusatis G, Zhang X, Wheelhouse J, Solomon A, Chan F, Zhao M, Cosenza SC, Ramana Reddy MV, Rudek MA, Kulesza P, Donehower RC, Reddy EP, Hidalgo M. Evaluation of the novel mitotic modulator ON 01910.Na in pancreatic cancer and preclinical development of an ex vivo predictive assay. Oncogene. 2009 Jan 29;28(4):610-8. doi: 10.1038/onc.2008.424. Epub 2008 Nov 24.
PubMed 19029951
Jimeno A, Li J, Messersmith WA, Laheru D, Rudek MA, Maniar M, Hidalgo M, Baker SD, Donehower RC. Phase I study of ON 01910.Na, a novel modulator of the Polo-like kinase 1 pathway, in adult patients with solid tumors. J Clin Oncol. 2008 Dec 1;26(34):5504-10. doi: 10.1200/JCO.2008.17.9788. Epub 2008 Oct 27.
PubMed 18955447
Reddy MV, Mallireddigari MR, Cosenza SC, Pallela VR, Iqbal NM, Robell KA, Kang AD, Reddy EP. Design, synthesis, and biological evaluation of (E)-styrylbenzylsulfones as novel anticancer agents. J Med Chem. 2008 Jan 10;51(1):86-100. doi: 10.1021/jm701077b. Epub 2007 Dec 19.
PubMed 18088089
Gumireddy K, Reddy MV, Cosenza SC, Boominathan R, Baker SJ, Papathi N, Jiang J, Holland J, Reddy EP. ON01910, a non-ATP-competitive small molecule inhibitor of Plk1, is a potent anticancer agent. Cancer Cell. 2005 Mar;7(3):275-86. doi: 10.1016/j.ccr.2005.02.009.
PubMed 15766665
Garcia-Manero G, Fenaux P. Comprehensive Analysis of Safety: Rigosertib in 557 Patients with Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML). Blood Dec 2016, 128 (22) 2011; ASH 2016.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
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A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
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A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
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Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
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RecruitingPhase 1/2
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Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma

All Advanced Solid Tumors trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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 Advanced Solid Tumors
ClinicalTrials.gov ID: NCT00861328
Acronym / sponsor ID: Onconova 04-06
Conditions: Advanced Solid Tumors
Keywords: Phase 1, maximum tolerated dose, oxaliplatin, irinotecan, ON 01910.Na
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 18 participants (actual)
Lead sponsor: Traws Pharma, Inc.Industry (pharma, biotech, devices)
Study start: Feb 2008
Primary completion: Jul 2011 (actual)
Study completion: Jul 2011 (actual)
First posted: 13 Mar 2009 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
A	Experimental	Drug: ON 01910.Na and irinotecanTreatment of escalating doses of ON 01910.Na in combination with irinotecan
B	Experimental	Drug: ON 01910.Na and oxaliplatinTreatment of escalating doses of ON 01910.Na in combination with oxaliplatin

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

Male and female patients ≥18 years of age with histologically or cytologically confirmed 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.

Key exclusion criteria (10 listed)

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 varices 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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ON 01910.Na and irinotecanAlso: Campostar, camptothecin-11, irinotecan, irinotecan HClON 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 dose levels after safety evaluation. The suggested starting dose of Irinotecan is 180 mg/m2 administered by intravenous (IV) infusion over 90 minutes every 2 weeks of a 6-week cycle (3 doses per cycle). Reductions in the starting doses according to recommendations of current approved prescribing information may be considered after review of patients' medical histories and potential tolerances to treatment with the chemotherapy agent.	Drug	A
ON 01910.Na and oxaliplatinAlso: diaminocyclohexane oxalatoplatinum, oxalatoplatin, oxalatoplatinum, EloxatinON 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 dose levels after safety review of the combination regimen in the previous cohort. The suggested starting dose of Oxaliplatin is 85 mg/m2 administered by IV infusion over 120 minutes every 2 weeks of a 6-week cycle (3 doses per cycle). Reductions in the starting doses according to recommendations of current approved prescribing information may be considered after review of patients' medical histories and potential tolerances to treatment with the chemotherapy agent.	Drug	B

Primary outcome

maximum tolerated dose
Time frame: 1 - 3 months

3 secondary outcomes

Pharmacokinetic parameters
Time frame: 1 month
tumor measurements
Time frame: 1 - 3 months
tumor markers
Time frame: 1 - 3 months

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2017.
Background: PubMed 19029951Jimeno A, Chan A, Cusatis G, Zhang X, Wheelhouse J, Solomon A, Chan F, Zhao M, Cosenza SC, Ramana Reddy MV, Rudek MA, Kulesza P, Donehower RC, Reddy EP, Hidalgo M. Evaluation of the novel mitotic modulator ON 01910.Na in pancreatic cancer and preclinical development of an ex vivo predictive assay. Oncogene. 2009 Jan 29;28(4):610-8. doi: 10.1038/onc.2008.424. Epub 2008 Nov 24.
Background: PubMed 18955447Jimeno A, Li J, Messersmith WA, Laheru D, Rudek MA, Maniar M, Hidalgo M, Baker SD, Donehower RC. Phase I study of ON 01910.Na, a novel modulator of the Polo-like kinase 1 pathway, in adult patients with solid tumors. J Clin Oncol. 2008 Dec 1;26(34):5504-10. doi: 10.1200/JCO.2008.17.9788. Epub 2008 Oct 27.
Background: PubMed 18088089Reddy MV, Mallireddigari MR, Cosenza SC, Pallela VR, Iqbal NM, Robell KA, Kang AD, Reddy EP. Design, synthesis, and biological evaluation of (E)-styrylbenzylsulfones as novel anticancer agents. J Med Chem. 2008 Jan 10;51(1):86-100. doi: 10.1021/jm701077b. Epub 2007 Dec 19.
Background: PubMed 15766665Gumireddy K, Reddy MV, Cosenza SC, Boominathan R, Baker SJ, Papathi N, Jiang J, Holland J, Reddy EP. ON01910, a non-ATP-competitive small molecule inhibitor of Plk1, is a potent anticancer agent. Cancer Cell. 2005 Mar;7(3):275-86. doi: 10.1016/j.ccr.2005.02.009.
Results publicationGarcia-Manero G, Fenaux P. Comprehensive Analysis of Safety: Rigosertib in 557 Patients with Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML). Blood Dec 2016, 128 (22) 2011; ASH 2016.
Website of Albert Einstein Cancer Center.Link provided by the sponsor.

Related trials for Advanced Solid Tumors

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
RecruitingPhase 1/2
A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Locally Advanced Solid Tumor, Metastatic Solid Tumor
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Sridhar Mani, MD principal investigator

Albert Einstein College of Medicine

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ON 01910.Na and irinotecan and ON 01910.Na and oxaliplatin in people with Advanced Solid Tumors, run by Traws Pharma, Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

maximum tolerated dose (time frame: 1 - 3 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00861328, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2017.