Solid Tumors Clinical Trial
Official title:
Phase I Dose Escalation Study of Gemcitabine and ON 01910.Na in Patients With Advanced or Metastatic Solid Tumors
Verified date | June 2017 |
Source | Onconova Therapeutics, Inc. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Treatment of cancer is often more effective when two or more drugs are used together. For example, when gemcitabine, an approved drug, and ON 01910.Na, a new investigational anti-cancer drug, are used together to treat cancer cells in laboratory animals, there is more inhibition of the growth of the cancer cells compared to either drug used by itself. These results offer promise that gemcitabine and ON 01910.Na could be used to treat cancer in patients. However, before studies that seek to find out if gemcitabine and ON 01910.Na is an effective combination in patients can be done, doctors must first know what is largest, safe dose of ON 01910.Na that can be used in combination with gemcitabine. This study is designed to answer that question.
Status | Completed |
Enrollment | 39 |
Est. completion date | September 2011 |
Est. primary completion date | September 2011 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - Patients with histologically confirmed solid malignancy for which standard curative or palliative measures do not exist or are no longer effective; or patients with a clinical rationale for a gemcitabine-based therapy. - The last radiotherapy/chemotherapy dose must have been given =4 weeks prior to study drug initiation; with any acute or chronic adverse events of prior radiotherapy or chemotherapy having resolved to <Grade 2 as determined by CTCAE v3.0. - Patients must have a life expectancy of at least 12 weeks and an ECOG performance status of <1. - Patients must be >18 years of age. - Patients must have evaluable disease, either with informative tumor markers, or with measurable disease on imaging, by RECIST (Response Evaluation Criteria in Solid Tumors) criteria (Appendix II). - Patients must have adequate liver and renal function as defined by serum creatinine no greater than 2.0 times the institution's upper normal limits (or a 24 hour creatinine clearance of >50 ml/min) and total bilirubin level no greater than 2.0 times the institution's upper normal limits and transaminase levels no higher than 3.0 times the institution's upper normal limits. (Note that patients with primary liver cancer or hepatic metastases may have a total bilirubin value of up to 1.5 mg/dl and transaminase levels of up to 5.0 times the limit of normal). - Patients must have adequate bone marrow function as defined by a granulocyte count of >1,500/mm3, platelet count of >100,000/mm3, and hemoglobin >9 g/dl. - Patients at the expanded phase at the MTD must be willing and able to undergo blood sampling for pharmacokinetic studies in Course 1. - For patients in the expanded phase at the MTD, tumor amenable to a single tumor biopsy, and willingness to undergo a baseline tumor biopsy. - Patients must sign an informed consent form indicating that they are aware of the investigational nature of this study and in keeping with the policies of the institution. Exclusion Criteria: Patients will be excluded if: - They have evidence of active heart disease including myocardial infarction within the previous 3 months; symptomatic coronary insufficiency or heart block; uncontrolled congestive heart failure; moderate or severe pulmonary dysfunction. - They have an active infectious process. - They have active central nervous system metastases. - They have received prior radiotherapy administered to more than 30% of marrow-bearing bone mass. - They have ascites requiring active medical management including paracentesis more than twice a month or hyponatremia (defined as serum sodium value of <134 Meq/L). - Women who are pregnant or lactating. - Male patients with female sexual partners who are unwilling to follow the strict contraception requirements described in this protocol (see Section 5.4). - Patients who have had major surgery without full recovery or major surgery within 3 weeks of ON 01910.Na treatment start. |
Country | Name | City | State |
---|---|---|---|
United States | Roswell Park Cancer Institute | Buffalo | New York |
United States | University of Colorado Cancer Center | Denver | Colorado |
Lead Sponsor | Collaborator |
---|---|
Onconova Therapeutics, Inc. |
United States,
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.
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. — View Citation
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. — View Citation
Jimeno A, Rubio-Viqueira B, Rajeshkumar NV, Chan A, Solomon A, Hidalgo M. A fine-needle aspirate-based vulnerability assay identifies polo-like kinase 1 as a mediator of gemcitabine resistance in pancreatic cancer. Mol Cancer Ther. 2010 Feb;9(2):311-8. doi: 10.1158/1535-7163.MCT-09-0693. Epub 2010 Jan 26. — View Citation
Ma WW, Messersmith WA, Dy GK, Weekes CD, Whitworth A, Ren C, Maniar M, Wilhelm F, Eckhardt SG, Adjei AA, Jimeno A. Phase I study of Rigosertib, an inhibitor of the phosphatidylinositol 3-kinase and Polo-like kinase 1 pathways, combined with gemcitabine in — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Adverse events | Incidence of adverse events, including laboratory parameters, as assessed by NCI CTCAE v3.0. | Start of treatment to 30 days after end of treatment. | |
Primary | Maximum tolerated dose (MTD) of ON 01910.Na | MTD will be defined as the highest dose level of ON 01910.Na at which none of the first three patients or no more than one of six patients experienced dose limiting toxicity (DLT) in course 1. | Escalation phase of protocol. | |
Secondary | Pharmacokinetics | Plasma concentration values of ON 01910.Na will be analyzed to determine if gemcitabine has an effect on pharmacokinetic parameters of ON 01910.Na. | Confirmation phase of protocol. | |
Secondary | Tumor measurements | Tumors will be measured to determine response according to RECIST criteria. | Screening to 30 days after end of treatment. | |
Secondary | Pharmacodynamics, ex vivo | Use tumor tissue obtained by biopsy to assess the pharmacodynamic activity of the ON 01910.Na and gemcitabine combination. | Confirmation phase of protocol. |
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT00750841 -
Study of the Effect of Rifampicin on the Pharmacokinetics (PK) of Multiple Doses of Cediranib in Patients With Solid Tumours
|
Phase 1 | |
Withdrawn |
NCT05419817 -
Pembrolizumab With Sitravatinib in Recurrent Endometrial Cancer and Other Solid Tumors With Deficient Mismatch Repair System
|
Phase 2 | |
Completed |
NCT02828930 -
A Study to Determine the Excretion Balance, Pharmacokinetics, Metabolism and Absolute Oral Bioavailability of a Single Oral Dose of [14C]-Labeled Idasanutlin and an Intravenous Tracer Dose of [13C]-Labeled Idasanutlin in a Single Cohort of Participants With Solid Tumors (Malignancies)
|
Phase 1 | |
Completed |
NCT01197170 -
Hormone Receptor Positive Disease Across Solid Tumor Types: A Phase I Study of Single-Agent Hormone Blockade and Combination Approaches With Targeted Agents to Provide Synergy and Overcome Resistance
|
Phase 1 | |
Terminated |
NCT03225105 -
M3541 in Combination With Radiotherapy in Solid Tumors
|
Phase 1 | |
Completed |
NCT03258515 -
A Study to Investigate the Effect of Single Dose of AZD6094 (600 mg) on Cardiac Repolarization in Healthy Volunteers
|
Phase 1 | |
Completed |
NCT01497925 -
Ph 1 Trial of ADI-PEG 20 Plus Docetaxel in Solid Tumors With Emphasis on Prostate Cancer and Non-Small Cell Lung Cancer
|
Phase 1 | |
Completed |
NCT01878890 -
Phase I Dose Escalation Trial of Efavirenz in Solid Tumours or Non-Hodgkin Lymphoma in Therapeutic Failure.
|
Phase 1 | |
Active, not recruiting |
NCT05059522 -
Continued Access Study for Participants Deriving Benefit in Pfizer-Sponsored Avelumab Parent Studies That Are Closing
|
Phase 3 | |
Active, not recruiting |
NCT03634982 -
Dose Escalation of RMC-4630 Monotherapy in Relapsed/Refractory Solid Tumors
|
Phase 1 | |
Recruiting |
NCT04685226 -
A Phase I/II Clinical Trial of ICP-723 in the Treatment of Advanced Solid Tumors
|
Phase 1/Phase 2 | |
Recruiting |
NCT03175224 -
APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors
|
Phase 2 | |
Recruiting |
NCT06036121 -
A Study of ADRX-0706 in Select Advanced Solid Tumors
|
Phase 1 | |
Active, not recruiting |
NCT03258151 -
Association of Genetic Polymorphisms With Docetaxel-based Chemotherapy Toxicities in Chinese Solid Tumor Patients
|
||
Completed |
NCT01528046 -
Metformin in Children With Relapsed or Refractory Solid Tumors
|
Phase 1 | |
Recruiting |
NCT05325866 -
A Study Evaluating Bemarituzumab in Solid Tumors With Fibroblast Growth Factor Receptor 2b (FGFR2b) Overexpression
|
Phase 1/Phase 2 | |
Recruiting |
NCT04557449 -
Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors
|
Phase 1/Phase 2 | |
Completed |
NCT02759640 -
A Phase I Trial of HS-10241 in Solid Tumors
|
Phase 1 | |
Terminated |
NCT02890368 -
Trial of Intratumoral Injections of TTI-621 in Subjects With Relapsed and Refractory Solid Tumors and Mycosis Fungoides
|
Phase 1 | |
Completed |
NCT02279433 -
A First-in-human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of DS-6051b
|
Phase 1 |