Oral Rigosertib for Squamous Cell Carcinoma

• Status: Completed
• Trial end date: 2016-04-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of this study is to determine if tumors in patients with papillomavirus (HPV) positive or negative squamous cell carcinoma (SCC) that no longer responds to standard therapy will decrease in size following treatment with the investigational drug, rigosertib sodium (ON 01910.Na). A secondary objective is to determine if treatment with rigosertib causes any side effects.

Rigosertib is an investigational drug, which means that it has not been approved by the U.S. Food and Drug Administration (FDA) to treat any diseases. We are studying rigosertib as a new anticancer drug. Tests that we have done in the laboratory suggest that rigosertib works by blocking cell division in cancer cells and causing them to die.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Onconova Therapeutics, Inc.
• Treatments: ON 01910

Criteria

Inclusion Criteria:

1. Histologically confirmed SCC; only patients with HNSCC, non-small cell lung SCC, skin SCC, cervical SCC, penile SCC, anal SCC, or esophageal SCC;

2. For patients with HNSCC only, HPV status must be assessed by in situ hybridization (ISH) and/or p16 immunohistochemistry (IHC) according to local standards;

3. For patients with HNSCC only, HPV status must be assessed by in situ hybridization (ISH) and/or p16 immunohistochemistry (IHC) according to local standards. For all other patients with SCC originating in tissues other than the head and neck, attempts should be made to obtain HPV status;

4. Incurable, non-resectable, locally-advanced/relapsed and/or distant metastatic disease after no more than 3 prior treatment regimens, one of which must be platinum-based chemotherapy;

5. Eastern Cooperative Oncology Group (ECOG) performance status ≤2;

6. Life expectancy of at least 3 months;

7. Measurable disease according to RECIST version 1.1;

8. Ability to swallow entire capsules;

9. Adequate hematologic function;

10. Adequate hepatic function;

11. Adequate renal function;

12. Adequate contraceptive regimens for female and male patients;

13. Female patients with reproductive potential must have a negative urine or serum pregnancy test;

14. Ability to understand the nature of the study and any hazards of study participation, to communicate satisfactorily with the Investigator, and to follow the requirements of the entire protocol;

15. Willingness to adhere to the prohibitions and restrictions specified in this protocol;

16. The patient must sign an informed consent form (ICF).

Exclusion Criteria:

1. Chemotherapy or any potentially myelosuppressive treatment within 3 weeks prior to enrollment (6 weeks are required for nitrosoureas or mitomycin C);

2. Radiotherapy to >25% of the hematopoietic active bone marrow within 4 weeks prior to enrollment;

3. Systemic administration of corticosteroids within the past 4 weeks prior to enrollment;

4. Prior therapy with a phosphatidylinositol 3-kinase (PI3K), Akt or mammalian target of rapamycin (mTOR) inhibitor;

5. Any other investigational agent or chemotherapy, radiotherapy, or immunotherapy within 4 weeks of enrollment;

6. Major surgery within 3 weeks of enrollment or major surgery without full recovery;

7. Residual clinical signs and symptoms which have not recovered to Common Terminology Criteria for Adverse Events (CTCAE) version 4 Grade 1 severity level or below before enrollment, except for alopecia, stable residual neuropathy, and residual hand/foot syndrome;

8. Known brain metastases, except for those that have been removed or irradiated and have no current clinical impact at the time of enrollment; a computed tomography (CT) scan or magnetic resonance imaging (MRI) of the brain should be obtained in patients with symptoms suggestive of brain metastases;

9. Ascites requiring active medical management, including paracentesis;

10. Serum sodium less than 130 mEq/L or conditions that may predispose patients to hyponatremia (eg, previous syndrome of inappropriate antidiuretic hormone hypersecretion [syndrome of inappropriate antidiuretic hormone secretion (SIADH)], chronic diuretic use, etc.);

11. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, bleeding, symptomatic congestive heart failure, unstable angina pectoris, and cardiac arrhythmia;

12. Uncontrolled hypertension, defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥110 mmHg;

13. New onset of seizures within 3 months prior to enrollment, or poorly controlled seizures;

14. Psychiatric illness/social situations that would limit the patient's ability to tolerate and/or comply with study requirements;

15. History of allergic reactions attributed to compounds of similar chemical or biologic composition to rigosertib;

16. Female patients who are pregnant or lactating.