Oral Rigosertib for Squamous Cell Carcinoma

NCT01807546 | Completed Phase 2

• 2 other identifiers: Onconova 09-09COMIRB 13-0116
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 13

Brief 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.

Conditions

Head and Neck Squamous Cell Carcinoma; Anal Squamous Cell Carcinoma; Lung Squamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Penile Squamous Cell Carcinoma

Keywords

Head and neck cancer; Platinum-resistant; Squamous cell carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  Outcome is defined as the number of patients with Complete Response (CR) or Partial Response (PR) per revised Response Evaluation Criteria In Solid Tumors (RECIST 1.1). Complete response (CR) is defined as disappearance of all target lesions. Partial Response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  Baseline to 9 weeks after start of rigosertib treatment and every 9 weeks thereafter, up to 2 years.

Secondary Outcomes (5)

• Overall survival (OS)

  Date of signing ICF to date of death, or date last known to be alive up to 2 years after discontinuation of rigosertib treatment.

• Progression free survival (PFS),

  9 weeks, 18 weeks, and 27 weeks and every 9 weeks thereafter, up to 2 years after patient enrolled in the study.

• Concentration of rigosertib in plasma

  Cycle 1 Day 1, Cycle 1 Day 14 and Cycle 2 Day 14 at 0, 0.5, 1, 1.5, 2, and 6 hours after the first dose of the day.

• Levels of Biomarkers

  Baseline ( study before drug administration) and Cycle 1, Day 14.

• Number of Adverse Events

  From signing of Informed Consent Form until 30 days after last dose of study drug.

Study Arms (1)

rigosertib

EXPERIMENTAL

Oral rigosertib capsules at a dose of 560 mg twice a day for 14 consecutive days of a 21-day cycle (2 weeks on, 1 week off regimen).

Drug: rigosertib

Interventions

rigosertib DRUG

Oral rigosertib capsules at a dose of 560 mg twice a day for 14 consecutive days of a 21-day cycle (2 weeks on, 1 week off regimen).

Also known as: ON 01910.Na

rigosertib

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed SCC; only patients with HNSCC, non-small cell lung SCC, skin SCC, cervical SCC, penile SCC, anal SCC, or esophageal SCC;
• 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 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;
• 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;
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2;
• Life expectancy of at least 3 months;
• Measurable disease according to RECIST version 1.1;
• Ability to swallow entire capsules;
• Adequate hematologic function;
• Adequate hepatic function;
• Adequate renal function;
• Adequate contraceptive regimens for female and male patients;
• Female patients with reproductive potential must have a negative urine or serum pregnancy test;
• 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;
• Willingness to adhere to the prohibitions and restrictions specified in this protocol;

You may not qualify if:

• Chemotherapy or any potentially myelosuppressive treatment within 3 weeks prior to enrollment (6 weeks are required for nitrosoureas or mitomycin C);
• Radiotherapy to \>25% of the hematopoietic active bone marrow within 4 weeks prior to enrollment;
• Systemic administration of corticosteroids within the past 4 weeks prior to enrollment;
• Prior therapy with a phosphatidylinositol 3-kinase (PI3K), Akt or mammalian target of rapamycin (mTOR) inhibitor;
• Any other investigational agent or chemotherapy, radiotherapy, or immunotherapy within 4 weeks of enrollment;
• Major surgery within 3 weeks of enrollment or major surgery without full recovery;
• 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;
• 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;
• Ascites requiring active medical management, including paracentesis;
• 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.);
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, bleeding, symptomatic congestive heart failure, unstable angina pectoris, and cardiac arrhythmia;
• Uncontrolled hypertension, defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥110 mmHg;
• New onset of seizures within 3 months prior to enrollment, or poorly controlled seizures;
• Psychiatric illness/social situations that would limit the patient's ability to tolerate and/or comply with study requirements;
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to rigosertib;

Sponsors & Collaborators

• Traws Pharma, Inc.: lead

Study Sites (13)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Stanford Cancer Institute

Stanford, California, 94305, United States

Location

University of Colorado School of Medicine

Aurora, Colorado, 80045, United States

Location

Denver VA Medical Center-ECHCS

Denver, Colorado, 80220, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Veterans Administration New Jersey Health Care System

East Orange, New Jersey, 07018, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Ohio State University, James Cancer Hospital

Columbus, Ohio, 43210, United States

Location

University of Pennslvania Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Mary Crowley Cancer Research Center

Dallas, Texas, 75201, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Blue Ridge Cancer Care

Salem, Virginia, 24153, United States

Location

Related Publications (2)

• Anderson RT, Keysar SB, Bowles DW, Glogowska MJ, Astling DP, Morton JJ, Le P, Umpierrez A, Eagles-Soukup J, Gan GN, Vogler BW, Sehrt D, Takimoto SM, Aisner DL, Wilhelm F, Frederick BA, Varella-Garcia M, Tan AC, Jimeno A. The dual pathway inhibitor rigosertib is effective in direct patient tumor xenografts of head and neck squamous cell carcinomas. Mol Cancer Ther. 2013 Oct;12(10):1994-2005. doi: 10.1158/1535-7163.MCT-13-0206. Epub 2013 Jul 19.

  PMID: 23873848 BACKGROUND

• 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.

  RESULT

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Anus Neoplasms; Esophageal Squamous Cell Carcinoma; Head and Neck Neoplasms; Carcinoma, Squamous Cell

Interventions

ON 01910

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Esophageal Diseases

Study Officials

• Michael Kurman, MD

  Traws Pharma, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2013
• First Posted: March 8, 2013
• Study Start: March 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: April 1, 2016
• Last Updated: June 26, 2017

Record last verified: 2017-06

Locations

US (13)