A Phase II Study of Oral Rigosertib in Patients With Relapsed or Metastatic, Platinum-resistant, Human Papillomavirus Positive or Negative Squamous Cell Carcinoma
This will be a multicenter, Phase II study to evaluate the safety and efficacy of oral
rigosertib in patients with relapsed or metastatic squamous cell carinoma (SCC) who
previously received platinum-based chemotherapy and/or chemo-radiation therapy.
Only patients with head and neck squamous cell carinoma (HNSCC), non-small cell lung SCC,
skin SCC, cervical SCC, penile SCC, anal SCC or esophageal SCC will be enrolled in the
Patients will be administered rigosertib capsules at a dose of 560 mg BID on days 1 to 14 of
a 21-day cycle. Patients will be enrolled in 2 cohorts based on HPV test results:
- Cohort 1 will include up to 40 patients with human papillomavirus (HPV)-positive SCC,
of which approximately 30 patients will have HNSCC, and approximately 10 patients with
SCC of another origin (eg, cervix, anal, penile);
- Cohort 2 will include up to 40 patients with HPV-negative SCC, of which approximately
30 patients will have HNSCC, and approximately 10 patients with SCC of another origin
(eg, lung, skin, esophageal).
Patients will be evaluated for progression after completing 3 cycles of therapy and every 3
cycles thereafter. Patients with stable disease (SD) or better, based on revised Response
Criteria in Solid Tumors (mRECIST) 1.1, will receive repeated cycles of treatment on a
21-day cycle schedule until disease progression, development of unacceptable toxicity, or
withdrawal of consent. Patients with progressive disease (PD) but who, in the opinion of the
Investigator, appear to be deriving clinical benefit, may continue on study with a planned
disease reassessment after one further cycle of therapy. Should the patient have SD or PR at
this reassessment, s/he may continue on study, with subsequent reassessments every 3 cycles.
Following discontinuation of rigosertib treatment, patients' mortality status will be
assessed every 3 months.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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.
François E. Wilhelm, MD, PhD
Onconova Therapeutics, Inc.
United States: Food and Drug Administration
|Mary Crowley Cancer Research Center||Dallas, Texas 75246|
|Virginia Cancer Specialists, PC||Fairfax, Virginia 22031|
|University of Colorado School of Medicine||Aurora, Colorado|
|Denver VA Medical Center-ECHCS||Denver, Colorado 80220|
|University of Pennslvania Abramson Cancer Center||Philadelphia, Pennsylvania 19104|