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A Phase II Study of Oral Rigosertib in Patients With Relapsed or Metastatic, Platinum-resistant, Human Papillomavirus Positive or Negative Squamous Cell Carcinoma

Phase 2
18 Years
Open (Enrolling)
Head and Neck Squamous Cell Carcinoma, Anal Squamous Cell Carcinoma, Lung Squamous Cell Carcinoma, Cervical Squamous Cell Carcinoma, Esophageal Squamous Cell Carcinoma

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Trial Information

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.

Inclusion Criteria:

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

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

3. Incurable, non-resectable local relapsed and/or distant metastatic disease after no
more than 3 prior treatment regimens for advanced cancer, one of which must be
platinum-based chemotherapy or chemo-radiation therapy;

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

5. Life expectancy of at least 3 months;

6. Measurable disease according to RECIST version 1.1;

7. Ability to swallow entire capsules;

8. Adequate hematologic function;

9. Adequate hepatic function;

10. Adequate renal function

11. Adequate contraceptive regimens for female and male patients.

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

13. 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;

14. Willingness to adhere to the prohibitions and restrictions specified in this

15. 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. Prior doxorubicin therapy at a total cumulative dose exceeding 450 mg/m2;

3. Definitive radiotherapy (ie, over 10 fractions and maximal area of hematopoietic
active bone marrow treated ˃25%) within 4 weeks prior to enrollment;

4. Palliative radiotherapy (ie, 10 fractions or less) within 2 weeks prior to

5. Systemic administration of corticosteroids within the past 4 weeks prior to

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

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

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

9. 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

10. 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;

11. Ascites requiring active medical management, including paracentesis;

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

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

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

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

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

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

18. Female patients who are pregnant or lactating.

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall response rate

Outcome Description:

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.

Outcome Time Frame:

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

Safety Issue:


Principal Investigator

François E. Wilhelm, MD, PhD

Investigator Role:

Study Director

Investigator Affiliation:

Onconova Therapeutics, Inc.


United States: Food and Drug Administration

Study ID:

Onconova 09-09



Start Date:

March 2013

Completion Date:

September 2015

Related Keywords:

  • Head and Neck Squamous Cell Carcinoma
  • Anal Squamous Cell Carcinoma
  • Lung Squamous Cell Carcinoma
  • Cervical Squamous Cell Carcinoma
  • Esophageal Squamous Cell Carcinoma
  • Head and neck cancer
  • Platinum-resistant
  • Squamous cell carcinoma
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Esophageal Diseases
  • Anus Neoplasms
  • Head and Neck Neoplasms



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