Platinum-based Chemoradiotherapy and Rigosertib in Head and Neck Cancer

NCT02107235 | Completed Phase 1

• 1 other identifier: Onconova 09-12
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 4

Brief Summary

The working hypothesis is that oral rigosertib treatment when added to platinum-based Chemoradiotherapy (CRT) will improve progression-free survival for first-line patients with intermediate- or high-risk human papillomavirus negative positive (HPV (+)) Head and Neck Squamous Cell Carcinoma. This study will determine the highest safe dose of oral rigosertib that can be used with cisplatin and CRT. This study will also record any side effects that may occur and measure tumor sizes and how long patients live.

Conditions

Head and Neck Neoplasms; Carcinoma, Squamous Cell

Keywords

Chemoradiotherapy; cisplatin

Outcome Measures

Primary Outcomes (1)

• Number of patients who experience dose limiting toxicities

  The primary objective of the study is to determine the maximum tolerated dose (MTD) of oral rigosertib when administered with platinum-based chemoradiotherapy to patients with intermediate- and high-risk Head and Neck Squamous Cell Carcinoma. The MTD is defined as the dose level immediately below that at which 2 or more patients experience a dose limiting toxicity (DLT).

  Up to 12 weeks

Secondary Outcomes (2)

• Number of patients who experience adverse events

  Up to 14 weeks

• Number of patients who achieve a complete response or a partial response

  Up to 3 years

Study Arms (1)

Rigosertib + Cisplatin + Radiation

EXPERIMENTAL

Oral rigosertib will be started 7 days before initiation of concurrent treatment with cisplatin and radiation therapy and will be administered on a continuous basis for a fixed duration of 8 weeks. Three oral rigosertib escalating doses will be sequentially evaluated: 70 mg 3 times a day (TID), 140 mg TID and 280 mg TID. Cisplatin will be administered intravenously at a dose of 40 mg/m\^2 on Days 1, 8, 15, 22, 29, 36, and 43 of the 7-week concurrent treatment course. The prescribed radiotherapy dose will be 70 Gray (Gy) in 2 Gy once-daily fraction size (total of 35 fractions) over the 7-week concurrent treatment course. The initial target volume encompassing the gross and subclinical disease sites will receive 2.0 Gy per fraction, 5 fractions per week.

Drug: oral rigosertib; Drug: cisplatin; Radiation: Radiotherapy

Interventions

oral rigosertib DRUG

Also known as: ON 01910.Na, rigosertib sodium

Rigosertib + Cisplatin + Radiation

cisplatin DRUG

Rigosertib + Cisplatin + Radiation

Radiotherapy RADIATION

Rigosertib + Cisplatin + Radiation

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed diagnosis of Squamous Cell Carcinoma of the oropharynx (tonsil, base of tongue, soft palate, or oropharyngeal wall), hypopharynx, or larynx.
• Patient is an appropriate candidate for definitive chemoradiotherapy.
• Intermediate-risk Head and Neck Squamous Cell Carcinoma (HNSCC), defined as follows:
• Clinical stage T2-4, N2a-N3 or T3-4, N0-N3
• P16 (+) by immunohistochemistry (IHC) or HPV (+) by in situ hybridization (ISH)
• Smoking status of ≥ 10 pack-years, or \< 10 pack-years and T4 or N2c-N3.
• If not intermediate-risk HNSCC, is high-risk HNSCC, defined as follows:
• Clinical stage T2-4, N2a-N3 or T3-4, N0-N3.
• P16 (-) by IHC or HPV (-) by ISH.
• No evidence of distant metastases.
• Clinically or radiographically evident measurable disease (as defined by RECIST v 1.1) at the primary site or nodal stations.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate hematologic function as defined by absolute neutrophil count (ANC) ≥ 1800/μL; platelet (PLT) ≥ 100,000/μL; Hgb ≥ 8.0 g/dL.
• Adequate renal function, as defined by serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min.
• Adequate liver function as defined by total bilirubin ≤ 1.5 x ULN; aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 2.5 x ULN; and prothrombin time ≤ 1.5 x ULN, unless receiving therapeutic anticoagulation.

You may not qualify if:

• Gross total excision of the primary and nodal disease.
• Prior treatment with IV or oral rigosertib.
• Prior chemotherapy for the study HNSCC cancer.
• Prior radiotherapy to the region of the study HNSCC cancer or adjacent anatomical sites, or to \> 25% of marrow-bearing area.
• Synchronous malignancies.
• Prior invasive malignancy unless the patient is disease-free for a minimum of 3 years; however, patients with prior non-melanoma skin cancer, cervical intraepithelial neoplasia (CIN), or prostate cancer with undetectable prostate-specific antigen (PSA) may be enrolled.
• Severe, active comorbidity.
• Known infection with human immunodeficiency virus (HIV).
• Any uncontrolled condition that, in the opinion of the Investigator, could affect the subject's participation in the study.
• Major surgery within 3 weeks of enrollment or major surgery without full recovery.
• Ascites requiring active medical management, including paracentesis.
• Hyponatremia (defined as serum sodium \< 130 milliequivalent mEq/L) or conditions that may predispose patients to hyponatremia.
• Uncontrolled hypertension, defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 110 mmHg, despite treatment with 2 antihypertensive agents.
• New onset of seizures within 3 months prior to enrollment, or poorly controlled seizures.
• Female patients who are pregnant or lactating.

Sponsors & Collaborators

• Traws Pharma, Inc.: lead

Study Sites (4)

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Christiana Care Health Services

Newark, Delaware, 19713, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• 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

Head and Neck Neoplasms; Carcinoma, Squamous Cell

Interventions

ON 01910; Cisplatin; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Therapeutics

Study Officials

• Antonio Jimeno, MD, PhD

  University of Colorado, Denver

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2014
• First Posted: April 8, 2014
• Study Start: January 1, 2014
• Primary Completion: October 1, 2014
• Study Completion: January 1, 2015
• Last Updated: June 23, 2017

Record last verified: 2017-06

Locations

US (4)