A Broad Multi-histology Phase II Study of the Multi-Kinase Inhibitor R935788 (Fostamatinib Disodium) in Advanced Colorectal, Non-small Cell Lung, Head and Neck Hepatocellular and Renal Cell Carcinomas, and Pheochromocytoma and Thyroid Tumors (Multi-H...

NCT00923481 | Completed Phase 2 Results

• 2 other identifiers: 09013809-C-0138
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• The drug R935788 (fostamatanib disodium) is a kinase inhibitor (i.e., it interferes with cell communication and growth and may prevent tumor growth).
• R935788 has shown promising activity in NCI-60 (a panel of 60 diverse human cancer cell lines) against colon cancer, non-small cell lung cancer, and renal cell carcinoma cell lines, as well as in two renal cell xenograft models.
• This is an open-label, Phase II study of R935788. Phase I studies in patients with immune thrombocytopenic purpura, rheumatoid arthritis, and lymphoma have demonstrated safety with a continuous dosing schedule, and a maximum tolerated dose has been established. Objectives:
• To test an experimental drug called R935788 (fostamatinib disodium) for its ability to stop cancer growth signals, thus slowing the growth of cancer cells in laboratory testing.
• To determine the clinical response of R935788 administered orally twice a day on a continuous schedule in patients with colorectal carcinoma, pheochromocytoma, follicular or papillary thyroid cancer, non-small cell lung cancer, hepatocellular, carcinoma of the head and neck, and renal cell carcinoma.
• To evaluate the effects, safety, and biochemical response of R935788 therapy. Eligibility:
• Patients with colorectal carcinoma, pheochromocytoma, follicular or papillary thyroid cancer, non-small cell lung cancer (excluding squamous cell histology), hepatocellular cancer, carcinoma of the head and neck, and renal cell carcinoma whose disease has progressed after any therapy or who have no acceptable standard treatment options.
• Patients must have recovered from toxicities of prior therapies to at least eligibility levels.
• Patients who have received radiation or chemotherapy within 4 weeks of study enrollment are not eligible.
• Women who are pregnant or breastfeeding are not eligible. Design:
• Researchers will conduct the following tests and procedures during the study:
• Clinic visits with a physical exam, including vital signs and blood pressure, every other week during cycle 1, and once a month starting with cycle 2.
• Blood will be drawn weekly during cycle 1, every other week during cycle 2, and once a month starting with cycle 3; urine tests will be conducted depending on results of blood tests.
• Imaging tests, such as computed tomography (CT) scans (a series of x-rays) or ultrasound (an examination using sound waves), will be done every 8 weeks while the patient is receiving R935788.
• R935788 will be administered orally twice a day for 28 days (one cycle). Imaging studies will be obtained every two cycles. Patients will fill in a diary to show when they took the medication and to note any side effects. The 28-day treatment cycle will be repeated as long as the patient is tolerating R935788 and the cancer is either stable or getting better.
• Researchers will conduct the following additional tests to see how the study is affecting the patient:
• Other research blood samples will be collected before treatment, at cycle 1 week 3, at the beginning of cycle 2, and at 8 weeks.
• Optional tumor biopsies will be requested before starting treatment, at cycle 1 day 28.
• Patients with specific lesions or tumors may be asked for an optional tumor biopsy on day 8.

Conditions

Head and Neck Neoplasms; Pheochromocytoma; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Renal Cell

Keywords

Multi-Kinase Inhibitor; Neoplasms; Advanced Cancer; Kidney Cancer; Liver Cancer; Pheochromocytoma; Non-Small Cell Lung Cancer; Colorectal Cancer; Head and Neck Cancer

Outcome Measures

Primary Outcomes (1)

• Response Rate

  Response is assessed by the RECIST (response criteria in solid tumors)criteria. A complete response (CR) is disappearance of all target lesions , partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) is at least a 20% increase in the sum of the LD of target lesions, and stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

  24 months

Secondary Outcomes (1)

• Number of Participants With Adverse Events

  23 months

Study Arms (1)

Multi-kinase inhibitor Fostamatinib Disodium (R935788)

EXPERIMENTAL

200 mg BID was the administered dose for the initial part of the study and then a phase I dose escalation was added with 100 mg as the starting dose.

Drug: Fostamatinib disodium

Interventions

Fostamatinib disodium DRUG

200 mg BID was the administered dose for the initial part of the study and then a phase I dose escalation was added with 100 mg as the starting dose.

Also known as: R9355788

Multi-kinase inhibitor Fostamatinib Disodium (R935788)

Eligibility Criteria

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

You may qualify if:

• Subjects must have histologically documented solid tumors: pheochromocytoma, follicular or papillary thyroid, colorectal, non-small cell lung (excluding squamous cell histology), hepatocellular, head and neck or renal cell origin, whose disease has progressed after any number of prior therapies or who have no acceptable standard treatment options.
• Patients with follicular or papillary thyroid cancer will be eligible if they have metastatic or unresectable, locally advanced disease which is refractory to, or not suitable for, I therapy.
• Diagnosis of malignancy must be confirmed by the Laboratory of Pathology at the Clinical Center, National Institutes of Health (NIH), prior to patient enrollment.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than or equal to 20 mm with conventional techniques or as greater than or equal to 10 mm with spiral computed tomography (CT) scan.
• Life expectancy of greater than 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky greater than or equal to 60%).
• Subjects must have normal organ and marrow function as defined below:
• absolute neutrophil count greater than or equal to 1,500/mcL
• platelets greater than or equal to 100,000/mcL
• total bilirubin within less than or equal to 1.5 institutional upper limit of normal (ULN)
• aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase(SGOT),alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase(SGPT) less than or equal to 2.5 times ULN
• creatinine \< 1.5 times ULN
• creatinine clearance greater than or equal to 60 mL/min/1.73 m\^2 for patients with creatinine levels greater than or equal to 1.5 times institutional upper limit of normal.
• The effects of R935788 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry, for the duration of study participation, and for 1 month after discontinuation of the study. Women of child bearing potential must have a negative pregnancy test in order to be eligible. Should a participant or a participant's partner become pregnant or suspect she is pregnant while participating in this study, the participant should inform the Research Team immediately.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Subjects who have had chemotherapy, biotherapy, or radiotherapy within 4 weeks prior to entering the study, or those who have not recovered from adverse events due to prior therapy.
• A time period of greater than or equal to 2 weeks must have elapsed since a patient was administered any investigational agent as part of a Phase 0 study (also referred to as an early Phase I study or pre-Phase I study where a sub-therapeutic dose of drug is administered) at the principal investigator's (PI's) discretion, and patients should have recovered from any toxicity from prior therapy to eligibility levels.
• Patients must not have other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast.
• Patients who have undergone primary therapy for a prior diagnosis of cancer and are disease free for at least 3 years prior to study entry will be included in the trial.
• Patients may not be receiving any other investigational agents.
• Subjects with known brain metastases are excluded with the exception of those whose brain metastatic disease status has remained stable for at least 3 months since treatment of the brain metastases without steroids (except for maintenance replacement doses) or antiseizure medications.
• Patients cannot be taking enzyme-inducing anti-seizure medications (e.g., phenytoin, carbamazepine, phenobarbital, primidone, oxcarbamazepine); other seizure medications that are not considered enzyme-inducing would be permissible.
• Because there is an unknown but potential risk for adverse events in nursing infants secondary to exposure to this agent, women who are breast feeding are ineligible for this study.
• Patients receiving medications known to induce/inhibit cytochrome P450 3A4 (CYP3A4) will be excluded from this study.
• Patients who must initiate treatment with a CYP3A4 inhibitor while receiving R935788 will be carefully monitored.
• Inhibitors of CYP3A4 include but are not limited to:
• amiodarone,
• clarithromycin,
• erythromycin,
• imatinib,

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Lenders JW, Pacak K, Walther MM, Linehan WM, Mannelli M, Friberg P, Keiser HR, Goldstein DS, Eisenhofer G. Biochemical diagnosis of pheochromocytoma: which test is best? JAMA. 2002 Mar 20;287(11):1427-34. doi: 10.1001/jama.287.11.1427.

  PMID: 11903030 BACKGROUND

• Pacak K, Eisenhofer G, Carrasquillo JA, Chen CC, Li ST, Goldstein DS. 6-[18F]fluorodopamine positron emission tomographic (PET) scanning for diagnostic localization of pheochromocytoma. Hypertension. 2001 Jul;38(1):6-8. doi: 10.1161/01.hyp.38.1.6.

  PMID: 11463751 BACKGROUND

• Gimenez-Roqueplo AP, Favier J, Rustin P, Rieubland C, Crespin M, Nau V, Khau Van Kien P, Corvol P, Plouin PF, Jeunemaitre X; COMETE Network. Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas. Cancer Res. 2003 Sep 1;63(17):5615-21.

  PMID: 14500403 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Head and Neck Neoplasms; Pheochromocytoma; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Renal Cell; Neoplasms; Kidney Neoplasms; Liver Neoplasms

Interventions

fostamatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Paraganglioma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Liver Diseases

Results Point of Contact

• Title: Dr. Shivaani Kummar
• Organization: National Cancer Institute, National Institutes of Health

kummars@mail.nih.gov

301-435-5402

Study Officials

• Shivaani Kummar, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: June 17, 2009
• First Posted: June 18, 2009
• Study Start: April 1, 2009
• Primary Completion: April 1, 2009
• Study Completion: January 1, 2012
• Last Updated: September 30, 2015
• Results First Posted: August 29, 2012

Record last verified: 2012-07

Locations

US (1)