Gemcitabine Plus Ascorbate for Sarcoma in Adults

NCT03468075 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 201802800 (Phase II)
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This study will enroll patients who have a diagnosis of locally advanced, unresectable or metastatic soft tissue or bone sarcoma (except gastrointestinal stromal tumors and Kaposi's sarcoma) from any site.

Conditions

Sarcoma; Soft Tissue Sarcoma; Unresectable Soft Tissue Sarcoma; Metastatic Bone Tumor; Bone Sarcoma

Keywords

Sarcoma; Soft tissue; Ascorbate

Outcome Measures

Primary Outcomes (1)

• Tumor Response

  From first day of treatment to documented disease progression as described by RECIST 1.1 criteria. Results are provided in nominal categories (CR, PR, SD, PD) as per RECIST.

  Every 2 months for first 6 months, then every 3 months up to 2 years post treatment

Secondary Outcomes (3)

• Progression Free Survival

  Every 2 months for first 6 months, then every 3 months up to 2 years post treatment

• Overall Survival

  Every 2 months for first 6 months, then every 3 months up to 2 years post treatment

• Incidence of Adverse Events (AE) Per CTCAE 4.03

  Up to 30 days after completion of study treatment

Study Arms (1)

Gemcitabine + High-Dose Ascorbate

EXPERIMENTAL

Subjects will receive ascorbate, 75g, on Days 1, 2, 8, 9, 15 and 16 of a 28-day cycle. Gemcitabine will be administered on Days 1, 8 and 15, after the infusion of ascorbate. Concomitant treatment will continue for 6 cycles. Patients whose disease has not progressed while receiving gemcitabine and ascorbate and who are tolerating therapy may continue either single agent gemcitabine or concomitant treatment beyond 6 cycles at the discretion of the investigator.

Drug: Ascorbate; Drug: Gemcitabine

Interventions

Ascorbate DRUG

Following 15g test dose, 75g administered on Days 1, 2, 8, 9, 15 and 16 of a 28-day cycle

Also known as: Ascorbic Acid, Vitamin C, Pharmacological ascorbate

Gemcitabine + High-Dose Ascorbate

Gemcitabine DRUG

Administered on Days 1, 8 and 15, after the infusion of ascorbate

Also known as: Gemzar

Gemcitabine + High-Dose Ascorbate

Eligibility Criteria

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

You may qualify if:

• Male or female patients aged ≥ 18 years old
• ECOG Performance Status of ≤ 2
• Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
• Patients must meet the following laboratory criteria:
• Hematology:
• Neutrophil count of \>1500/mm3
• Platelet count of \> 100,000/mm3L
• Hemoglobin ≥ 9 g/dL (transfusion to meet eligibility allowed)
• Biochemistry:
• AST/SGOT and ALT/SGPT ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0 x ULN if the transaminase elevation is due to disease involvement
• Alkaline phosphatase \< 5 x ULN
• Serum bilirubin ≤ 1.5 x ULN
• Serum creatinine ≤ 1.5 x ULN or 24-hour creatinine clearance ≥ 50 ml/min
• Total serum calcium \>/= LLN or if calcium is below LLN then corrected calcium for serum albumin should be \>/= LLN
• Serum potassium ≥ LLN

You may not qualify if:

• G6PD (glucose-6-phosphate dehydrogenase) deficiency
• New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E)
• History of myocardial infarction or unstable angina within 6 months prior to Day 1
• History of stroke or transient ischemic attack within 6 months prior to Day 1
• Known CNS disease, except for treated brain metastasis: Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded
• Actively receiving insulin or requiring fingerstick glucose monitoring at time of ascorbate infusion (unless an exception is granted by the IND sponsor, medical monitor, and the PI).
• Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
• Pregnancy (positive pregnancy test) or lactation. Use of effective means of contraception (men and women) in subjects of child-bearing potential
• Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide. High dose ascorbic acid may affect urine acidification and, as a result, may affect clearance rates of these drugs.
• Other concurrent severe and/or uncontrolled medical conditions
• Patients who have received chemotherapy or any investigational drug \< 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study.
• Concomitant use of any anti-cancer therapy or radiation therapy. Palliative radiation therapy to non-target lesions is permitted.
• Male patients whose sexual partners are WOCBP not using a double method of contraception during the study and 3 months after the end of treatment. One of these methods must be a condom.

Sponsors & Collaborators

• Mohammed Milhem, MBBS: lead
• University of Iowa: collaborator
• St. Baldrick's Foundation: collaborator

Study Sites (1)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Sarcoma; Bone Neoplasms

Interventions

Ascorbic Acid; Gemcitabine

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Bone Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

Study terminated early. Ten patients were enrolled in the first stage, and per protocol the study was terminated following interim analysis when 1 or fewer participants had a tumor response.

Results Point of Contact

• Title: Clinical Assistant Professor
• Organization: University of Iowa, Holden Comprehensive Cancer Center

varun-monga@uiowa.edu

319-384-9497

Study Officials

• Varun Monga, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Clinical Professor

Study Record Dates

• First Submitted: March 9, 2018
• First Posted: March 16, 2018
• Study Start: July 11, 2018
• Primary Completion: April 16, 2019
• Study Completion: October 19, 2020
• Last Updated: December 10, 2020
• Results First Posted: December 10, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)