High Dose Ascorbate With Preoperative Radiation in Patients With Locally Advanced Soft Tissue Sarcomas

NCT03508726 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 201901810
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm open-label phase Ib/II clinical study assessing the efficacy of concurrent high dose ascorbate in combination with radiotherapy in patients with locally advanced, resectable, high grade sarcomas.

Conditions

Soft Tissue Sarcoma

Keywords

Sarcoma; Soft tissue

Outcome Measures

Primary Outcomes (2)

• Number of Participants That Experienced Dose Limiting Toxicities (DLTs) Using CTCAE, Version 4.0

  To examine the toxicity related to the therapy by measuring the number attributed adverse event (definite, probable or possible) according to CTCAE version 4.0.

  Start of treatment up to 4 weeks after the last ascorbate infusion

• Number of Participants With Pathologic Tumor Necrosis ≥ 95% Following Concurrent Radiation Therapy and Ascorbate

  To estimate the efficacy of neoadjuvant ascorbate and radiotherapy as assessed by the pathological complete response rates (pCR) in subjects with locally advanced high grade soft tissue sarcomas.

  Start of treatment up to 6 weeks after the last ascorbate infusion

Secondary Outcomes (6)

• Disease Progression as Measured by Time to Disease Progression (TTP)

  Enrollment or start of treatment up to 2 years following end of treatment

• Overall Response Rate as Measured by RECIST 1.1

  Enrollment or start of treatment up to 2 years following end of treatment

• Overall Survival Estimated Using the Kaplan-Meier Method

  Enrollment or start of treatment up to 2 years following end of treatment

• Skin Toxicity

  Within two years following end of treatment

• Labile Iron

  Within two years following end of treatment

Study Arms (2)

Phase I dose escalation cohort

EXPERIMENTAL

Participants will receive radiation therapy over 5 weeks, during which time they will be receiving ascorbate infusions three times a week. Ascorbate infusions will be continued until the end of radiation therapy. Surgery will be performed 4-6 weeks from the end of radiation.

Drug: Ascorbate

Phase II Cohort

EXPERIMENTAL

Participants will receive radiation therapy over 5 weeks, during which time they will be receiving intravenous (IV) ascorbate infusions three times a week. Ascorbate infusions will be continued until the end of radiation therapy. Surgery will be performed 4-6 weeks from the end of radiation.

Drug: Ascorbate

Interventions

Ascorbate DRUG

Phase 1 dose escalation: 75gm IV three times a week Phase II portion: 75gm IV three times a week if no dose limiting toxicities are experienced in the Phase I portion. Otherwise, ascorbate dose will be deescalated to 62.5 gm IV

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

Phase I dose escalation cohort; Phase II Cohort

Eligibility Criteria

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

You may qualify if:

• Subject or subject's legally acceptable representative has provided informed consent.
• Histologically confirmed diagnosis of locally advanced soft tissue sarcoma of extremity, trunk or retroperitoneum that is unresectable with clear wide margins, for which preoperative radiotherapy is considered appropriate
• \- Including metastatic (stage IV) disease for which radiotherapy and surgical resection of the primary tumor are indicated.
• Patients do not have histologic subtypes: GIST, Desmoid, Ewing sarcoma, bone sarcomas and Kaposi sarcoma.
• Age ≥18 years.
• Patients with a history of non-melanomatous skin cancer, in situ carcinoma, or low-risk prostate cancer can be enrolled.
• ECOG performance status \</=1.
• Tolerate one test dose (15g) of ascorbate.
• Patient must have measurable disease:
• Tumor size at least \>/= 5 cm in the longest diameter as measured by CT scan or MRI for which radiation is feasible and indicated.

You may not qualify if:

• Inadequate organ function within 21 days of Day 1 of study as defined by:
• Hemoglobin \< 9.0 g/dL
• Absolute neutrophil count (ANC) \</= 1500 per mm3
• Platelet count \</= 100,000 per mm3
• Total bilirubin \>/= 1.5 × ULN. Subjects with direct bilirubin \< ULN with total bilirubin levels \> 1.5 X ULN will not be excluded.
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2.5 × ULN
• Alkaline phosphatase \> 2.5 × ULN
• PT (or INR) and PTT (or aPTT) \>/= 1.5 × ULN
• Creatinine \> 2.0 × ULN
• G6PD (glucose-6-phosphate dehydrogenase) deficiency.
• Prior history of symptomatic oxalate kidney stones within the last year.
• Prior radiation therapy in excess of 20 Gy to the site of the current diagnosis of sarcoma. No overlap with prior radiation fields in excess of 20 Gy is allowed.
• Prior history of receiving pharmacological ascorbate.
• Patients actively receiving insulin therapy and needing daily fingerstick for glucose monitoring.
• Concurrent, clinically significant, active malignancies within two years of study enrollment.

Sponsors & Collaborators

• Mohammed Milhem: lead
• University of Iowa: collaborator

Study Sites (1)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Sarcoma

Interventions

Ascorbic Acid

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Results Point of Contact

• Title: Varun Monga, MD
• Organization: University of Iowa, Holden Comprehensive Cancer Center

varun-monga@uiowa.edu

319-384-9497

Study Officials

• Mohammed Milhem, MBBS

  University of Iowa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: April 13, 2018
• First Posted: April 26, 2018
• Study Start: June 27, 2019
• Primary Completion: June 3, 2022
• Study Completion: June 2, 2024
• Last Updated: June 27, 2024
• Results First Posted: June 6, 2023

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)