CancerPhase 1/2NCT01050621
Trial of Chemotherapy Plus Intravenous Vitamin C in Patients With Advanced Cancer for Whom Chemotherapy Alone is Only Marginally Effective
A Phase 1/2 study testing vitamin C (ascorbic acid) in people with Cancer, run by Jewish General Hospital at 1 site in Canada.
Trial summary
Concurrent administration of intravenous vitamin C (ascorbic acid, 1.5 g/kg, infused two or three times weekly) together with certain cytotoxic chemotherapy regimens could prove to be an effective treatment for some patients with advanced malignancies for whom existing chemotherapy is usually ineffective. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- vitamin C (ascorbic acid)
- How many people
- 14 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2010to May 2013
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- must be a resident of Quebec, Canada
- documented advanced or metastatic cancer or hematologic malignancy in adults over age 18, with measurable disease
- adequate bone marrow, hepatic, renal and cardiac function so as to permit conventional chemotherapy
- no current calcium oxalate nephrolithiasis with the potential to reduce urinary flow
- life expectancy at least 8 weeks.
Who cannot join
- glucose-6-phosphate dehydrogenase deficiency
- cancers for which existing chemotherapy offers more than a 33% likelihood of a clinically meaningful response
- serum creatinine greater than 175 micromol/L
- serious GI diseases
- infections
- recent major surgery
- dementia
- altered mental status or other condition that would preclude chemotherapy, including poor functional status.
Trial locations and contacts
1 site in 1 country.
Canada1 site
Clinical Research Unit, Jewish General Hospital
Montreal, Quebec, H3T 1E2
About this study
Official title: Phase I - II Clinical Trial of Combination Conventional Cytotoxic Chemotherapy and Intravenous Vitamin C in Patients With Advanced Cancer or Hematologic Malignancy for Whom Cytotoxic Chemotherapy Alone is Only Marginally Effective
Concurrent administration of intravenous vitamin C (ascorbic acid, 1.5 g/kg, infused two or three times weekly) together with certain cytotoxic chemotherapy regimens could prove to be an effective treatment for some patients with advanced malignancies for whom existing chemotherapy is usually ineffective. The primary objectives of this study are to identify a tolerable and safe dose of intravenous vitamin C when administered during cytotoxic chemotherapy while attempting to empirically identify specific vitamin C-chemotherapy regimens for which the clinical response is unusually favorable after a minimum of 2 months of therapy, as determined by CT scan and biomarkers, when appropriate.
Read the detailed description
Cytotoxic chemotherapy is relatively ineffective for a large proportion of common cancers. Combining redox active molecules with certain chemotherapy regimens could increase their anti-cancer activity or protect host tissues from toxicity with no loss of anti-cancer activity. Research in this area has been advocated by cancer organizations, but previous clinical trials of combination chemotherapy and antioxidant therapy been small, poorly designed, and unsystematic. Appropriate study of this treatment concept requires a systematic, meticulous empirical approach similar to the one used in conventional cytotoxic drug discovery. This is a Phase I-II study designed to identify promising chemotherapy-antioxidant protocols and determine their acceptability and limiting toxicity in patients with relentlessly progressive cancers for which conventional chemotherapy is clinically indicated but is known to be minimally or marginally effective.
The tolerable dose of intravenous ascorbic acid (IVAA) for cancer patients with normal renal function not receiving chemotherapy is 1.5 g/kg per 90 to 120 minute infusion (Hoffer et al, Ann Oncol 2008;19:1969-1974). Side effects are minimal to non-existent. In this dose-escalating study the IVAA will be 0.9 g/kg per infusion for the first chemotherapy cycle, increasing to 1.5 g/kg per infusion in subsequent cycles, for the first 3 participants. If well tolerated as expected, the initial dose will be 1.5 g/kg per infusion for subsequent participants. Infusions will take place 2 or 3 times per week, bracketing the days of chemotherapy. Standard tolerance and adverse effect criteria will be used. Therapy will continue for a minimum of 2 months, and continue further in the event of disease stabilization or response, as determined from CT scan and biomarkers, with evaluations continuing every 2 months.
- Conditions
- Cancer
- Being tested
- vitamin C (ascorbic acid)
- Keywords
- ascorbic acid, vitamin C, antioxidants, redox therapy, cytotoxic chemotherapy
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vitamin C (ascorbic acid)Dietary supplement
ascorbic acid 1.5 g/kg body weight infused over 90 to 120 minutes two or three times weekly concurrent with standard cytotoxic chemotherapy individually selected for each patient by the treating oncologist on the basis of best current clinical practice
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of IV ascorbic acid (IVAA) in target dose of 1500 mg/kg supplementing cytotoxic chemotherapeutic drugs. Standard adverse effect criteria will be used.
Measured: At every clinic visit
Observe for qualitative indicators that IV ascorbic acid mitigates chemotherapy adverse effects
Measured: Every treatment cycle
Secondary outcomes (3)
To monitor for disease arrest or response (RECIST criteria) in a population in which arrest or response is unusual or rare
Measured: CT assessment every 2 months
Quality of life assessment using FACT B and POMS R
Measured: every month
Measure the effect of chemotherapy on pharmacokinetics of intravenous ascorbic acid
Measured: Before and 5 days following first chemotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2010 (estimated)
- Study startJan 2010
- Primary completionMay 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jewish General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, John Hoffer, Jewish General Hospital
- Investigators
- Leonard John Hoffer, MD PhD, Principal investigator, Faculty of Medicine, McGill University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01050621
- Sponsor's protocol ID
- VITC-003
- Status last verified
- Jun 2013
- First submitted
- 11 Jan 2010
- Last updated
- 21 Jun 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Hoffer LJ, Robitaille L, Zakarian R, Melnychuk D, Kavan P, Agulnik J, Cohen V, Small D, Miller WH Jr. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial. PLoS One. 2015 Apr 7;10(4):e0120228. doi: 10.1371/journal.pone.0120228. eCollection 2015.
PubMed 25848948
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I - II Clinical Trial of Combination Conventional Cytotoxic Chemotherapy and Intravenous Vitamin C in Patients With Advanced Cancer or Hematologic Malignancy for Whom Cytotoxic Chemotherapy Alone is Only Marginally Effective
- ClinicalTrials.gov ID
- NCT01050621
- Acronym / sponsor ID
- VITC-003
- Conditions
- Cancer
- Keywords
- ascorbic acid, vitamin C, antioxidants, redox therapy, cytotoxic chemotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Jewish General HospitalUniversity, hospital or other
- Study start
- Jan 2010
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 15 Jan 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Concurrent administration of intravenous vitamin C (ascorbic acid, 1.5 g/kg, infused two or three times weekly) together with certain cytotoxic chemotherapy regimens could prove to be an effective treatment for some patients with advanced malignancies for whom existing chemotherapy is usually ineffective. The primary objectives of this study are to identify a tolerable and safe dose of intravenous vitamin C when administered during cytotoxic chemotherapy while attempting to empirically identify specific vitamin C-chemotherapy regimens for which the clinical response is unusually favorable after a minimum of 2 months of therapy, as determined by CT scan and biomarkers, when appropriate.
Detailed description
Cytotoxic chemotherapy is relatively ineffective for a large proportion of common cancers. Combining redox active molecules with certain chemotherapy regimens could increase their anti-cancer activity or protect host tissues from toxicity with no loss of anti-cancer activity. Research in this area has been advocated by cancer organizations, but previous clinical trials of combination chemotherapy and antioxidant therapy been small, poorly designed, and unsystematic. Appropriate study of this treatment concept requires a systematic, meticulous empirical approach similar to the one used in conventional cytotoxic drug discovery. This is a Phase I-II study designed to identify promising chemotherapy-antioxidant protocols and determine their acceptability and limiting toxicity in patients with relentlessly progressive cancers for which conventional chemotherapy is clinically indicated but is known to be minimally or marginally effective.
The tolerable dose of intravenous ascorbic acid (IVAA) for cancer patients with normal renal function not receiving chemotherapy is 1.5 g/kg per 90 to 120 minute infusion (Hoffer et al, Ann Oncol 2008;19:1969-1974). Side effects are minimal to non-existent. In this dose-escalating study the IVAA will be 0.9 g/kg per infusion for the first chemotherapy cycle, increasing to 1.5 g/kg per infusion in subsequent cycles, for the first 3 participants. If well tolerated as expected, the initial dose will be 1.5 g/kg per infusion for subsequent participants. Infusions will take place 2 or 3 times per week, bracketing the days of chemotherapy. Standard tolerance and adverse effect criteria will be used. Therapy will continue for a minimum of 2 months, and continue further in the event of disease stabilization or response, as determined from CT scan and biomarkers, with evaluations continuing every 2 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- must be a resident of Quebec, Canada
- documented advanced or metastatic cancer or hematologic malignancy in adults over age 18, with measurable disease
- adequate bone marrow, hepatic, renal and cardiac function so as to permit conventional chemotherapy
- no current calcium oxalate nephrolithiasis with the potential to reduce urinary flow
- life expectancy at least 8 weeks.
Key exclusion criteria (8 listed)
- glucose-6-phosphate dehydrogenase deficiency
- cancers for which existing chemotherapy offers more than a 33% likelihood of a clinically meaningful response
- serum creatinine greater than 175 micromol/L
- serious GI diseases
- infections
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| vitamin C (ascorbic acid)ascorbic acid 1.5 g/kg body weight infused over 90 to 120 minutes two or three times weekly concurrent with standard cytotoxic chemotherapy individually selected for each patient by the treating oncologist on the basis of best current clinical practice | Dietary supplement | – |
Primary outcome
Safety and tolerability of IV ascorbic acid (IVAA) in target dose of 1500 mg/kg supplementing cytotoxic chemotherapeutic drugs. Standard adverse effect criteria will be used.
Time frame: At every clinic visit
Observe for qualitative indicators that IV ascorbic acid mitigates chemotherapy adverse effects
Time frame: Every treatment cycle
3 secondary outcomes
To monitor for disease arrest or response (RECIST criteria) in a population in which arrest or response is unusual or rare
Time frame: CT assessment every 2 months
Quality of life assessment using FACT B and POMS R
Time frame: every month
Measure the effect of chemotherapy on pharmacokinetics of intravenous ascorbic acid
Time frame: Before and 5 days following first chemotherapy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2013.
- Derived from this study: PubMed 25848948Hoffer LJ, Robitaille L, Zakarian R, Melnychuk D, Kavan P, Agulnik J, Cohen V, Small D, Miller WH Jr. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial. PLoS One. 2015 Apr 7;10(4):e0120228. doi: 10.1371/journal.pone.0120228. eCollection 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Leonard John Hoffer, MD PhD principal investigator
Faculty of Medicine, McGill University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing vitamin C (ascorbic acid) in people with Cancer, run by Jewish General Hospital at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability of IV ascorbic acid (IVAA) in target dose of 1500 mg/kg supplementing cytotoxic chemotherapeutic drugs. Standard adverse effect criteria will be used. (time frame: At every clinic visit). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01050621, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2013.