Ovarian Carcinoma, Stage 3 or 4Phase 1NCT01138137
N-acetylcysteine Given IV With Cisplatin and Paclitaxel in Patients With Ovarian Cancer
A Phase 1 study testing Paclitaxel, N-acetylcysteine and Cisplatin in people with Ovarian Carcinoma, Stage 3 or 4 and Epithelial Ovarian Carcinoma, run by OHSU Knight Cancer Institute at 1 site in United States.
Trial summary
RATIONAL FOR STUDYING IV NAC AS POTENTIAL CHEMOPROTECTANT: Cisplatin has shown efficacy in the treatment of subjects with epithelial ovarian cancer. Systemic toxicities associated with cisplatin include nephro, oto, and nerve toxicities. Read more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- Ovarian Carcinoma, Stage 3 or 4, Epithelial Ovarian Carcinoma, Primary Peritoneal Carcinoma
- What is being tested?
- Paclitaxel, N-acetylcysteine and Cisplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2010to Dec 2014
- Phase
- Phase 1
- 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 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed written informed consent in accordance with institutional guidelines
- Histologically confirmed diagnosis of stage 3 or 4 epithelial ovarian or primary peritoneal carcinoma
- Have had debulking surgery with optimal tumor cytoreduction
- Standard treatment offered for ovarian cancer including systemic or intraperitoneal cisplatin with systemic taxane-based chemotherapy
- Age ≥ 18 years to ≤ 75 years
- Laboratory testing within 14 days of registration:
Show all 14Show fewer
- White blood cell count ≥ 2.5 x 103/mm3
- Absolute granulocyte count ≥ 1.2 x 103/mm3
- Platelets ≥ 100 x 103/mm3
- Creatinine < 1.8
- Bilirubin < 2.0
- Serum glutamate oxaloacetate transaminase (SGOT)/Serum glutamate pyruvate transaminase (SGPT) < 2.5 x institutional upper limits of normal
- Performance status must be Eastern Cooperative Oncology Group (ECOG) < 2 (Karnofsky ≥ 50)
- Life expectancy of ≥ 60 days from the date of registration
Who cannot join
- Pregnant, positive beta human chorionic gonadotropin (hCG), or lactating
- History of clinically significant reactive airway disease
- Active significant cardiac disease as evidenced by New York Heart Association Classification for chronic heart failure (CHF), Class III or IV
- Uncontrolled (over the last 30 days) clinically significant confounding medical conditions
- Allergies or other contraindications to IP cisplatin, IV Taxol, or IV NAC.
Trial locations and contacts
1 site in 1 country.
United States1 site
Oregon Health & Science University
Portland, Oregon, 97239
About this study
Official title: Phase I Dose Escalation Study of N-acetylcysteine (NAC) Administered Intravenously (IV) in Conjunction With Intraperitoneal (IP) Administered Cisplatin and IV/IP Paclitaxel in Patients With Stage III or IV Ovarian Cancer
RATIONAL FOR STUDYING IV NAC AS POTENTIAL CHEMOPROTECTANT:
Cisplatin has shown efficacy in the treatment of subjects with epithelial ovarian cancer. Systemic toxicities associated with cisplatin include nephro, oto, and nerve toxicities. It may be possible to reduce the toxicities of cisplatin by administering it in conjunction with IV NAC. NAC may reduce cisplatin related nephro, oto, and nerve toxicities without compromising the effectiveness of the chemotherapy against the ovarian cancer cells. It is possible that this combination of drugs may in the future allow ovarian cancer patients to receive the full series of IP cisplatin-paclitaxel chemotherapy, with fewer side effects and improved survival.
It is hypothesized that the proposed treatment of stage III or IV epithelial ovarian cancer with IP cisplatin and IV/IP paclitaxel in conjunction with IV NAC will limit the neurotoxicity, nephrotoxicity and ototoxicity that is associated with cisplatin administration.
Read the detailed description
OBJECTIVES:
PRIMARY:
To determine the Maximum Tolerated Dose (MTD) and assess the toxicity of IV NAC in conjunction with IP cisplatin and IV/IP paclitaxel in subjects with stage 3 or 4 epithelial ovarian cancer that has been surgically debulked
SECONDARY:
- To describe tumor response in subjects receiving treatment for previously debulked stage 3 or 4 epithelial ovarian cancer with IP cisplatin, IV/IP paclitaxel , and IV NAC.
- To describe the incidence and severity of nephrotoxicity (Creatinine Clearance (CrCl)) in subjects undergoing treatment for stage 3 or 4 epithelial ovarian cancer with IP cisplatin, IV paclitaxel and IV NAC and who have had their disease surgically debulked.
- To describe the incidence and severity of hearing loss in subjects undergoing treatment for stage 3 or 4 epithelial ovarian cancer with IP cisplatin, IV/IP paclitaxel and IV NAC and who have had their disease surgically debulked.
- To describe the incidence and severity of peripheral and autonomic neuropathy in subjects undergoing treatment for stage 3 or 4 epithelial ovarian cancer with IP cisplatin, IV/IP Taxol and IV NAC and who have had their disease surgically debulked.
OUTLINE:
Subjects will undergo chemotherapy for epithelial ovarian cancer with paclitaxel IV, 135 mg/m2 (Day 1) and IP cisplatin 100 mg/m2 (Day2), followed by Taxol IP, 60 mg/m2 (Day 8) every 3 weeks for 6 courses. Sixty minutes prior to each course of IP cisplatin, IV NAC (starting at 150 mg/kg) will be infused over 30 minutes. A dose escalation schema for NAC will be followed. Toxicity to the therapy will be graded according to the Common Terminology Criteria for Adverse Events.
- Conditions
- Ovarian Carcinoma, Stage 3 or 4, Epithelial Ovarian Carcinoma, Primary Peritoneal Carcinoma
- Being tested
- Paclitaxel, N-acetylcysteine, Cisplatin
- Keywords
- ovarian cancer, epithelial ovarian cancer, peritoneal cancer
- Medical subject headings
- Ovarian Neoplasms, Carcinoma, Ovarian Epithelial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PaclitaxelDrug
Dose: 135mg/m2 infused IV on Day 1 of 3 week cycle
Dose: 60mg/m2 infused IP on Day 8 of 3 week cycle
6 treatment cycles
N-acetylcysteineDrug
Also called NAC
A group of 5 subjects will be evaluated at each dose level.
On Day 2 of each 3 week cycle, subject receives IV NAC followed by IP cisplatin.
6 treatment cycles
Dose escalation schema:
Level 1: 150mg/kg
Level 2: 300mg/kg
Level 3: 600mg/kg
Level 4: 800mg/kg
Level 5: 1000mg/kg
Level 6: 1200mg/kg
CisplatinDrug
Dose: 100mg/m2 infused IP on day 2 of each 3 week cycle 60 min after the NAC infusion
6 treatment cycles
| Study group | Role | What they receive |
|---|---|---|
| All subjects | Experimental | Not described Receives: Drug: Paclitaxel; Drug: N-acetylcysteine; Drug: Cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the MTD and assess the toxicity of IV NAC
The MTD of IV NAC will be defined as one dose level below that which produces NCI Common Toxicity Criteria (CTC) grade 3 or 4 non-hematologic toxicity in 20% of subjects. The toxicity of NAC can be differentiated from that of the chemotherapeutic drugs as the half-life of NAC is very short and adverse effects are seen either during or very soon after the administration of NAC.
Measured: 4 years
Secondary outcomes (4)
To describe tumor response
Measured: 4 years
To describe the incidence and severity of nephrotoxicity
Measured: 4 years
To describe the incidence and severity of hearing loss
Measured: 4 years
To describe the incidence and severity of peripheral and autonomic neuropathy
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2010 (estimated)
- Study startJun 2010
- Primary completionDec 2014
- Study completionDec 2014
Why it stopped: No funding was available for the cost of the IV N-acetylcysteine (NAC).
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ovarian Carcinoma, Stage 3 or 4Studies of the same condition, open and under way.
- More trials run by OHSU Knight Cancer InstituteThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- OHSU Knight Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Edward Neuwelt, OHSU Knight Cancer Institute
- Investigators
- Edward A Neuwelt, MD, Principal investigator, Knight Cancer Institute at Oregon Health & Science University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01138137
- Sponsor's protocol ID
- IRB00004229
- Other IDs
- 4229, SOL-08005-L, OHSU-4229
- Status last verified
- Apr 2017
- First submitted
- 3 Jun 2010
- Last updated
- 21 Apr 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Dose Escalation Study of N-acetylcysteine (NAC) Administered Intravenously (IV) in Conjunction With Intraperitoneal (IP) Administered Cisplatin and IV/IP Paclitaxel in Patients With Stage III or IV Ovarian Cancer
- ClinicalTrials.gov ID
- NCT01138137
- Acronym / sponsor ID
- IRB00004229
- Conditions
- Ovarian Carcinoma, Stage 3 or 4, Epithelial Ovarian Carcinoma, Primary Peritoneal Carcinoma
- Keywords
- ovarian cancer, epithelial ovarian cancer, peritoneal cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No funding was available for the cost of the IV N-acetylcysteine (NAC).
- Enrolment
- 0 participants (actual)
- Lead sponsor
- OHSU Knight Cancer InstituteUniversity, hospital or other
- Study start
- Jun 2010
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 7 Jun 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.
RATIONAL FOR STUDYING IV NAC AS POTENTIAL CHEMOPROTECTANT:
Cisplatin has shown efficacy in the treatment of subjects with epithelial ovarian cancer. Systemic toxicities associated with cisplatin include nephro, oto, and nerve toxicities. It may be possible to reduce the toxicities of cisplatin by administering it in conjunction with IV NAC. NAC may reduce cisplatin related nephro, oto, and nerve toxicities without compromising the effectiveness of the chemotherapy against the ovarian cancer cells. It is possible that this combination of drugs may in the future allow ovarian cancer patients to receive the full series of IP cisplatin-paclitaxel chemotherapy, with fewer side effects and improved survival.
It is hypothesized that the proposed treatment of stage III or IV epithelial ovarian cancer with IP cisplatin and IV/IP paclitaxel in conjunction with IV NAC will limit the neurotoxicity, nephrotoxicity and ototoxicity that is associated with cisplatin administration.
Detailed description
OBJECTIVES:
PRIMARY:
To determine the Maximum Tolerated Dose (MTD) and assess the toxicity of IV NAC in conjunction with IP cisplatin and IV/IP paclitaxel in subjects with stage 3 or 4 epithelial ovarian cancer that has been surgically debulked
SECONDARY:
- To describe tumor response in subjects receiving treatment for previously debulked stage 3 or 4 epithelial ovarian cancer with IP cisplatin, IV/IP paclitaxel , and IV NAC.
- To describe the incidence and severity of nephrotoxicity (Creatinine Clearance (CrCl)) in subjects undergoing treatment for stage 3 or 4 epithelial ovarian cancer with IP cisplatin, IV paclitaxel and IV NAC and who have had their disease surgically debulked.
- To describe the incidence and severity of hearing loss in subjects undergoing treatment for stage 3 or 4 epithelial ovarian cancer with IP cisplatin, IV/IP paclitaxel and IV NAC and who have had their disease surgically debulked.
- To describe the incidence and severity of peripheral and autonomic neuropathy in subjects undergoing treatment for stage 3 or 4 epithelial ovarian cancer with IP cisplatin, IV/IP Taxol and IV NAC and who have had their disease surgically debulked.
OUTLINE:
Subjects will undergo chemotherapy for epithelial ovarian cancer with paclitaxel IV, 135 mg/m2 (Day 1) and IP cisplatin 100 mg/m2 (Day2), followed by Taxol IP, 60 mg/m2 (Day 8) every 3 weeks for 6 courses. Sixty minutes prior to each course of IP cisplatin, IV NAC (starting at 150 mg/kg) will be infused over 30 minutes. A dose escalation schema for NAC will be followed. Toxicity to the therapy will be graded according to the Common Terminology Criteria for Adverse Events.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All subjects | Experimental | Drug: Paclitaxel, Drug: N-acetylcysteine, Drug: Cisplatin |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Signed written informed consent in accordance with institutional guidelines
- Histologically confirmed diagnosis of stage 3 or 4 epithelial ovarian or primary peritoneal carcinoma
- Have had debulking surgery with optimal tumor cytoreduction
- Standard treatment offered for ovarian cancer including systemic or intraperitoneal cisplatin with systemic taxane-based chemotherapy
- Age ≥ 18 years to ≤ 75 years
Key exclusion criteria (5 listed)
- Pregnant, positive beta human chorionic gonadotropin (hCG), or lactating
- History of clinically significant reactive airway disease
- Active significant cardiac disease as evidenced by New York Heart Association Classification for chronic heart failure (CHF), Class III or IV
- Uncontrolled (over the last 30 days) clinically significant confounding medical conditions
- Allergies or other contraindications to IP cisplatin, IV Taxol, or IV NAC.
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 |
|---|---|---|
| PaclitaxelDose: 135mg/m2 infused IV on Day 1 of 3 week cycle Dose: 60mg/m2 infused IP on Day 8 of 3 week cycle 6 treatment cycles | Drug | All subjects |
| N-acetylcysteineAlso: NACA group of 5 subjects will be evaluated at each dose level. On Day 2 of each 3 week cycle, subject receives IV NAC followed by IP cisplatin. 6 treatment cycles Dose escalation schema: Level 1: 150mg/kg Level 2: 300mg/kg Level 3: 600mg/kg Level 4: 800mg/kg Level 5: 1000mg/kg Level 6: 1200mg/kg | Drug | All subjects |
| CisplatinDose: 100mg/m2 infused IP on day 2 of each 3 week cycle 60 min after the NAC infusion 6 treatment cycles | Drug | All subjects |
Primary outcome
To determine the MTD and assess the toxicity of IV NAC
Time frame: 4 years
The MTD of IV NAC will be defined as one dose level below that which produces NCI Common Toxicity Criteria (CTC) grade 3 or 4 non-hematologic toxicity in 20% of subjects. The toxicity of NAC can be differentiated from that of the chemotherapeutic drugs as the half-life of NAC is very short and adverse effects are seen either during or very soon after the administration of NAC.
4 secondary outcomes
To describe tumor response
Time frame: 4 years
To describe the incidence and severity of nephrotoxicity
Time frame: 4 years
To describe the incidence and severity of hearing loss
Time frame: 4 years
To describe the incidence and severity of peripheral and autonomic neuropathy
Time frame: 4 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2017.
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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.
Edward A Neuwelt, MD principal investigator
Knight Cancer Institute at Oregon Health & Science 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 study testing Paclitaxel, N-acetylcysteine and Cisplatin in people with Ovarian Carcinoma, Stage 3 or 4 and Epithelial Ovarian Carcinoma, run by OHSU Knight Cancer Institute at 1 site in United States.
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 14 inclusion and 5 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: withdrawn, as of the sponsor's last update on 21 Apr 2017. 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 United States. 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 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.
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 was withdrawn before enrolling participants, so there are no results.
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?
To determine the MTD and assess the toxicity of IV NAC (time frame: 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Apr 2017.