Non-Small Cell Lung Cancer, Small Cell Lung CancerPhase 10805GCCNCT01110226
Trial Of Cisplatin And KML-001 in Platinum Responsive Malignancies
A Phase 1 study testing KML-001 and Cisplatin in people with Non-Small Cell Lung Cancer, Small Cell Lung Cancer and Platinum Responsive Malignancies, run by University of Maryland, Baltimore at 1 site in United States.
Trial summary
This is a Phase I Clinical Trial. Phase I studies are designed to determine the amount of investigational drugs that can be safely tolerated and to define the side effects that limit the dose. The drug administered in this study is KML-001. It is a highly soluble, orally available arsenic agent. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer, Small Cell Lung Cancer, Platinum Responsive Malignancies
- What is being tested?
- KML-001 and Cisplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Apr 2010to 27 Oct 2015
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed non-small cell lung cancer or other "platinum responsive malignancies" , including but not limited to: esophageal cancer, ovarian cancer, germ cell malignancies , transitional cell cancer etc. that are not curable with chemotherapy, surgery or radiotherapy. A tissue block or fresh tissue biopsy is required. Patients with CNS (Central Nervous System) metastases which are symptomatic must have received therapy (surgery, X Ray Therapy (XRT), gamma knife) and be neurologically stable and off steroids. Patients with asymptomatic lesions without significant edema and no evidence of shift are allowed to participate without prior CNS therapy. Such patients are anticipated to receive specific CNS therapy after 2-4 courses of therapy.
- Patients may have received prior systemic chemotherapy or radiation therapy. At least 2 weeks should have elapsed since the last treatment and patients should have recovered from previous significant toxicity (i.e. to grade 1 or less). Alopecia, skin discoloration etc. are not considered significant toxicities. There is no limit on the number of prior therapies. Patients may have received prior cisplatin or other platinum regimens.
- Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2.
- Patient 18 years of age or older.
- Absolute Granulocyte Count greater than or equal to 1.5 x 10^9
- Platelet count greater than or equal to 100 x 10^9
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- Serum creatinine within normal limits, or an estimated or measured creatinine clearance greater than or equal to 65 ml/min.
- All patients must be informed of the investigational nature of this study and must sign and give written informed consent.
- Serum calcium, magnesium and potassium must be within normal limits.
Who cannot join
- Patients must not have serious infection or other serious underlying medical condition which would impair the ability of the patient to receive protocol treatment. These need not be specified in the history and physical and can be documented through signature on the eligibility checklist. Severe, active co-morbidity, defined as follows:
- Current uncontrolled cardiac disease;
- Corrected (Bazett) QTc interval of > .50 ms (male) or > .52 ms (female);
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
- Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 4 weeks of registration;
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
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- Patients with acquired Immune Deficiency Syndrome (AIDS) based upon current Center for Disease Control (CDC) definition or patients known to be HIV positive.
- Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception.
- Pre-existing ≥ grade 2 peripheral neuropathy.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, 21201
About this study
Official title: Phase I Trial Of Cisplatin And KML-001 In Advanced Non-Small Cell Lung Cancer and Other Platinum Responsive Malignancies
This is a Phase I Clinical Trial. Phase I studies are designed to determine the amount of investigational drugs that can be safely tolerated and to define the side effects that limit the dose. The drug administered in this study is KML-001. It is a highly soluble, orally available arsenic agent. It is currently being tested to determine its effects on telomerase activity.
In other words, the purpose of this research study is to find the highest dose of KML001, that can be given without causing severe side effects when it is combined with a standard, commercially available anti-cancer drug called cisplatin.
Read the detailed description
Telomerase is the enzyme synthesizing the specific DNA sequences found at the telomeres in the body's chromosomes. It is thus responsible for maintaining the length of telomeres. Telomerase has been detected in human cancer cells and is found to be 10-20 times more active than in normal body cells. This provides a selective growth advantage to many types of tumors. If telomerase activity was to be turned off, then telomeres in cancer cells would shorten, just like they do in normal body cells. This would prevent the cancer cells from dividing uncontrollably in their early stages of development. In the event that a tumor has already thoroughly developed, it may be removed and anti-telomerase therapy could be administered to prevent relapse.
This study is being offered to patients with advanced cancer which has either no standard therapy or which has progressed after treatment with one or more standard treatments.
The primary objective of this study :
To determine the maximum tolerated dose of KML001 in combination with cisplatin in patients with advanced malignancy. This objective has been met. The study will be reopened with expansion cohorts in advanced small cell lung cancer and non-small cell lung cancer to better assess the activity of the combination, pending (Institutional Review Board (IRB) approval.
Secondary Objectives of the study:
To determine the pharmacokinetics of KML001 and cisplatin in this combination. To assess the response rate, disease-free survival and survival associated with this regimen.
To correlate indications of patient benefit (response or stable disease) with pretreatment specimens
The highest safest doses are determined by increasing the doses of cisplatin and KML001 in successive groups of patients until at least some of them have serious side effects. All patients on this study will receive the same dose of cisplatin, which is known to have antitumor effects. The doses of KML001 will be increased in successive groups of patients. It is possible that those entering the study early may receive suboptimal doses of KML001. At the end of the study we hope to determine the appropriate dose of the KML001 in combination with cisplatin, learn about its side effects and understand how the body metabolizes the drug.
Laboratory data from the University of Maryland Greenebaum Cancer Center (UMGCC) has demonstrated that the combination of KML001 and cisplatin is synergistic in lung cancer cell lines. Cisplatin is the best established agent for the treatment of lung cancer and most treatment regimens have been established with cisplatin (or its congener, carboplatin). This synergism is particularly interesting given that there is an anti-telomere effect for cisplatin.
- Being tested
- KML-001, Cisplatin
- Keywords
- non small cell lung cancer, small cell lung cancer, Platinum Responsive, solid tumor malignancies
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KML-001Drug
Also called sodium metaarsenite
KML001 will begin given to patients first. It should be taken by mouth immediately prior to cisplatin infusion. Patients will be treated in cohorts of three beginning at 15mg. The Dose will be increased until Maximum Tolerated Dose is established.
KML001 will be administered daily for 14 days of a 21 day cycle. Patients will have one week off.
CisplatinDrug
Cisplatin will be given to all patients at a dose of 75 mg/m2 on day 1 of every 21 day cycle over 30 to 90 minutes through an intravenous infusion immediately after the first dose of KML-001
| Study group | Role | What they receive |
|---|---|---|
| Period 1: KML001 15mg plus Cisplatin 75mg/m2 | Experimental | KML001 15 mg orally daily days 1-14 with cisplatin IV on day1 Receives: Drug: KML-001; Drug: Cisplatin |
| Period 2: KML001 17.5mg plus Cisplatin 75mg/m2 | Experimental | KML001 17.5 mg orally daily days 1-14 with cisplatin IV on day1 Receives: Drug: KML-001; Drug: Cisplatin |
| Period 3: KML001 20mg plus Cisplatin 75mg/m2 | Experimental | KML001 20 mg orally daily days 1-14 with cisplatin IV on day1 Receives: Drug: KML-001; Drug: Cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the maximum tolerated dose of KML001 in combination with cisplatin
Once 3 subjects in a cohort reach a dose limiting toxicity. In this protocol, it took 23 months to determine the dose limiting toxicity.
Measured: DLT to be determined up to 30 days after administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2010 (estimated)
- Study start27 Apr 2010
- Primary completion22 Oct 2015
- Study completion27 Oct 2015
Why it stopped: Toxicity was not felt to be acceptable for further development.
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 Non-Small Cell Lung Cancer, Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Collaborators
- University of Maryland, College Park
- Responsible party
- Sponsor
- Investigators
- Martin Edelman, MD, Principal investigator, University of Maryland, College Park
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01110226
- Sponsor's protocol ID
- HP-00040420
- Other IDs
- GCC 0805
- Acronym
- 0805GCC
- Status last verified
- Mar 2020
- First submitted
- 14 Dec 2009
- Last updated
- 17 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Phatak P, Dai F, Butler M, Nandakumar MP, Gutierrez PL, Edelman MJ, Hendriks H, Burger AM. KML001 cytotoxic activity is associated with its binding to telomeric sequences and telomere erosion in prostate cancer cells. Clin Cancer Res. 2008 Jul 15;14(14):4593-602. doi: 10.1158/1078-0432.CCR-07-4572.
PubMed 18628474
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial Of Cisplatin And KML-001 In Advanced Non-Small Cell Lung Cancer and Other Platinum Responsive Malignancies
- ClinicalTrials.gov ID
- NCT01110226
- Acronym / sponsor ID
- 0805GCC / HP-00040420
- Keywords
- non small cell lung cancer, small cell lung cancer, Platinum Responsive, solid tumor malignancies
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Toxicity was not felt to be acceptable for further development.
- Enrolment
- 23 participants (actual)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Collaborators
- University of Maryland, College Park
- Study start
- 27 Apr 2010 (actual)
- Primary completion
- 22 Oct 2015 (actual)
- Study completion
- 27 Oct 2015 (actual)
- First posted
- 26 Apr 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.
This is a Phase I Clinical Trial. Phase I studies are designed to determine the amount of investigational drugs that can be safely tolerated and to define the side effects that limit the dose. The drug administered in this study is KML-001. It is a highly soluble, orally available arsenic agent. It is currently being tested to determine its effects on telomerase activity.
In other words, the purpose of this research study is to find the highest dose of KML001, that can be given without causing severe side effects when it is combined with a standard, commercially available anti-cancer drug called cisplatin.
Detailed description
Telomerase is the enzyme synthesizing the specific DNA sequences found at the telomeres in the body's chromosomes. It is thus responsible for maintaining the length of telomeres. Telomerase has been detected in human cancer cells and is found to be 10-20 times more active than in normal body cells. This provides a selective growth advantage to many types of tumors. If telomerase activity was to be turned off, then telomeres in cancer cells would shorten, just like they do in normal body cells. This would prevent the cancer cells from dividing uncontrollably in their early stages of development. In the event that a tumor has already thoroughly developed, it may be removed and anti-telomerase therapy could be administered to prevent relapse.
This study is being offered to patients with advanced cancer which has either no standard therapy or which has progressed after treatment with one or more standard treatments.
The primary objective of this study :
To determine the maximum tolerated dose of KML001 in combination with cisplatin in patients with advanced malignancy. This objective has been met. The study will be reopened with expansion cohorts in advanced small cell lung cancer and non-small cell lung cancer to better assess the activity of the combination, pending (Institutional Review Board (IRB) approval.
Secondary Objectives of the study:
To determine the pharmacokinetics of KML001 and cisplatin in this combination. To assess the response rate, disease-free survival and survival associated with this regimen.
To correlate indications of patient benefit (response or stable disease) with pretreatment specimens
The highest safest doses are determined by increasing the doses of cisplatin and KML001 in successive groups of patients until at least some of them have serious side effects. All patients on this study will receive the same dose of cisplatin, which is known to have antitumor effects. The doses of KML001 will be increased in successive groups of patients. It is possible that those entering the study early may receive suboptimal doses of KML001. At the end of the study we hope to determine the appropriate dose of the KML001 in combination with cisplatin, learn about its side effects and understand how the body metabolizes the drug.
Laboratory data from the University of Maryland Greenebaum Cancer Center (UMGCC) has demonstrated that the combination of KML001 and cisplatin is synergistic in lung cancer cell lines. Cisplatin is the best established agent for the treatment of lung cancer and most treatment regimens have been established with cisplatin (or its congener, carboplatin). This synergism is particularly interesting given that there is an anti-telomere effect for cisplatin.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Period 1: KML001 15mg plus Cisplatin 75mg/m2 | Experimental | Drug: KML-001, Drug: CisplatinKML001 15 mg orally daily days 1-14 with cisplatin IV on day1 |
| Period 2: KML001 17.5mg plus Cisplatin 75mg/m2 | Experimental | Drug: KML-001, Drug: CisplatinKML001 17.5 mg orally daily days 1-14 with cisplatin IV on day1 |
| Period 3: KML001 20mg plus Cisplatin 75mg/m2 | Experimental | Drug: KML-001, Drug: CisplatinKML001 20 mg orally daily days 1-14 with cisplatin IV on day1 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histologically or cytologically confirmed non-small cell lung cancer or other "platinum responsive malignancies" , including but not limited to: esophageal cancer, ovarian cancer, germ cell malignancies , transitional cell cancer etc. that are not curable with chemotherapy, surgery or radiotherapy. A tissue block or fresh tissue biopsy is required. Patients with CNS (Central Nervous System) metastases which are symptomatic must have received therapy (surgery, X Ray Therapy (XRT), gamma knife) and be neurologically stable and off steroids. Patients with asymptomatic lesions without significant edema and no evidence of shift are allowed to participate without prior CNS therapy. Such patients are anticipated to receive specific CNS therapy after 2-4 courses of therapy.
- Patients may have received prior systemic chemotherapy or radiation therapy. At least 2 weeks should have elapsed since the last treatment and patients should have recovered from previous significant toxicity (i.e. to grade 1 or less). Alopecia, skin discoloration etc. are not considered significant toxicities. There is no limit on the number of prior therapies. Patients may have received prior cisplatin or other platinum regimens.
- Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2.
- Patient 18 years of age or older.
- Absolute Granulocyte Count greater than or equal to 1.5 x 10^9
Key exclusion criteria (9 listed)
- Patients must not have serious infection or other serious underlying medical condition which would impair the ability of the patient to receive protocol treatment. These need not be specified in the history and physical and can be documented through signature on the eligibility checklist. Severe, active co-morbidity, defined as follows:
- Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception.
- Pre-existing ≥ grade 2 peripheral neuropathy.
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 |
|---|---|---|
| KML-001Also: sodium metaarseniteKML001 will begin given to patients first. It should be taken by mouth immediately prior to cisplatin infusion. Patients will be treated in cohorts of three beginning at 15mg. The Dose will be increased until Maximum Tolerated Dose is established. KML001 will be administered daily for 14 days of a 21 day cycle. Patients will have one week off. | Drug | Period 1: KML001 15mg plus Cisplatin 75mg/m2, Period 2: KML001 17.5mg plus Cisplatin 75mg/m2, Period 3: KML001 20mg plus Cisplatin 75mg/m2 |
| CisplatinCisplatin will be given to all patients at a dose of 75 mg/m2 on day 1 of every 21 day cycle over 30 to 90 minutes through an intravenous infusion immediately after the first dose of KML-001 | Drug | Period 1: KML001 15mg plus Cisplatin 75mg/m2, Period 2: KML001 17.5mg plus Cisplatin 75mg/m2, Period 3: KML001 20mg plus Cisplatin 75mg/m2 |
Primary outcome
To determine the maximum tolerated dose of KML001 in combination with cisplatin
Time frame: DLT to be determined up to 30 days after administration
Once 3 subjects in a cohort reach a dose limiting toxicity. In this protocol, it took 23 months to determine the dose limiting toxicity.
Results and safety
The study was stopped early (reason given: Toxicity was not felt to be acceptable for further development.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2020.
- Results publication: PubMed 18628474Phatak P, Dai F, Butler M, Nandakumar MP, Gutierrez PL, Edelman MJ, Hendriks H, Burger AM. KML001 cytotoxic activity is associated with its binding to telomeric sequences and telomere erosion in prostate cancer cells. Clin Cancer Res. 2008 Jul 15;14(14):4593-602. doi: 10.1158/1078-0432.CCR-07-4572.
- Individual participant dataSharing planned: No
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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.
Martin Edelman, MD principal investigator
University of Maryland, College Park
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 KML-001 and Cisplatin in people with Non-Small Cell Lung Cancer, Small Cell Lung Cancer and Platinum Responsive Malignancies, run by University of Maryland, Baltimore 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 9 inclusion and 9 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: stopped early, as of the sponsor's last update on 17 Mar 2020. 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 stopped early (reason given: Toxicity was not felt to be acceptable for further development.). Results are not available in the source record.
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 maximum tolerated dose of KML001 in combination with cisplatin (time frame: DLT to be determined up to 30 days after administration). 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 NCT01110226, 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 17 Mar 2020.