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Phase I Trial Of Cisplatin And KML-001 In Advanced Non-Small Cell Lung Cancer and Other Platinum Responsive Malignancies

Phase 1
18 Years
Open (Enrolling)
Non-Small Cell Lung Cancer, Small Cell Lung Cancer, Platinum Responsive Malignancies

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Trial Information

Phase I Trial Of Cisplatin And KML-001 In Advanced Non-Small Cell Lung Cancer and Other Platinum Responsive Malignancies

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 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

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 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.

Inclusion Criteria:

- 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 metastases which are symptomatic must have
received therapy (surgery, 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

- 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.

- 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

- 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.

Exclusion Criteria:

- 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:

1. Current uncontrolled cardiac disease;

2. Corrected (Bazett) QTc interval of > .50 ms (male) or > .52 ms (female);

3. Acute bacterial or fungal infection requiring intravenous antibiotics at the
time of registration;

4. Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy within 4 weeks of

5. Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;

6. Patients with acquired Immune Deficiency Syndrome (AIDS) based upon current 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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the maximum tolerated dose of KML001 in combination with cisplatin

Outcome Time Frame:

When dose limiting toxicities are established

Safety Issue:


Principal Investigator

Martin Edelman, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Maryland


United States: Food and Drug Administration

Study ID:




Start Date:

May 2010

Completion Date:

December 2013

Related Keywords:

  • Non-Small Cell Lung Cancer, Small Cell Lung Cancer
  • Platinum Responsive Malignancies
  • non small cell lung cancer
  • small cell lung cancer
  • Platinum Responsive
  • solid tumor malignancies
  • Neoplasms
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms
  • Small Cell Lung Carcinoma



University of Maryland Greenebaum Cancer Center Baltimore, Maryland  21201