Clinical trial NCT01970553: Escalating Doses of PM01183 in Combination With Gemcitabine in Patients With Specific Unresectable Solid Tumors
Official title: Phase I Multicenter, Open-label, Clinical and Pharmacokinetic Study of PM01183 in Combination With Gemcitabine in Non-heavily Pretreated Patients With Selected Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Specific Advanced Solid Tumors
Keywords: lurbinectedin
PM01183
tumors
cancer
Pharma Mar
Lead sponsor: PharmaMar
Sponsor class: INDUSTRY
First posted: 2013-10-28
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase I multicenter, open-label, clinical and pharmacokinetic study of PM01183 in combination with gemcitabine in non-heavily pretreated patients with selected advanced solid tumors to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of PM01183 in combination with gemcitabine, to characterize the safety profile and feasibility of this combination in patients with selected advanced solid tumors, to characterize the pharmacokinetics (PK), to obtain preliminary information on the clinical antitumor activity in non-heavily pretreated selected solid tumor patients and to evaluate the pharmacogenomics (PGx) in tumor samples of patients exposed, in order to assess potential markers of response and/or resistance.


Eligibility criteria: Inclusion Criteria:

* Voluntarily written informed consent
* Age: between 18 and 75 years (both inclusive)
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1
* Life expectancy ≥ 3 months
* Patients with a histologically/cytologically confirmed diagnosis of advanced disease of any of the following tumors:

  1. Breast cancer
  2. Epithelial ovarian cancer (including primary peritoneal disease and/or fallopian tube carcinomas and/or endometrial adenocarcinomas)
  3. Stromal uterine sarcomas
  4. Non-small cell lung cancer (NSCLC)
  5. Platinum-refractory or relapsed germ cell tumors
  6. Adenocarcinoma of the exocrine pancreas
  7. Biliary tract adenocarcinoma
  8. Adenocarcinoma or carcinoma of unknown primary site
  9. Advanced or unresectable mesothelioma
* At least three weeks since the last anticancer therapy,including radiation therapy (RT)
* Adequate bone marrow, renal, hepatic, and metabolic function
* Left ventricular ejection fraction (LVEF) by echocardiography (ECHO) or multiple-gated acquisition (MUGA) within normal range (according to institutional standards).
* Women of childbearing potential must have a negative serum pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for six weeks after discontinuation of treatment.

Exclusion Criteria:

* Concomitant diseases/conditions:

  * History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within last year.
  * Symptomatic or any uncontrolled arrhythmia
  * Ongoing chronic alcohol consumption, or cirrhosis
  * Active uncontrolled infection.
  * Known human immunodeficiency virus (HIV) infection.
  * Any other major illness that, in the Investigator's judgment
* Brain metastases or leptomeningeal disease involvement
* Men or women of childbearing potential who are not using an effective method of contraception
* Patients who have had radiation therapy in more than 35% of the bone marrow
* History of previous bone marrow and/or stem cell transplantation
* Prior treatment with gemcitabine-containing therapy for advanced disease

Primary outcomes:
measure: Recommended Dose (RD)
timeFrame: 19 months
Secondary outcomes:
measure: Pharmacokinetics (PK) characterisation
timeFrame: 19 months
measure: Preliminary antitumor efficacy
timeFrame: 29 months
measure: Pharmacogenomics (PGx)
timeFrame: 29 months
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital Universitario Madrid Sanchinarro
city: Seville
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: London
country: United Kingdom
facility: University College of London Hospital
Study officials:
affiliation: Pharma Mar
name: Sergio Szyldergemajn, MD
role: STUDY_CHAIR
References: