Clinical trial NCT01831089: Phase I Study of Lurbinectedin (PM01183) in Combination With Paclitaxel, With or Without Bevacizumab, in Selected Advanced Solid Tumors
Official title: Phase I Multicenter, Open-label, Clinical and Pharmacokinetic Study of Lurbinectedin (PM01183) in Combination With Weekly Paclitaxel, With or Without Bevacizumab, in Patients With Selected Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Ovarian Cancer
Gynecological Cancer
Head and Neck Carcinoma
Non-small Cell Lung Cancer
Small Cell Lung Cancer
Non-squamous Cell Lung Cancer
Lead sponsor: PharmaMar
Sponsor class: INDUSTRY
First posted: 2013-04-15
Enrollment: 69
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: Clinical trial of PM01183 in combination with paclitaxel, with or without bevacizumab, in patients with solid tumors

Detailed description: Clinical trial to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of PM01183 in combination with weekly paclitaxel, with or without bevacizumab. Once a recommended dose is defined for the PM01183 and weekly paclitaxel combination, the feasibility of adding bevacizumab to this combination will be explored in a selected cohort of patients to characterize the safety profile and feasibility of this combination, to obtain preliminary information on antitumor activity, to obtain preliminary information on quality of life (QoL), to characterize the pharmacokinetics (PK) of this combination and to detect major drug-drug PK interactions and PK(pharmacokinetic)/PD(pharmacodynamic) correlation and to conduct an exploratory pharmacogenomic(PGx) analysis in patients with selected advanced solid tumors.

Eligibility criteria: Inclusion Criteria:

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

  1. Breast cancer
  2. Epithelial ovarian cancer or gynecological cancer
  3. Head and neck squamous cell carcinoma
  4. Non-small cell lung cancer
  5. Small cell lung cancer
  6. Platinum-refractory germ-cell tumors.
  7. Adenocarcinoma or carcinoma of unknown primary site
* Adequate bone marrow, renal, hepatic, and metabolic function
* Recovery to grade ≤ 1 or to baseline from any Adverse Event (AE) derived from previous treatment (excluding alopecia of any grade).
* Pre-menopausal women must have a negative pregnancy test before study entry and agree to use a medically acceptable method of contraception throughout the treatment period and for at least six weeks after treatment discontinuation

Exclusion Criteria:

* Prior treatment with PM01183 or weekly paclitaxel or nanoalbumin-paclitaxel
* Patients who have previously discontinued paclitaxel-based regimes due to drug related toxicity.
* Known hypersensitivity to bevacizumab or any component of its formulation
* Patients who have previously discontinued bevacizumab-containing regimes due to drug-related toxicity.
* More than three prior lines of chemotherapy
* Less than three months since last taxane-containing therapy.
* Wash-out period:

  1. Less than three weeks since the last chemotherapy-containing regimen
  2. Less than three weeks since the last radiotherapy dose
  3. Less than four weeks since last monoclonal antibody-containing therapy
* Concomitant diseases/conditions:

Unstable angina, myocardial infarction, valvular heart disease, encephalopathy, ischemic attacks, hemorrhagic or ischemic cerebrovascular accident (CVA) or ongoing pulmonary embolism within last year, arrhythmia, hepatopathy, uncontrolled infection, hemoptysis or oxygen requiring dyspnea, known HIV infection, bleeding risk, muscular problems, peripheral neuropathy, Symptomatic or progressive brain metastases or leptomeningeal disease.

* Men or pre-menopausal women who are not using an effective method of contraception as previously described; actively breast feeding women.
* Patients who have pelvic irradiation with doses ≥ 45 Grays (Gy).
* History of previous bone marrow and/or stem cell transplantation.
* Confirmed bone marrow involvement

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: The MTD was followed mainly during Cycle 1 through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (cycle duration: 3 weeks)
measure: Recommended Dose (RD)
timeFrame: The RD was followed mainly during Cycle 1 through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (cycle duration: 3 weeks)
measure: Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
timeFrame: DLT was followed mainly during Cycle 1 through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (cycle duration: 3 weeks)
Secondary outcomes:
measure: Best Tumor Response
timeFrame: Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks)
measure: Progression-free Survival
timeFrame: Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks)
measure: Duration of Response (DR)
timeFrame: Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks)
measure: Quality of Life (QoL)
timeFrame: Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks)
Other outcomes:
Locations:
city: New York
country: United States
state: New York
city: Madrid
country: Spain
city: Bellinzona
country: Switzerland
Study officials:
References: