Lapatinib and Topotecan in Treating Patients With Ovarian Epithelial Cancer or Primary Peritoneal Cancer That Did Not Respond to Cisplatin or Carboplatin

NCT00436644 | Completed Phase 2 Results DMC

• 3 other identifiers: RC0661P30CA01508306-002426
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

Brief Summary

RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving lapatinib together with topotecan may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving lapatinib together with topotecan works in treating patients with ovarian epithelial cancer or primary peritoneal cancer that did not respond to cisplatin or carboplatin.

Conditions

Ovarian Cancer; Peritoneal Cavity Cancer

Keywords

recurrent ovarian epithelial cancer; peritoneal cavity cancer

Outcome Measures

Primary Outcomes (1)

• Response Rate (Complete Response (CR) or Partial Response (PR))

  Measurable disease patients: measureable disease is defined as at least one lesion whose longest diameter \>= 2cm with conventional techniques or \>=1cm with spiral CT * Confirmed tumor response (complete and partial) as measured by RECIST(Response Evaluation Criteria In Solid Tumors) criteria on 2 consecutive evaluations at least 4 weeks apart. * Confirmed tumor response is at least a 30% decrease in the sum of the longest diameter of target lesions and no new lesions. Non-measurable disease patients: * Decrement in CA125 by \> 50% * Improvement in other evaluable disease

  Two consecutive evaluations at least 4 weeks apart

Secondary Outcomes (3)

• Time to Progression

  Time from registration to progression (up to 2 years)

• Adverse Event Profile

  Every 4 weeks

• Overall Survival

  Time from Registration to Death or last follow-up (up to 3 years)

Study Arms (1)

Lapatinib + Topotecan

EXPERIMENTAL

Assess biological effects of topotecan and lapatinib in patients with epithelial ovarian cancer and primary peritoneal carcinoma.

Drug: Lapatinib; Drug: Topotecan

Interventions

Lapatinib DRUG

1250 mg orally days 1 -28.

Also known as: Tykerb

Lapatinib + Topotecan

Topotecan DRUG

3.2 mg/m2 IV over 30 min in 100mL D5W (5% dextrose in water) or 0.9% NS at days 1, 8 \& 15.

Also known as: Hycamptin

Lapatinib + Topotecan

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed ovarian epithelial or primary peritoneal carcinoma * Must have one of the following: * Measurable disease * Evaluable disease AND a CA-125 value that has increased ≥ 2 times the nadir value established after debulking surgery and first-line chemotherapy, confirmed by a second measurement within the past 21 days * If a second measurement has not been done, it can be done ≥ 7 days but \< 21 days prior to study treatment * Platinum-refractory and/or -resistant disease after first-line chemotherapy * Patients retreated with platinum agents (i.e., second relapse) are not eligible * Patients treated with first-line triplet therapy (e.g., on clinical trial GOG-182) are eligible * Must have had debulking surgery * Tissue blocks from this surgery must be available * No CNS metastases PATIENT CHARACTERISTICS: * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Life expectancy ≥ 12 weeks * Absolute neutrophil count ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * AST ≤ 3 times ULN (5 times ULN if there is liver involvement) * Creatinine ≤ 1.5 times ULN * Hemoglobin ≥ 9.0 g/dL * No uncontrolled infection * No New York Heart Association class III or IV heart failure * Left Ventricular Ejection Fraction (LVEF) ≥ 50% by echocardiogram * No seizure disorder * No other prior or concurrent malignancy in the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior topotecan hydrochloride * More than 4 weeks since prior surgery or procedure involving the peritoneum or pleura * CA125 measurements used as basis for enrollment must be made outside of this 4-week window * More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered * More than 4 weeks since prior immunotherapy * More than 4 weeks since prior biologic therapy * More than 4 weeks since prior radiotherapy * No prior radiotherapy to \> 25 % of bone marrow * No prior therapy with an anti-epidermal growth factor receptor or anti-HER2 tyrosine kinase inhibitors * No prior agents targeting topoisomerase I * No prior or concurrent human anti-mouse antibodies (HAMA) in patients with non-measurable disease * At least 14 days since prior and no concurrent herbal or dietary supplements * Vitamin supplements are allowed unless they include herbal additives * At least 14 days since prior and no concurrent CYP3A4 inducers, including any of the following: * Rifampin * Rifabutin * Rifapentine * Phenytoin * Carbamazepine * Phenobarbital * Efavirenz * Nevirapine * Cortisone (\> 50 mg) * Hydrocortisone (\> 40 mg) * Prednisone (\> 10 mg) * Methylprednisolone (\> 8 mg) * Dexamethasone (\> 1.5 mg) * Oral doses of ≤ 1.6 mg of dexamethasone allowed * Modafinil * Hypericum perforatum (St. John's wort) * At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following: * Clarithromycin * Erythromycin * Troleandomycin * Itraconazole * Ketoconazole * Fluconazole (\> 150 mg daily) * Voriconazole * Delaviridine * Nelfinavir * Amprenavir * Ritonavir * Indinavir * Saquinavir * Lopinavir * Verapamil * Diltiazem * Nefazodone * Fluvoxamine * Cimetidine * Aprepitant * Grapefruit or grapefruit juice * At least 6 months since prior and no concurrent amiodarone * No concurrent participation in another study involving a pharmacologic agent (e.g., drugs, biologics, immunotherapy, gene therapy) for symptom control or therapeutic intent

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Mayo Clinic Arizona

Scottsdale, Arizona, 85254, United States

Location

Mayo Clinic in Jacksonville

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Carcinoma, Ovarian Epithelial

Interventions

Lapatinib; Topotecan

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids

Results Point of Contact

• Title: Dr. Paul Haluska
• Organization: Mayo Clinic

haluska.paul@mayo.edu

507-266-2123

Study Officials

• Paul Haluska, MD, PhD

  Mayo Clinic

  STUDY CHAIR

• John K. Camoriano, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Candido E. Rivera, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 15, 2007
• First Posted: February 19, 2007
• Study Start: March 1, 2007
• Primary Completion: March 1, 2009
• Study Completion: November 1, 2012
• Last Updated: April 16, 2014
• Results First Posted: March 22, 2012

Record last verified: 2014-03

Locations

US (3)