Phase I Low Dose WART in Combination With Weekly Paclitaxel for Platinum Resistant Ovarian Cancer

NCT02545010 | Unknown Phase 1

• 2 other identifiers: GY01/05/152015/00496
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Epithelial Ovarian Cancer is the most lethal amongst the gynecologic malignancies and is the fifth leading cause of cancer death in women in the United States.1 Despite initial high response rates, 50% to 75% of women who present with advanced disease suffer relapse and require re treatment2.The optimal treatment for platinum resistant ovarian cancer remains hotly debated. Combination chemotherapy is not favored due to its increased toxicity and lack of convincing benefit when compared to single agent chemotherapy.3,4 Recently, the addition of bevacizumab to single agent chemotherapy in the AURELIA study improved progression free survival (PFS) from 3.4 months to 6.7 months. Response rates were also improved from 11.8% versus 27.3% (p= 0 .001).9 Aim: To determine the maximal tolerated dose (MTD) of weekly paclitaxel in combination with LDWART. The recommended phase II dose (RP2D) will be based on the MTD in this Phase I study. Method: This study is designed as a prospective, single arm phase I study with 3+3 with dose de-escalation and cohort expansion. All patients will receive weekly paclitaxel at a pre specified dose of 80 mg/m2, 70 mg/m2, 60mg/m2 or 50 mg/m2 via intravenous infusion according to institution specific standard practices. Cycles of chemotherapy will be administered weekly without interruption on Days 1,8,15,22,29,36 for a total of 6 weekly cycles in combination with LDWART(Fig.1). LDWART will be given at 60 cGy fractions, twice daily for two days, with a minimum of 4 hours inter fraction interval, starting on day 1 of each cycle of weekly paclitaxel for 6 weeks.(Fig.1). Importance of proposed research: The combination of a LDWART with weekly paclitaxel may improve the efficacy of the current standard weekly paclitaxel in platinum resistant ovarian cancer patients. Potential benefits and risks: The combination may improve treatment response. Adding LDWART may increase treatment risks, but these will be monitored closely.

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• Maximal tolerated dose (MTD) of weekly paclitaxel in combination with LDWART

  The maximum tolerated dose (MTD) of weekly paclitaxel and LDWART is defined as the lowest dose cohort of weekly paclitaxel and LDWART where ≥ 2 out of initial 3 or ≥ 2 out of total 6 patients in any cohort develops a DLT

  Up to 6 weeks from initiation of treatment

Secondary Outcomes (3)

• Objective response rate (ORR)

  From the time of their first treatment with weekly paclitaxel and LDWART till 30 days from end of last treatment

• Progression Free Survival (PFS)

  From the time of their first treatment with weekly paclitaxel and LDWART till 1 year from end of last treatmen

• Dose limiting toxicity (DLT)

  From the time of their first treatment with weekly paclitaxel and LDWART till 30 days from end of last treatment

Study Arms (1)

LDWART + paclitaxel

EXPERIMENTAL

All patients will receive weekly paclitaxel at a pre specified dose of 80 mg/m2, 70 mg/m2, 60mg/m2 or 50 mg/m2 via intravenous infusion according to institution specific standard practices. Cycles of chemotherapy will be administered weekly without interruption on Days 1,8,15,22,29,36 for a total of 6 weekly cycles in combination with LDWART. LDWART will be given at 60 cGy fractions, twice daily for two days, with a minimum of 4 hours inter fraction interval, starting on day 1 of each cycle of weekly paclitaxel for 6 weeks.

Drug: Paclitaxel; Radiation: LDWART (Low Dose Whole Abdominal Radiation Therapy)

Interventions

Paclitaxel DRUG

All patients will receive weekly paclitaxel at a pre specified dose of 80 mg/m2, 70 mg/m2, 60mg/m2 or 50 mg/m2 via intravenous infusion according to institution specific standard practices. Cycles of chemotherapy will be administered weekly without interruption on Days 1,8,15,22,29,36 for a total of 6 weekly cycles in combination with LDWART. Post treatment assessments will be conducted starting Day 43. Patients will then continue chemotherapy off trial protocol with weekly paclitaxel without concurrent LDWART starting Day 50 till disease progression, intolerable toxicity, patient refusal or deemed inappropriate to continue treatment by treating physician.

LDWART + paclitaxel

LDWART (Low Dose Whole Abdominal Radiation Therapy) RADIATION

LDWART will be given at 60 cGy fractions, twice daily for two days, with a minimum of 4 hours inter fraction interval, starting on day 1 of each cycle of weekly paclitaxel for 6 weeks. LDWART will not be administered if doses of weekly paclitaxel are withheld for any reason since it functions as a "chemosensitizer". LDWART will be administered together weekly paclitaxel immediately at point of recovery from toxicity and patient is deemed to be able to continue with treatment by investigator.

LDWART + paclitaxel

Eligibility Criteria

• Age: 21 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements.
• Age ≥ 21 years.
• Histologically confirmed and documented epithelial ovarian carcinomas, primary peritoneal carcinomas, or fallopian tube carcinomas.
• Patients must have platinum-resistant disease, (defined as progression within \<6 months from completion of a minimum of 4 platinum therapy cycles. The date should be calculated from the last administered dose of platinum therapy).
• Patients must have evidence of measurable intra abdominal disease at point of screening.
• Patients must have disease that is measurable according to RECIST version 1.1 and assessable according to the GCIG CA-125 criteria and require treatment with chemotherapy within 14 days of screening. Target lesions should not be selected in previously irradiated fields unless there is clear evidence of progression
• Performance status of Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2.
• Life expectancy of ≥12 weeks with standard treatment.
• Absolute neutrophil count ≥1.0 × 109/L
• Platelet count ≥100 × 109/L (without transfusions within 21 days prior to Day 1 of Cycle 1)
• Hemoglobin ≥9 g/dL
• Prothrombin time and partial thromboplastin time within ≤1.5 × upper limit of normal (ULN)
• International normalized ratio ≤1.5 × ULN
• Total bilirubin ≤1.5 × ULN
• Transaminases (aspartate aminotransferase and/or alanine aminotransferase ≤2.5 × ULN (\<5 × ULN if liver metastases)

You may not qualify if:

• General Criteria
• Is a female patient of childbearing potential, defined as a female physiologically capable of becoming pregnant (including a female whose career, lifestyle, or sexual orientation precludes intercourse with a male partner, and females whose partners have been sterilized by vasectomy or other means), unless they are using a highly effective method for birth control throughout the study and for 12 weeks after the end of treatment. Highly effective methods for birth control include the following:
• Total abstinence: This is an acceptable method when this is consistent with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
• Female sterilization: The patient has had a surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks prior to taking study drug. In case of an oophorectomy alone, the reproductive status of the patient must have been confirmed by follow-up hormone level assessment.
• Male partner sterilization: The patient has the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate.
• (For female patients on the study, the vasectomized male partner should be the sole partner for that patient.)
• These patients must also agree to the following:
• Use of a combination of the following (1+2):
• Placement of an intrauterine device or intrauterine system
• Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam, gel, film, or cream, or vaginal suppository Reliable contraception maintained throughout the study and for 12 weeks after study drug discontinuation
• Females considered post-menopausal and not of childbearing potential: The definition applies to females who have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone levels \>40 mIU/mL (for US only: and estradiol \<20 pg/mL) or have had surgical bilateral oophorectomy (with or without hysterectomy) at least 6 weeks prior to starting treatment.
• In the case of oophorectomy alone, only when the reproductive status of the patient has been confirmed by follow-up hormone level assessment is she considered not of childbearing potential.
• Is a pregnant or nursing (lactating) female, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin laboratory test (\>5 mIU/mL). Serum pregnancy test to be assessed within 7 days prior to study treatment start, or within 14 days (with a confirmatory urine pregnancy test within 7 days prior to study treatment start).
• Is unwilling to or unable to comply with the protocol.
• Cancer-related

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Hospital

Singapore, Singapore, 164119, Singapore

RECRUITING

Related Publications (3)

• Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. doi: 10.1200/JCO.2013.51.4489. Epub 2014 Mar 17.

  PMID: 24637997 BACKGROUND

• Kunos CA, Sill MW, Buekers TE, Walker JL, Schilder JM, Yamada SD, Waggoner SE, Mohiuddin M, Fracasso PM. Low-dose abdominal radiation as a docetaxel chemosensitizer for recurrent epithelial ovarian cancer: a phase I study of the Gynecologic Oncology Group. Gynecol Oncol. 2011 Feb;120(2):224-8. doi: 10.1016/j.ygyno.2010.10.018.

  PMID: 21075438 BACKGROUND

• Ngoi NYL, Heong V, Tang JI, Choo BA, Kumarakulasinghe NB, Lim D, Low M, Lim SE, Lim YW, Leong YH, Tseng M, Tong PSY, Ilancheran A, Low JJH, Ng J, Thian YL, Koh V, Tan DSP. Phase 1 Study of Low-Dose Fractionated Whole Abdominal Radiation Therapy in Combination With Weekly Paclitaxel for Platinum-Resistant Ovarian Cancer (GCGS-01). Int J Radiat Oncol Biol Phys. 2021 Mar 1;109(3):701-711. doi: 10.1016/j.ijrobp.2020.09.059. Epub 2020 Oct 9.

  PMID: 33045316 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Paclitaxel

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• David SP Tan

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David SP Tan

CONTACT

(65) 6772 4661; david_sp_tan@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2015
• First Posted: September 9, 2015
• Study Start: September 1, 2015
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2018
• Last Updated: June 22, 2016

Record last verified: 2016-06

Locations

SG (1)