Acetyl-L-Carnitine Hydrochloride in Preventing Peripheral Neuropathy in Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer Undergoing Chemotherapy

Study Overview
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Brief Summary
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This randomized phase III trial studies how well acetyl-L-carnitine hydrochloride works compared to a placebo in preventing peripheral neuropathy in patients with recurrent ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer undergoing chemotherapy. Acetyl-L-carnitine hydrochloride may prevent or lessen peripheral neuropathy caused by chemotherapy. It is not yet known whether acetyl-L-carnitine hydrochloride is more effective compared to a placebo in preventing peripheral neuropathy caused by chemotherapy.

Detailed Description
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PRIMARY OBJECTIVES: I. Evaluate the therapeutic efficacy of acetyl-L-carnitine hydrochloride (ALC) in preventing chemotherapy-induced peripheral neuropathy (CIPN) in patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer. SECONDARY OBJECTIVES: I. Evaluate the effect of ALC on chemotherapy-induced fatigue based upon the Functional Assessment of Cancer Therapy (FACT)-Fatigue scale. II. Evaluate the effect of ALC on sensory peripheral neuropathy as measured with the first 4 items of the FACT/Gynecologic Oncology Group (GOG)-Neurotoxicity (Ntx) subscale (FACT/GOG-Ntx_4 subscale). III. Evaluate the effect of ALC on the health-related quality of life as measured by the FACT-Ovarian (O) trial outcome index (TOI). OUTLINE: This is a multicenter study. Patients are stratified according to planned dosage of paclitaxel (< 150 mg/m^2 vs ≥ 150 mg/m^2), and age (< 60 years of age vs ≥ 6 years of age). Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive acetyl-L-carnitine hydrochloride (ALC) orally (PO) twice daily (BID) on days 1-21 (during chemotherapy treatment). ARM II: Patients receive placebo PO BID on days 1-21 (during chemotherapy treatment) (maximum of 8 courses). In both arms, treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients also complete questionnaires comprising the Functional Assessment of Cancer Therapy (FACT)-Fatigue scale, the FACT-Gynecologic Oncology Group Neurotoxicity subscale (FACT/GOG-Ntx_4 subscale), and the FACT-Ovarian trial outcome index (FACT-O TOI) at baseline, prior to courses 3 and 5, within 4 weeks after completion of treatment, and then at 3 months after completion of treatment.

Official Title
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A Randomized, Double-Blinded, Placebo Controlled Phase III Trial Using Acetyl-L-Carnitine(ALC)(NSC# 747431) for the Prevention of Chemotherapy-Induced Peripheral Neuropathy in Patients With Recurrent Ovarian, Primary Peritoneal or Fallopian Tube Cancer

Conditions
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Fatigue, Malignant Ovarian Mixed Epithelial Tumor, Neuropathy, Neurotoxicity Syndrome, Ovarian Brenner Tumor, Ovarian Clear Cell Cystadenocarcinoma, Ovarian Endometrioid Adenocarcinoma, Ovarian Mucinous Cystadenocarcinoma, Ovarian Serous Cystadenocarcinoma, Pain, Recurrent Fallopian Tube Carcinoma, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma

Intervention / Treatment
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* Dietary Supplement: Acetyl-L-Carnitine Hydrochloride
* Other: Placebo
* Other: Questionnaire Administration
* Other: Quality-of-Life Assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologic diagnosis of epithelial ovarian carcinoma, peritoneal primary or fallopian tube carcinoma, which is now recurrent Patients with the following histologic epithelial cell types are eligible: serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner tumor, or adenocarcinoma not otherwise specified (N.O.S.) All patients must have had a treatment-free interval without clinical evidence of progressive disease of at least 6 months from completion of front-line chemotherapy (both platinum and taxane); front-line therapy may have included a biologic agent (i.e., bevacizumab) Front-line treatment may include maintenance therapy following complete clinical or pathological response; however, maintenance cytotoxic chemotherapy must be discontinued for a minimum of 6 months prior to documentation of recurrent disease; patients receiving maintenance biological therapy or hormonal therapy are ELIGIBLE provided their recurrence is documented more than 6 months from primary cytotoxic chemotherapy completion (includes maintenance chemotherapy) AND a minimum 4 weeks has elapsed since their last infusion of biological therapy Patients receiving hormonal therapy for biochemical or non-measurable recurrence disease are ELIGIBLE provided their recurrence is documented more than 6 months following the completion of primary cytotoxic chemotherapy; a minimum of 4 weeks must have expired since their last exposure to hormonal therapy The complete response to front-line chemotherapy must have included a negative physical exam, normalization of CA125 if elevated at baseline, and negative radiographic assessment of disease, if obtained Patients who have undergone reassessment laparotomy or laparoscopy following primary therapy are eligible for this study as long as they demonstrated a pathologic complete response based on the surgical assessment (i.e. all obtained specimens were histologically negative for disease) Patients with a past history of primary endometrial cancer within the last five years are excluded unless all of the following conditions are met: Stage not greater than IB No more than superficial myometrial invasion, without vascular or lymphatic invasion No poorly differentiated subtypes, including papillary serous, clear cell, or other International Federation of Gynecology and Obstetrics (FIGO) grade 3 lesions Patients must be expected to receive a minimum of 2 cycles of paclitaxel and a platinating agent for their recurrent disease; Addition of other drugs such as bevacizumab is acceptable as long as these additional drugs are not typically associated with peripheral neuropathy The initial, planned infusion duration of each dose of paclitaxel must be 3 hours or less Patients must start the study with a GOG performance status of 2 or less Serum creatinine ≤ 2.5 mg/dL Neuropathy (sensory and motor) less than or equal to the National Cancer Institute (NCI) CTCAE v4.0 grade 1 No patients with a history of seizure activity No patients who are unable to swallow oral medications Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last five years No patients of childbearing potential not practicing adequate contraception No patients who are pregnant or nursing No patients who are known to have diabetes No patients with known allergies to ALC (acetyl-L-carnitine hydrochloride) Patients are excluded if their previous cancer treatment contraindicates this protocol therapy No patients who have received more than one previous regimen of chemotherapy (maintenance is not considered a second regimen) No patients receiving concurrent immunotherapy or radiotherapy No patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis No patients who are currently receiving or have received warfarin or acenocoumarol within the past 7 days No patients taking > 100 units of racemic vitamin E (or > 50 units of ααα-tocopherol) daily within 5 days of starting study therapy No patients taking other medications (Rx, OTC, or dietary supplements) to prevent or treat neuropathy within 5 days of starting study treatment; such products include: Gabapentin (Neurontin ®) Pregabalin (Lyrica ®) Duloxetine (Cymbalta ®) Alpha-lipoic acid Note that tricyclic antidepressants or selective serotonin/norepinephrine-selective reuptake inhibitors prescribed for the treatment of mood disorders are allowed

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (acetyl-L-carnitine hydrochloride)<br>Patients receive ALC PO BID on days 1-21 (during chemotherapy treatment). | Dietary Supplement: Acetyl-L-Carnitine Hydrochloride<br>* Given orally<br>* Other names: Acetylcarnitine L-form HCl;Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;|
| Placebo Comparator: Arm II (placebo)<br>Patients receive placebo PO BID on days 1-21 (during chemotherapy treatment) (maximum of 8 courses). | Other: Placebo<br>* Given orally<br>* Other names: PLCB;Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chemotherapy-related peripheral neuropathy as measured with Functional Assessment of Cancer Therapy (FACT)/GOG-Ntx subscale |  | Up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chemotherapy-related fatigue as measured with FACT-Fatigue |  | Up to 3 months | 
| Patient-reported sensory peripheral neuropathy, as measured by the FACT/GOG-Ntx v4 subscale |  | Up to 3 months | 
| Quality of life, as measured by the FACT-O TOI | Tested at significance level of 5%. | Up to 3 months |