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

Conditions: 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

Summary: 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.

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.

Eligibility criteria:
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